Newsgroup: it.scienza.medicina
Titolo: [%] EGF in saliva e urina

L'urinoterapia (una delle più contestate tra le pratiche alternative)
potrebbe avere qualche fondamento scientifico?  Parrebbe di sì, come
si evince dalle referenze che vi riporto qua in fondo.
Fate attenzione che, in base a queste evidenze, bere urina provocherebbe
l'inibizione della secrezione gastrica, e quindi in una persona normale
darebbe certamente luogo a problemi digestivi (e non soltanto a quelli).
Per questo e altri motivi, è opportuno NON bere urina.  Rimane aperta
la possibilità che l'impiego della propria urina (qualora si sia certi di
non avere infezioni urinarie) per sciacquarsi bocca e denti (come facevano
gli antichi Celtiberi) non risulti necessariamente dannoso e possa anzi,
in qualche caso, risultare utile.  Ma mancano le sperimentazioni cliniche
che lo comprovino, quindi tutto questo rimane a livello di pura ipotesi
speculativa.  In altri termini: per ora, meglio evitare anche questo.
Comunque, queste evidenze devono farci riflettere sul fatto che in ambito
medico non si dovrebbe scartare a priori nessuna eventualità.  E` vero che
gli alternativi non hanno una mentalità scientifica, ma questo non implica
necessariamente che le loro pratiche non abbiano alcuna validità terapeutica,
come del resto scritto da Grmek nel suo libretto e da me riportato in questo
gruppo nel primo messaggio del thread "Ma la medicina che scienza e`?".
In ultimo, da quanto riportato si può trarre la conclusione che probabilmente
nel prossimo futuro saranno disponibili preparazioni farmaceutiche a base
di fattori di crescita (come appunto l'EGF), in grado di avere un'azione
anti-ulcera milioni di volte superiore a quella della cimetidina [9].
Buona lettura degli abstracts.
  -= Ginzo =-
  (0) Nippon Naibunpi Gakkai Zasshi 1983 Oct 20;59(10):1587-96
 [Human epidermal growth factor(urogastrone) in human fluids detected
 by radioreceptor assay]. [Article in Japanese]
 Nakamura K, Imai Y, Matuzaki F
  Epidermal growth factor (EGF)/urogastrone is a polypeptide hormone that
 stimulates growth of a variety of tissues and inhibits gastric acid
 secretion. Although it was originally isolated from male mouse submaxillary
 glands, EGF/urogastrone has recently been isolated from human urine.
 We detected EGF-like activity in human urine, milk and saliva by
 radioreceptor assay using the male mouse hepatic microsomal fraction
 as a receptor preparation and mouse EGF as reference standard. On Sephadex
 G-50 gel chromatography, major EGF-like activity (RRA-EGF) in human urine,
 milk and saliva was eluted near the portion where standard mouse EGF was
 eluted (Kav = 0.5, MW approximately equal to 6000). Isoelectric focusing
 revealed that isoelectric point of major RRA-EGF was 4.45 with minor
 heterogeneity. Twenty-four hour urinary excretion of RRA-EGF in adult males
 and females with normal renal function was 88.8 +/- 4.0 and 65.2 +/- 7.9
 (mean +/- SE) microgram/total volume or 141 +/- 7.2 and 96.5 ng/mg of
 creatinine, respectively. There was no apparent diurnal rhythm in urinary
 RRA-EGF excretion. A series of 24 h urine collection over 5 days from adults
 showed relatively small variations. Urinary levels of EGF per mg creatinine
 in normal children were significantly higher than those in normal males or
 females. There was a reverse correlation between serum creatinine levels
 and urinary EGF levels per creatinine. The concentration of RRA-EGF in human
 milk collected 7 days after starting breast feeding was 81 +/- 11 ng/ml.
 The salivary RRA-EGF concentration was 6.5 +/- 1.0 and 6.9 +/- 0.3
 in normal adult males and females, respectively.
 PMID: 6607183, UI: 84109073
  (1) Life Sci 1987 Jun 29;40(26):2489-94
 Size heterogeneity of epidermal growth factor in human body fluids.
 Pesonen K, Viinikka L, Koskimies A, Banks AR, Nicolson M, Perheentupa J
  We measured the concentration of immunoreactive (IR) hEGF in various body
 fluids by radioimmunoassay (RIA) and evaluated its size heterogeneity by
 size exclusion high performance liquid chromatography combined with RIA or
 with time-resolved immunofluorometric assay (TR-IFMA). Mean concentration
 was 80 ng/ml in urine, 65 ng/ml in milk, 50 ng/ml in seminal plasma,
 25 ng/ml in armpit sweat, 1 ng/ml in breast sweat, 0.3 ng/ml in third-
 trimester amniotic fluid, 3 ng/ml in saliva, 1.5 ng/ml in tears and
 0.3 ng/ml in gastric juice. All the fluids except armpit sweat and gastric
 juice contained two to five molecular sizes of IR-hEGF. As well as the
 6200-dalton (6.2 kDa) hEGF we found at least four other different molecular
 sizes with approximate weights of greater than or equal to 300, 150, 70 and
 20 kDa. The authentic 6.2 kDa form made up greater than 90% of the total
 IR-hEGF in all except the amniotic fluid where its proportion was 71%,
 and the seminal plasma where the proportion could not be determined.
 PMID: 3496510, UI: 87256703
  (2) J Pharmacobiodyn 1988 Mar;11(3):146-51
 Radioimmunoassay of human epidermal growth factor--hEGF levels
 in human body fluids.
 Hayashi T, Sakamoto S
 Central Research Laboratories, Wakunaga Pharmaceutical Co., Ltd.,
 Hiroshima, Japan.
  By immunizing rabbits with purified human epidermal growth factor (hEGF),
 which was synthesized by Escherichia coli constructed by a genetic
 engineering technique, high titer antiserum for hEGF was obtained.
 The antiserum has an excellent specificity to hEGFs (hEGF, hEGF [1-51],
 hEGF [1-47] and [Leu21] hEGF) and has almost no cross-reactivity with
 other biological peptides, such as mouse EGF and human platelet derived
 growth factor. Using radioiodinated hEGF, a radioimmunoassay (RIA)
 for hEGF was established by a double antibody-polyethylene glycol method.
 As little as 10 pg/tube of hEGF was successfully determined by the present
 RIA methods. The intra- and inter-assay coefficients of variation for
 hEGF in human plasma or serum were 2.4-4.9% and 3.7-6.2%, respectively.
 The hEGF levels in human body fluids determined by the present
 method were as follows: urine (11-100 ng/ml), serum (1.0-1.8 ng/ml),
 plasma (0.2-0.8 ng/ml), sperm (17-47 ng/ml), saliva (0.9-3.0 ng/ml)
 and tears (9.5-27 ng/ml).
 PMID: 3261789, UI: 88316595
  (3) J Clin Gastroenterol 1988;10 Suppl 1:S146-51
 Role of epidermal growth factor in gastroduodenal mucosal protection.
 Skov Olsen P
 Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen, Denmark.
  Epidermal growth factor (EGF) is a polypeptide produced in the
 submandibular glands, Brunner's glands, and the kidneys. The peptide is
 secreted in an exocrine fashion into saliva, duodenal juice, and urine.
 EGF stimulates cellular growth and differentiation and inhibits gastric
 acid secretion. Removal of the submandibular glands decreases the amount
 of EGF in saliva and gastric juice and subsequently the synthesis of DNA
 in the gastric mucosa is reduced as well as its resistance to bile-salt-
 induced gastric lesions. Intragastric instillation of EGF can prevent
 gastric ulcerations induced by aspirin as well as cysteamine in rats.
 EGF also accelerates the healing of chronic gastric ulcers induced by
 acetic acid. Cysteamine is a duodenal ulcerogen in rats. After cysteamine
 administration, the secretion of EGF from Brunner's glands decreases and
 the glands become depleted of mucus. Intraduodenal instillation of EGF
 can partly prevent formation of cysteamine-induced duodenal ulcers.
 Oral administration of EGF can accelerate healing of chronic duodenal
 ulcers in rats. The beneficial effect of EGF on healing of chronic
 gastroduodenal ulcers is probably due to the delayed effects of EGF such
 as stimulation of RNA and DNA synthesis. The protective effects of EGF are
 probably related to the early actions of the peptide such as activation
 of cell surface proteins and increased glycosaminoglycan synthesis.
 PMID: 3053882, UI: 89035359
  (4) Annu Rev Physiol 1989;51:67-80
 Epidermal growth factor and the kidney.
 Fisher DA, Salido EC, Barajas L
 Department of Pediatrics, University of California, Los Angeles School
 of Medicine 90509.
  Current information indicates that the mammalian kidney is a significant
 site of EGF synthesis, second only to the salivary gland in the rodent
 and probably exceeding most other tissues in the human species. The prepro
 EGF mRNA is localized to the cells of the TALH and the DCT. The EGF mRNA
 transcript in kidney is similar to that in salivary gland; the molecular
 mass of the prepro EGF protein in kidney approximates 130,000 kDa. Several
 EGF peptides are excreted in urine, including 6000-molecular weight peptides
 (composed of EGF 1-53, 1-52, 1-51, and 1-50) and a 30,000-molecular weight
 species with an aminoterminus portion corresponding to amino acids 829-848
 of the prepro molecule. It has been suggested that prepro EGF could be a
 membrane protein since it contains an internal hydrophobic domain (amino
 acids 1039-1058) adjacent to the EGF sequence (amino acids 976-1029).
 The 30,000-molecular weight urinary product appears to represent a protein
 derived from amino acids 829 to approximately 1029 of prepro EGF, adjacent
 (distal) to the hydrophobic domain. Moreover, immunoelectron microscopy
 localizes the EGF immunoreactivity to the apical plasma membrane of the
 TALH and DCT cells. The molecular form of this apically localized, EGF
 immunoreactivity is not yet clear. Proximal, distal, and TALH cells of
 the renal tubules and renal medullary interstitial cells appear to have
 EGF receptors and respond to EGF with increased DNA synthesis and
 mitogenesis. Also, there is a relatively late increase in prepro EGF mRNA
 levels in TALH and DCT cells during the process of renal hypertrophy.
 Limited evidence suggests a role of EGF on tubular function mediated via
 basal EGF receptors. EGF peptides processed intracellularly or by membrane
 localized peptidases appear to be continuously excreted and secreted
 into urine from the apical membrane surface of the TALH and DCT cells.
 This urinary EGF is constantly bathing urinary tract epithelial surfaces
 and could play a role in maintaining surface integrity. A similar role for
 salivary gland EGF in saliva has been proposed for the gastrointestinal
 tract. It also is possible that prepro EGF is anchored in the apical
 membrane, where it could function as a receptor, and a role for renal
 tubular EGF in regulation of membrane transport events has been proposed.
 PMID: 2653200, UI: 89227026
  (5) J Clin Gastroenterol 1991;13 Suppl 1:S88-97
 Epidermal growth factor in protection, repair, and healing of
 gastroduodenal mucosa.
 Konturek JW, Brzozowski T, Konturek SJ
 Institute of Physiology, Academy of Medicine, Krakow, Poland.
  Gastrointestinal mucosa is one of the most rapidly proliferating tissues
 in the body and the alteration in the balance between cell regeneration
 and cell loss may lead to mucosal lesions and ulcerations. Mucosal growth
 is under the influence of various growth factors, among which epidermal
 growth factor (EGF) and polyamines seem to play a crucial role.
 EGF is produced in large quantities in salivary and pancreatic glands
 and secreted mainly into the gut lumen and partly released into the
 bloodstream from where it is cleared by the kidneys and excreted into
 the urine as urogastrone. The physiological role of EGF is still under
 active investigations but it appears that EGF may be required for the
 maintenance of mucosal integrity and healing of mucosal defects due to its
 accumulation in the lesion area and local stimulation of healing processes.
 The mechanism of protective and ulcer healing effects of EGF involves
 the activation of ornithine decarboxylase (ODC), the key enzyme in the
 biosynthesis of polyamines, which play a crucial role in the growth-
 promoting action of EGF. Substances that affect the generation and/or
 catabolism of polyamines affect the gastroprotective and ulcer healing
 effect of EGF but not that of exogenous polyamines. Mucosal generation
 of protective prostaglandins appears to be essential mainly for the
 gastro-protective effects of EGF but seem to be of little importance in
 the healing effects of EGF on acute and chronic gastroduodenal ulcerations.
 PMID: 1940203, UI: 92043476
  (6) Acta Otolaryngol Suppl 1993;500:126-30
 Kinetics of epidermal growth factor in saliva.
 Ino M, Ushiro K, Ino C, Yamashita T, Kumazawa T
 Department of Otorhinolaryngology, Kansai Medical University, Osaka, Japan.
  Human epidermal growth factor (hEGF) stimulates the growth and
 differentiation of various tissues. We measured EGF levels in saliva
 (n = 128), urine (n = 94), and serum (n = 99) with radioimmunoassay in order
 to study the kinetics of hEGF in saliva of normal subjects and patients with
 oral disease. Salivary EGF levels showed an apparent diurnal rhythm related
 to the taking of meals. Urinary and serum EGF levels showed no obvious
 diurnal rhythm. There was no significant correlation between salivary and
 urinary EGF levels, nor between salivary and serum EGF levels. Salivary EGF
 levels were significantly lower in the younger group (0-9 years old, 3.06
 +/- 0.32 ng/ml, p < 0.05) than in the elder group (10-79 years old, 4.78
 +/- 3.5 ng/ml), but did not correlate with age in the elder group.
 There was no significant difference between males and females between EGF
 levels in saliva, urine or serum. The relative proportion of EGF levels
 in submandibular gland saliva, parotid saliva, and whole saliva was 1:6:4.
 The positive rate of immunohistochemical EGF showed no significant
 differences between submandibular gland, parotid gland, sublingual gland
 or minor salivary gland. Salivary EGF levels were markedly low in patients
 with oral inflammations (stomatitis aphthosa, or peritonsillar abscess)
 or head and neck tumors (squamous cell carcinoma of the tongue, oral cavity,
 hypopharynx or larynx). These findings may be significant pathophysio-
 logically. Low salivary EGF levels may reduce the capacity of oral mucosal
 defense mechanisms to fight against injury by physiochemical agents.
 PMID: 8452009, UI: 93198615
  (7) J Periodontol 1998 Apr;69(4):479-84
 Elevated salivary EGF levels stimulated by periodontal surgery.
 Oxford GE, Nguyen KH, Alford CE, Tanaka Y, Humphreys-Beher MG
 University of Florida College of Medicine, Department of Oral Biology,
 Gainesville 32610-0434, USA.
  Previous studies have shown epidermal growth factor (EGF) to be involved
 in oral wound healing as well as gastric cytoprotection. EGF functions with
 hormone-like properties to stimulate epithelial cells by binding to the EGF
 receptor which ultimately leads to proliferation via signal transduction
 mechanisms. Salivary glands are a major source of EGF. The purpose of this
 study was to determine if intra-oral wounding by periodontal surgery
 stimulated increased salivary EGF levels. Salivary EGF levels were
 determined for 12 systemically healthy individuals (ages 27 to 70 years old)
 presurgically and postsurgically at 6, 12, 18, 24, 30, 36, and 42 hours
 and 2 and 6 weeks. Three ml of unstimulated whole saliva was obtained at
 each time point to allow immunoassay quantitation. Age and gender matched
 unoperated patients served as controls. Salivary samples were incubated
 with monoclonal and polyclonal EGF antibodies in these "sandwich" enzyme
 immunoassays. Quantitation was obtained by spectrometric analysis at OD
 450 nm after addition of 200 microl of colorimetric substrate. Mean EGF
 levels ranged from 2441 pg/ml presurgically to 3349 pg/ml at 18 hours
 postsurgically and 1207 pg/ml at 6 weeks postsurgically. Repeated measures
 analysis of variance indicated statistically significant differences in
 18 hours postsurgical salivary EGF levels when compared to controls and
 to postsurgical levels from 36 hours forward (P < 0.01). A second smaller
 rise in EGF was detected at 30 hours. These results suggest a transient
 increase in salivary EGF levels in response to intra-oral wounding.
 PMID: 9609379, UI: 98270542
  (8) APMIS Suppl 1999;93:1-42
 Pharmacological effects of epidermal growth factor (EGF) with focus
 on the urinary and gastrointestinal tracts.
 Vinter-Jensen L
 Faculty of Health Sciences, University of Aarhus, Denmark.
  Epidermal growth factor (EGF) belongs to a family of growth factor ligands
 and receptors. At present, five ligands have been recognized which as EGF
 exert their effects via binding to the same EGF receptor. The family has
 three other receptors erbB2, erbB3, and erbB4, which have their own ligands
 (the heregulins). The system is ubiquitously distributed in mammals, and has
 important roles in normal development, and in regenerative and neoplastic
 growth. Mouse and human EGF were discovered in 1962 and 1975 by Stanley
 Cohen and Harry Gregory, respectively, due to EGFs potent systemic effects.
 EGF accelerated eyelid opening in newborn mice and inhibited gastric acid
 secretion in humans. Already in the late thirties, a factor in human urine
 was recognized which prevented or accelerated healing of experimental damage
 in the gastrointestinal tract. This factor appeared to be EGF. Around 1980,
 an effect of commercial interest was described - EGF caused shedding of the
 fleece in sheep. In line with the original observations, several studies
 have examined effects of EGF on developmental processes. Amongst other
 effects, EGF accelerates lung and intestinal maturation before birth and
 in newborn mammals. Due to the possible use of EGF in the wool industry,
 it was mandatory to know more about EGF. Amongst other effects in mature
 sheep and other animals are haemodynamic changes, changes in electrolyte
 homeostasis, and endocrinological changes. In relation to experimental
 damage, the therapeutic potential of systemic EGF has been demonstrated
 in all parts of the gastrointestinal tract, in the kidneys, in the liver
 and in the trachea. EGF has even been tried in humans in gastric ulcer
 healing and in necrotising enterocolitis. Studies on prolonged treatment
 with EGF have first recently appeared. We described effects of 4-5 weeks
 of treatment in Goettingen minipigs and in rats, and two other groups
 described effects in monkeys and in rats. In summary, species differences
 were observed. The species of higher order were most sensitive to treatment
 with EGF. EGF did not consistently change the total body weight despite
 EGF consistently reduced circulating levels of insulin-like growth factor I
 (IGF-I) in Goettingen minipigs as well as in rats. Low circulating levels
 of IGF-I are usually associated with retarded growth. This review mostly
 focuses on the organs which appeared to be most sensitive to EGF, the
 urinary and gastrointestinal tracts including the liver and the pancreas.
 The histopathological changes consisted mainly of epithelial proliferations
 in the gastrointestinal, urinary and respiratory tracts. These findings
 match the knowledge obtained from animals overexpressing the EGF agonist,
 transforming growth factor alpha (TGF alpha), and the mice with a knock out
 of the gene encoding for the EGF receptor. EGF receptor hyperstimulation
 (TGF alpha overexpression) in the context of the whole animal leads to
 epithelial proliferations whereas hypostimulation (EGF receptor knock out)
 leads to epithelial immaturities. In the minipigs, the epithelia of the
 oesophagus, ducts of the pancreas, and the urothelium were hyperplastic,
 the latter two epithelia with accumulation of glycoconjugates. In the rats,
 the epithelial hyperplasias in these tissues and in the small and large
 intestines were without glycoconjugate accumulations. In rats, the mucosal
 proliferations in the intestines resulted in increased mucosal surface area.
 Mesenchymal growth effects were also noted. In the ureters of the minipigs,
 smooth muscle cell hyperplasia and hypertrophia were found. The heart of the
 minipigs was also enlarged, an interesting finding regarding interactions
 between the different parts of the EGF system, as knock out mice of
 the receptors erbB2 and erbB4 die due to maldevelopments in the heart.
 Measurements in blood and serum also revealed consistent changes.
 PMID: 10424202, UI: 99353047
  (9) J Physiol Paris 2000 Mar-Apr;94(2):77-81
 Growth factors in ulcer healing: lessons from recent studies.
 Szabo S, Vincze A
 Pathology Service, VA Medical Center, Long Beach, CA 90822, USA.
  Growth factors such as epidermal growth factor (EGF), basic fibroblast
 growth factor (bFGF), platelet-derived growth factor (PDGF) and more
 recently vascular endothelial growth factor (VEGF) have been used
 extensively to heal experimental gastric, duodenal and colonic ulcers
 in animal models. Encouraging results have been reported in clinical trials
 with EGF and bFGF. Since our laboratory has been involved with the initial
 ulcer healing studies with bFGF, PDGF and VEGF, we summarize here the major
 lessons from these studies and from literature data. These conclusions
 relate to the role of: 1) gastrointestinal (GI) secretion; 2) epithelial
 versus vascular components of the healing; 3) efficacy in the upper and
 lower GI tract; 4) quality of ulcer healing; as well as 5) the endogenous
 origin; and 6) molar potency of growth factors. Namely, among these growth
 factors only EGF inhibits gastric acid and stimulates duodenal bicarbonate
 secretion, while chronic administration of bFGF slightly enhances gastric
 secretion and PDGF has no effect demonstrating that potent ulcer healing
 can be achieved without influencing acid base and mucus secretion.
 This might be related to the fact that these growth factors stimulate
 with varying potency virtually all the cellular elements needed for
 ulcer healing, e.g., epithelial cell proliferation and migration by
 EGF > bFGF > PDGF, fibroblast proliferation by bFGF > PDGF and angiogenesis
 by VEGF > bFGF >> PDGF >> EGF. Conceptually, the most interesting results
 were obtained recently with VEGF which is virtually specific for
 angiogenesis, illustrating that stimulation of vascular factors is
 sufficient for ulcer healing because epithelial cells apparently
 spontaneously proliferate and migrate over a dense granulation tissue
 to complete the healing process. Since these growth factors directly
 stimulate the cell components of ulcer healing, it is probably not
 surprising that they are active in both upper and lower GI tract lesions,
 produce good quality of ulcer healing in comparison with spontaneously
 healed duodenal ulcers which are hypovascular and muscle regeneration
 is not part of natural healing. Contrary to other antiulcer drugs, these
 growth factors are endogenously derived and play a role in the natural
 history of ulcer healing, and since these relatively large peptides
 (18-45 kDa) are active in ng quantities, their molar potency is
 2-7 million times superior to cimetidine-like drugs. Thus growth factors
 are endogenously derived very potent antiulcer drugs which act
 independently of GI secretion, are active in upper and lower GI lesions,
 and since they stimulate virtually all the cells of the healing process,
 they produce an excellent quality of ulcer healing.
 PMID: 10791686, UI: 20250325
----

Ciao, Ginzo  :-)))
posso darti una mia opinione?
Tempo addietro ebbi occasione di rispondere a chi tu sai su questo
argomento.
L'urina contiene, tra tante sostanze "di scarto", anche molecole e complessi
(ormoni e quant'altro) che teoricamente (se recuperati) potrebbero ancora
essere utili all'organismo. Non si può, però, prescindere da una
considerazione: se l'organismo li ha eliminati è probabilmente perchè erano
in eccedenza o comunque in quel momento inutili.
Bere urina per recuperarli (e tu nella tua prima frase ventili la
possibilità che l'urinoterapia possa essere "promossa" a metodica
terapeutica) significherebbe compiere un'azione che deroga dalla
"naturalità" seguita dall'organismo.
Inoltre: quand'anche fosse auspicabile recuperare queste sostanze,
occorrerebbe comunque "isolarle" dal contesto "urina" dato che la sua
assunzione tout court porterebbe al reingresso nell'organismo anche di tutto
ciò che di tossico era stato eliminato.
In quella vecchia risposta mi trovai a dire:
"anche nei secchioni dell'immondizia trovo quarti di pollo, avanzi di
spaghetti, mele marce e simili. Questo non significa che io debba frugare
nei secchioni per recuperare quanto di commestibile ancora vi si trova.
Inoltre se per recuperare queste poche sostanze ancora edibili fossi
costretto ad ingurgitare anche cartoni, buste di plastica, escrementi ed
altro.....".
Ho comunque afferrato il senso del tuo discorso: nelle urine indubbiamente
esistono in una certa concentrazione sostanze ancora utili all'organismo...
:-)))))
Posso pregarti di una cortesia?
Potresti (quando il post diviene particolarmente lungo) dividerlo in più
parti di minore peso? Si ottiene una migliore leggibilità ed è più semplice
il quoting  :-)))
Con stima
Docpocket

[...]
Nonostante tutte le successive precisazioni del caso, direi comunque che
la tua precedente affermazione č... poco felice.
Tra l'individuare nell'urina sostanze potenzialmente utili e bere urina
a scopo terapeutico c'e' un oceano (non dico di cosa... :-) )
Ed infatti non mi risulta che agli infartuati in fase acuta o ai
pazienti con fenomeni trombotici si suggerisca di bere urina, sebbene
questa contenga urochinasi, un potentissimo farmaco trombolitico
(abitualmente utilizzato in preparazioni piů da "gabinetto medico" che
da "gabinetto" tout cour).
Noto a latere che le sostanze potenzialmente o attualmente utili ed
efficaci sono contenute nelle urine in concentrazioni risibili, tant'e'
che, per essere estratte, richiedono il trattamento di MIGLIAIA di litri
di escreto renale, generosamente fornite dalle caserme dell'Esercito
Italiano.
        ___
 /\/\/\/ _/
/     / /_
\/\/\/\__/ -Doctor Diabolicus-
 
E-mail:   
d...@mclink.it
URL   :   
http://web.tiscalinet.it/Scienza_e_Medicina
 
ICQ   :   #69417855
Fido  :   2:335/392.101

 il quoting  :-)))
Hai ragione, ma quelli che ho riportato sono studi molto seri e importanti
sui fattori di crescita (EGF e VEGF sono fra le sostanze più interessanti
che si possano impiegare in terapia), quindi mi sono lasciato prendere
la mano e non ho fatto caso alla lunghezza del mio post.  In futuro, se
mi capiterà ancora di dover fare un post con tante citazioni, cercherò
di ridurne le dimensioni o di spezzarlo in più parti.  Grazie dell'appunto.
Saluti.
  -= Ginzo =-

 efficaci sono contenute nelle urine in concentrazioni risibili,
Questo è vero per l'urochinasi, meno per l'EGF.  Infatti se rileggi bene
le (1) e (2) nel mio post iniziale di questo thread, vedrai che la quantità
fisiologica di EGF nella saliva (nota anche la [2] qui in fondo) è di 1,5
(0,9-3) ng/ml, mentre quella contenuta nell'urina è di 80 (11-100) ng/ml.
E la (9) in quel mio post diceva: "these relatively large peptides (18-45
kDa) are active in ng quantities".  Ergo, il contenuto di EGF nell'urina
è già abbastanza alto per poter avere qualche effetto terapeutico, almeno
in teoria.  Poi è ovvio che per poter fare le relative ricerche cliniche
bisogna assicurare ai finanziatori che l'EGF verrà estratto o sintetizzato
e che le ricerche riguarderanno tale sua forma purificata, in modo che
gli eventuali risultati favorevoli possano tradursi per loro in profitti
multimiliardari.  Se invece gli dici che hai intenzione di impiegare l'urina
(purtroppo disponibile gratuitamente), nessuno sarà disposto a cacciar fuori
una lira per finanziare i tuoi studi.  Visto che so che hai una prole ancora
in giovanissima età, ti consiglio di erudirla al riguardo facendogli leggere
l'episodio "Il virus" nel numero 128 (maggio 2000) attualmente in edicola
di "Cattivik".  :-))
In conclusione più seria, ti consiglio di leggere il recentissimo articolo
storiografico di cui ti riporto l'abstract [3] (che fa notare che bere urina
può provocare: nausea, vomito, mal di testa, palpitazioni, diarrea, febbre).
Saluti.
  -= Ginzo =-
  [1] Thromb Res 1986 Dec 15;44(6):867-73
 Determination of urokinase in the urine of healthy volunteers and patients
 with renal diseases.
 Takada A, Sakakibara K, Nagase M, Shizume K, Takada Y
  A sensitive enzyme immunoassay was developed for the determination
 of urokinase in the plasma and urine. Normal human urine contained
 2.68 +/- 0.36 u/ml of UK. Gel filtration of the mixture of normal urine
 resulted in 2 peaks in the profile, one with molecular weight of 32,000 and
 the other with molecular weight of 22,000. Patients with glomerulonephritis
 had higher UK levels. Kidneys with minimal changes and mild type or with
 the inactive phase of systemic lupus erythematosus (SLE) secreted relatively
 high levels of UK in the urine.
 PMID: 3541283, UI: 87094917
  [2] J Dent Res 1995 Dec;74(12):1826-32
 Saliva and growth factors: the fountain of youth resides in us all.
 Zelles T, Purushotham KR, Macauley SP, Oxford GE, Humphreys-Beher MG
 Department of Oral Biology, Semmelweis University Medical School, Budapest,
 Hungary.
  The predominant focus of research dealing with saliva revolves around the
 role in the maintenance of oral health through a number of physiological
 and biological properties of constituent proteins. An ever-expanding
 literature exists indicating that the salivary glands additionally
 synthesize, and secrete into saliva, a wide range of growth factors.
 Animal studies with epidermal growth factor have provided evidence for
 a role in both oral and systemic health, through the promotion of wound
 healing rates. Thus, the ability to manipulate their rates of synthesis and
 absorption from saliva holds the potential to enhance tissue regeneration
 and homeostasis.
 PMID: 8600176, UI: 96183410
  [3] Am J Nephrol 1999;19(2):111-3
 The medicinal use of urine.
 Horl WH
 Division of Nephrology, Department of Medicine, University of Vienna,
 Austria.
  Oral intake of freshly voided morning urine has been recommended for many
 diseases such as viral or bacterial infections. Symptoms reported during
 the first days of oral intake of urine include nausea, vomiting, headache,
 palpitations, diarrhea or fever. Several substances in the urine are
 believed to be important for oral intake such as urea, uric acid, cytokines,
 hormones or urokinase. Local urine therapies include embrocations,
 compresses for local tumors, whole body bath or foot bath in the urine,
 use of urine as eye drops, ear drops or nose drops and the use of urine
 for wound cleaning.
 PMID: 10213804, UI: 99233439
----

a cacciar fuori una lira per finanziare i tuoi studi.
Secondo me a queste condizioni sarebbe difficile trovare non tanto i
finanziatori, ma i soggetti su cui sperimentare :-)
--


 finanziatori, ma i soggetti su cui sperimentare :-)
Dissento.  Mai porre limiti alla stupidità umana... :-)
Bye,
  -= Ginzo =-

> Epidermal growth factor and the kidney.
Ammettendo che tu abbia ragione, a questo punto sarebbe interessante
interrogarsi sul motivo per cui un fattore di crescita altrimenti
diffuso a livello epiteliale, per favorire i processi riparativi degli
epiteli stessi, si ritrovi in un tessuto che embriologicamente deriva
non dal foglietto ectodermico, non da quello endodermico, ma da quello
mesodermico....


AVVISO per il moderatore:  Questo lunghissimo post contiene le referenze
all'articolo da me già inviato separatamente in questo thread.  Si prega
quindi di non cestinarlo, visto che non è una serie di abstract sconnessi.
REFERENZE:
--- Sull'origine dell'EGF urinario:
  [1] Eur J Appl Physiol 1988;58(1-2):26-31
 The source of urinary epidermal growth factor in humans.
 Callegari C, Laborde NP, Buenaflor G, Nascimento CG, Brasel JA, Fisher DA
 Department of Pediatrics, Harbor UCLA Medical Center, Torrance 90509.
  To clarify the source of human urine EGF, we studied EGF renal clearance
 in 20 healthy, young adult subjects. Immunoreactive EGF was measured hourly
 in EDTA plasma, heparin plasma, serum and urine of 12 males and 8 females
 during a 3 h study period. Plasma and urine creatinine and creatinine
 clearance were measured and calculated hourly. Mean (and SEM) creatinine
 clearance was similar in males and females (118 +/- 12 vs 105 +/- 6 ml/min).
 EGF was not detectable in plasma, whereas relatively high levels were
 measured in serum (2.5 +/- 0.25 vs 1.5 +/- 0.18 ng/ml in males and females
 respectively p less than 0.05). Urine EGF excretion averaged 1641 +/- 233
 ng/h in males and 1507 +/- 191 ng/h in females (p greater than 0.05).
 A significant correlation was observed between urine creatinine and urine
 EGF concentrations in both male (r = 0.98, p less than 0.01) and female
 (r = 0.94, p less than 0.01) subjects. EGF immunoreactivity in urine and
 serum eluted from G-75 sephadex columns similarly to recombinant 6000 Mr
 hEGF. Urine excretion of EGF approximated 1.5 micrograms/h or 25 ng/mg
 creatine. The high concentrations of EGF found in urine in the face of
 non-detectable levels of EGF in plasma favor the hypothesis that EGF
 in urine is derived from kidney synthesis and secretion. The significant
 positive correlation between urine creatinine and urine EGF suggests
 a functional correlation between glomerular filtration and the process
 of tubular EGF excretion.
 PMID: 3264526, UI: 89078378
  [2] J Endocrinol 1993 Nov;139(2):227-34
 Urinary epidermal growth factor is excreted from the rat isolated perfused
 kidney in the absence of plasma.
 Jorgensen PE, Hilchey SD, Nexo E, Poulsen SS, Quilley CP
 Department of Clinical Chemistry, KH University Hospital of Aarhus, Denmark.
  Large amounts of epidermal growth factor (EGF) are excreted in urine and
 the majority of this urinary EGF appears to be of renal origin. EGF is
 synthesized in the kidneys as a membrane-bound 160 kDa precursor, in the
 thick ascending limb of Henle and in the early part of the distal convoluted
 tubule. Very little is known about how EGF is released from cell membranes
 into urine but proteolytic cleavage of the membrane-bound EGF precursor
 seems likely. The purpose of this study was to examine whether plasma
 constituents are necessary for urinary excretion of EGF. In the rat isolated
 kidney perfused at a pressure of 90 mmHg with a modified Krebs-Henseleit
 buffer containing oncotic agents, the quantity of EGF excreted into the
 ureteral effluent was 67% of the amount excreted by the rat kidney in vivo.
 The EGF excreted by the isolated kidney behaved like urinary EGF upon gel
 filtration. Administration of the proteinase inhibitor aprotinin reduced
 urinary EGF excretion from the rat isolated perfused kidney by approximately
 50%. In conclusion, the rat isolated perfused kidney excreted significant
 amounts of urinary EGF without having access to plasma, and EGF excretion
 was reduced by aprotinin. This is further evidence suggesting an intrarenal
 source of urinary EGF and suggests that the EGF precursor in the rat kidney
 is processed by enzyme(s) of renal origin.
 PMID: 7508486, UI: 94141405
--- Aumento sintesi EGF in nefrectomia unilaterale:
  [3] Eur J Clin Invest 1995 Jun;25(6):442-6
 Urinary excretion of epidermal growth factor in living human kidney donors
 and their recipients.
 Jorgensen PE, Kamper AL, Munck O, Strandgaard S, Nexo E
 Department of Clinical Biochemistry, KH University Hospital of Aarhus,
 Denmark.
  Epidermal growth factor (EGF) is a growth-promoting peptide that is
 synthesized in the distal tubules of the kidney and excreted in urine.
 EGF has been suggested to play a role in the repair after renal tissue
 damage, as well as in compensatory growth of the remaining kidney after
 uninephrectomy. The present study examined the urinary EGF excretion after
 uninephrectomy and transplantation among relatives. The urinary EGF
 excretion rate and the glomerular filtration rate (GFR) were followed
 for 26-54 days in 16 healthy kidney donors and nine recipients. After
 uninephrectomy the median urinary EGF excretion rate in the donors was not
 50% of the pre-operative value, but around 65% (95% confidence limits
 of the median on the fifth post-operative day: 59-72%). This suggests
 that there is a compensatory increase in the EGF excretion rate from the
 remaining kidney of around 30% after uninephrectomy. A similar compensatory
 increase was demonstrated for GFR, indicating that the compensatory changes
 in EGF excretion rate and GFR might be correlated. In the transplanted
 kidneys, GFR was consistently around 15% lower and EGF excretion rate
 around 40% lower than in the corresponding kidneys remaining in the donors.
 This might reflect ischaemic and drug-induced damage of the transplanted
 kidneys. The present study demonstrated a compensatory increase of around
 30% in urinary EGF excretion from the remaining kidney after uninephrectomy
 in healthy humans. Whether EGF plays a role in the adaptive processes in
 the remaining kidney or whether changes in EGF excretion are merely of a
 secondary nature is still uncertain.
 PMID: 7656924, UI: 95385735
  [4] Regul Pept 1997 Oct 31;72(2-3):179-86
 Urinary excretion of epidermal growth factor and Tamm-Horsfall protein
 in three rat models with increased renal excretion of urine.
 Thulesen J, Jorgensen PE, Torffvit O, Nexo E, Poulsen SS
 Institute of Medical Anatomy, Department B, University of Copenhagen,
 Denmark. 
J.Thu...@mai.ku.dk
  Epidermal growth factor (EGF) and Tamm-Horsfall protein (THP) are
 synthesized in the kidneys by the distal tubular cells and excreted into
 urine. The urinary excretion of these peptides has been suggested as a
 potential index for distal tubular function. The urinary excretion rates
 of EGF and THP were examined in three groups of rats with increased renal
 excretion of urine: uninephrectomy, non-osmotic polyuria and diabetic
 osmotic polyuria. Twenty-four hour urine samples were obtained after 7, 14
 and 21 days. The urinary volume per kidney was doubled in uninephrectomy
 when compared to controls. There was a seven-fold increase in urinary volume
 in rats with non-osmotic polyuria and diabetic osmotic polyuria, as compared
 to controls. Uninephrectomy, non-osmotic polyuria and diabetes all affected
 the urinary excretion of EGF and THP differently. The EGF excretion in
 uninephrectomized rats was 60-80% of that of the controls, whereas THP
 excretion was unchanged, indicating that EGF excretion varied with renal
 tissue mass. Non-osmotic polyuria caused a five-fold increase in THP
 excretion but no change in EGF excretion. THP excretion in the diabetic
 rats was increased three-fold after 21 days when compared to controls,
 whereas EGF excretion was decreased when expressed per kidney weight.
 Immunohistochemistry demonstrated that EGF and THP were colocalized in the
 thick ascending limbs of Henle's loops and distal tubules in all five groups
 of rats. In conclusion, the EGF excretion appears to follow renal tissue
 mass and seems independent of urinary volume, whereas THP excretion is
 dependent mainly on urinary volume. This has implications for the use of EGF
 and/or THP excretion rates as an indicator for distal tubular function.
 PMID: 9652978, UI: 98139377
--- Diminuzione secrezione EGF con l'età:
  [5] Ann Clin Lab Sci 1997 Mar-Apr;27(2):116-22
 Aging and urinary excretion of epidermal growth factor.
 Chou JS, Reiser IW, Porush JG
 Division of Nephrology and Hypertension, Brookdale University Hospital and
 Medical Center, Brooklyn, NY 11212, USA.
  The aging process in man leads to some loss of kidney mass and function.
 The kidney produces epidermal growth factor (EGF), a polypeptide involved
 in the repairing process of epithelial cells. Human urine contains high
 concentrations of EGF, derived from its production in the kidney. It is
 not known if aging alters urinary EGF production in humans. This study
 investigates the possibility of decreased urinary EGF in elderly people.
 Urine samples were collected from 70 healthy subjects of various ages and
 measured for EGF by the technique of radioimmunoassay. The studied urine
 samples were divided into five age groups (3 to 10, 11 to 20, 21 to 60,
 61 to 70, and 71 to 80 years). Urinary EGF (corrected for the urine
 creatinine concentration and measured as ng per mg creatinine) was highest
 in the two youngest groups, 78.5 +/- 14.3 and 76.2 +/- 18.8 (mean +/-
 standard error of the mean), respectively, and decreased with age so that
 the lowest urinary EGF was observed in the oldest group (27.0 +/- 8.8 ng
 per mg creatinine). In addition, a significant inverse relationship exists
 between urinary EGFD in all 79 subjects and their respective age (P < 0.001).
 These findings show that normal values of urinary EGF should take age into
 account. The reduced production of EGF by the kidney in the elderly may have
 functional significance in retarding the repair process in the kidney.
 PMID: 9098510, UI: 97253059
--- Ruolo dell'EGF nella nefrogenesi:
  [6] Microsc Res Tech 1997 Nov 1;39(3):261-84
 Diverse aspects of metanephric development.
 Wallner EI, Carone FA, Abrahamson DR, Kumar A, Kanwar YS
 Department of Medicine, Northwestern University Medical School, Chicago,
 Illinois 60611, USA.
  Mammalian nephrogenesis constitutes a series of complex developmental
 processes in which there is a differentiation and rapid proliferation of
 pluripotent cells leading to the formation of a defined sculpted tissue
 mass, and this is followed by a continuum of cell replication and terminal
 differentiation. Metanephrogenesis ensues with the intercalation of
 epithelial ureteric bud into loosely organized metanephric mesenchyme.
 Such an interaction is reciprocal, such that the intercalating ureteric
 bud induces the conversion of metanephric mesenchyme into an epithelial
 phenotype, while the mesenchyme stimulates the iterations of the ureteric
 bud. The induced mesenchyme then undergoes a series of developmental stages
 to form a mature glomerulus and tubular segments of the kidney. Coincidental
 with the formation of these nephric elements, the developing kidney is
 vascularized by the process of vasculogenesis and angiogenesis. Thus,
 the process of metanephric development is quite complex, and it involves a
 diverse group of molecules who's biological activities are inter-linked with
 one another and they regulate, in a concerted manner, the differentiation
 and maturation of the mammalian kidney. This diverse group of molecules
 include extracellular matrix (ECM) proteins and their receptors, ECM-
 degrading enzymes and their inhibitors, growth factors and their receptors,
 proto-oncogenes and transcription factors. A large body of literature data
 are available, which suggest a critical role of these molecules in
 metanephric development, and this review summarizes the recent developments
 that relate to metanephrogenesis.
 PMID: 9372499, UI: 98039768
  [7] Ann Med 1997 Dec;29(6):531-4
 Epidermal growth factor receptor in mice and men --
 any applications to clinical practice?
 Miettinen PJ
 Department of Pathology, University of Helsinki and Hospital for Children
 and Adolescents, Finland.
 
paivi.m...@helsinki.fi
  The epidermal growth factor receptor (EGF-R) is perhaps the best studied
 member of tyrosine kinase receptors. Its inactivation by homologous
 recombination results in three different phenotypes ranging from
 peri-implantation lethality to postnatal lethality. The mildest form
 of EGF-R inactivation leads to epithelial immaturity and postnatal death
 due to respiratory failure and necrotizing enterocolitis-like lesions in
 the intestine. The defects seen in this 'postnatal lethality phenotype'
 manifest in the classical EGF-responsive organs (skin, intestine) and
 organs undergoing branching morphogenesis during development (lung, kidney,
 mammary gland, pancreas and prostate), and thus accord with the concept
 of EGF family members being important epithelial mitogens. The respiratory
 failure of the EGF-R (-/-) mice results from impaired branching of the
 alveolar tree and leads to decreased surface for gas exchange. Overall,
 the lung phenotype bears similarity to respiratory distress syndrome and
 bronchopulmonary dysplasia--the most common complications of prematurity
 in humans. Intestinal changes seen in the EGF-R (-/-) mice vary in severity,
 the end-point being severe mucosal lesions and necroses. These findings
 resemble those seen in necrotizing enterocolitis of premature babies,
 a serious intestinal problem in the neonate. Although deficient EGF-R
 function is not the reason for these prematurity-associated diseases it may
 nevertheless exacerbate them. Potential usage of EGF transforming growth
 factor-alpha in clinical work is discussed.
 PMID: 9562519, UI: 98221011
  [8] Biofactors 1998;7(4):323-35
 Mitogenic effects of EGF/TGF alpha and immunolocalization of cognate
 receptors in human fetal kidneys.
 Chailler P, Briere N
 Departement d'Anatomie et de Biologie Cellulaire, Faculte de Medecine,
 Universite de Sherbrooke, Quebec, Canada.
  The involvement of epidermal growth factor (EGF) and homologous
 transforming growth factor (TGF) in human kidney development was studied by
 analyzing their effects on the regulation of DNA synthesis in organ culture
 and by localizing their cognate receptors. Both peptides significantly
 increased 3H-thymidine incorporation when added at 10-100 ng/ml, but not at
 1-5 ng/ml. Furthermore, addition of an anti-EGF receptor antibody not only
 reduced the effect of exogenous EGF (100 ng/ml) on DNA synthesis but
 decreased basal 3H-thymidine incorporation. These results indicate that
 EGF/TGF alpha are both mitogenic in vitro and further suggest that human
 fetal kidneys release an endogenous EGF-related substance masking the
 effects of low amounts of growth factors added to culture medium.
 Radioautographic analyses show that EGF (100 ng/ml) increased DNA synthesis
 in poorly-differentiated cells of the nephrogenic zone, particularly in
 subcapsular mesenchyme and peritubular cells; although less responsive,
 epithelial cells in early nephric tubules represented another target of
 EGF action. The pattern of EGF/TGF alpha receptor expression was revealed
 immunohistochemically at different gestational ages and was shown to be
 related to the proliferation status. It was maximal in condensing
 nephrogenic cells, relatively high in newly-induced epithelium and
 cortical branches of ureteric epithelium, low in differentiating nephronic
 cells and nearly absent from renal stroma and medullary collecting ducts.
 Together, our results indicate that the EGF/TGF alpha system is directly
 involved in the regulation of nephrogenic cell proliferation during human
 metanephrogenesis and it is progressively down-regulated after conversion
 of mesenchyme into epithelium.
 PMID: 9666320, UI: 98330729
--- L'EGF contrasta l'apoptosi renale:
  [9] Curr Opin Nephrol Hypertens 1998 Jul;7(4):419-24
 Growth factors and apoptosis in acute renal injury.
 Hammerman MR
 Department of Internal Medicine and Cell Biology and Physiology,
 Washington University School of Medicine, St. Louis, MO, USA.
  The precisely orchestrated pattern of growth factor expression within the
 kidney following acute renal injury indicates that growth factors regulate
 the process of repair. The use of growth factors as therapeutic agents to
 accelerate renal regeneration in this setting stems from this observation.
 In animal models of acute renal injury, administration of epidermal growth
 factor (EGF), insulin-like growth factor I (IGF-I) or hepatocyte growth
 factor (HGF) accelerates restoration of kidney function and normalization
 of histology post-acute renal injury and reduces mortality. IGF-I has been
 safely administered to humans and protects against post-surgical renal
 dysfunction. Renal cellular apoptosis occurs in a predictable pattern during
 recovery from acute ischemic injury. Renal apoptosis is regulated by agents
 both intrinsic and extrinsic to the kidney cell. The protooncogene, B-cell
 lymphoma/leukemia gene product-2 (bcl-2), is an important intrinsic factor.
 The growth factor, EGF, is an important extrinsic regulator. A thorough
 understanding of the control of renal apoptosis during recovery from
 ischemic injury coupled with an increased understanding of the roles that
 growth factors play in this process, is likely to result in the development
 of new therapies to enhance kidney regeneration.
 PMID: 9690042, UI: 98354496
  [10] J Biol Chem 1999 Jun 18;274(25):17612-8
 Epidermal growth factor protects epithelial cells against Fas-induced
 apoptosis. Requirement for Akt activation.
 Gibson S, Tu S, Oyer R, Anderson SM, Johnson GL
 Program in Molecular Signal Transduction, Division of Basic Sciences,
 National Jewish Medical and Research Center, University of Colorado
 Medical School, Denver, Colorado 80206, USA.
  Chemotherapeutic drugs that damage DNA kill tumor cells, in part, by
 inducing the expression of a death receptor such as Fas or its ligand, FasL.
 Here, we demonstrate that epidermal growth factor (EGF) stimulation of
 T47D breast adenocarcinoma and embryonic kidney epithelial (HEK293) cells
 protects these cells from Fas-induced apoptosis. EGF stimulation of
 epithelial cells also inhibited Fas-induced caspase activation and the
 proteolysis of signaling proteins downstream of the EGF receptor, Cbl and
 Akt/protein kinase B (Akt). EGF stimulation of Akt kinase activity blocked
 Fas-induced apoptosis. Expression of activated Akt in MCF-7 breast
 adenocarcinoma cells was sufficient to block Fas-mediated apoptosis.
 Inhibition of EGF-stimulated extracellular signal-regulated kinase (ERK)
 activity did not affect EGF protection from Fas-mediated apoptosis.
 The findings indicate that EGF receptor stimulation of epithelial cells has
 a significant survival function against death receptor-induced apoptosis
 mediated by Akt.
 PMID: 10364198, UI: 99292722
  [11] J Clin Invest 1999 Sep;104(5):541-9
 Inhibition of apoptosis induced by ischemia-reperfusion prevents
 inflammation.
 Daemen MA, van 't Veer C, Denecker G, Heemskerk VH, Wolfs TG, Clauss M,
 Vandenabeele P, Buurman WA
 Department of General Surgery, University of Maastricht, 6200 MD Maastricht,
 The Netherlands.
  Ischemia followed by reperfusion leads to severe organ injury and
 dysfunction. Inflammation is considered to be the most important cause of
 tissue injury in organs subjected to ischemia. The mechanism that triggers
 inflammation and organ injury after ischemia remains to be elucidated,
 although different causes have been postulated. We investigated the role
 of apoptosis in the induction of inflammation and organ damage after renal
 ischemia. Using a murine model, we demonstrate a relationship between
 apoptosis and subsequent inflammation. At the time of reperfusion,
 administration of the antiapoptotic agents IGF-1 and ZVAD-fmk (a caspase
 inactivator) prevented the early onset of not only renal apoptosis, but
 also inflammation and tissue injury. Conversely, when the antiapoptotic
 agents were administered after onset of apoptosis, these protective effects
 were completely abrogated. The presence of apoptosis was directly correlated
 with posttranslational processing of the endothelial monocyte-activating
 polypeptide II (EMAP-II), which may explain apoptosis-induced influx and
 sequestration of leukocytes in the reperfused kidney. These results strongly
 suggest that apoptosis is a crucial event that can initiate reperfusion-
 induced inflammation and subsequent tissue injury. The newly described
 pathophysiological insights provide important opportunities to effectively
 prevent clinical manifestations of reperfusion injury in the kidney, and
 potentially in other organs.
 PMID: 10487768, UI: 99417692
  [12] Kidney Int 1999 Oct;56(4):1299-304
 Cell survival or death in renal tubular epithelium after
 ischemia-reperfusion injury.
 Gobe G, Willgoss D, Hogg N, Schoch E, Endre Z
 Department of Pathology, University of Queensland Medical School, Brisbane,
 Australia. 
g.g...@mailbox.uq.edu.au
  A major contributor to the development and progression of ischemia-
 reperfusion (IR)-induced acute renal failure (ARF) is the loss of
 functioning tubular epithelial cells by means of various cell deletion or
 death processes. Although the term "acute tubular necrosis" is still used
 to describe the pathology of ARF, this is a misnomer because apoptotic cell
 death, as well as necrosis, occurs [1, 2] along with desquamation and loss
 of viable epithelial cells [3]. Apoptosis was first described in renal
 disease in 1987 in an animal model of hydronephrosis [4]. In ARF, with
 reference to only the death processes, the relative contribution of necrosis
 or apoptosis possibly depends on the extent of the initiating events. For
 example, after prolonged total renal ischemia, necrosis or "accidental cell
 death" occurs from the resultant negation of the cell's energy and protein
 levels. In apoptosis, the cells use their own energy processes and proteins
 to die, and often the initiating ischemia is more mild [5]. Finally, despite
 prolonged ischemia, within the heterogeneous renal cell populations there
 are those that are more sensitive to ischemia, such as the proximal straight
 tubule and to some extent the thick ascending limb (TAL) of the loop of
 Henle. It may be hypothesized that these cells tend to undergo necrosis in
 comparison with the less sensitive segments that undergo apoptosis. Because
 apoptosis is gene driven, its identification is important because of the
 possibility of its modulation via molecular controls. However, despite these
 new concepts of ARF, patient death remains high, at approximately 30 to 50%
 of ARF cases. Recovery from ARF depends not only on the replacement or
 regeneration of cells deleted by death, the theme of many recent studies,
 but also on protection of cells from death. Both processes are dependent
 on many of the cellular and molecular controls that have evolved in
 multicellular organisms to manage normal development, differentiation and
 growth processes, but that then become involved in the pathogenesis and
 progression of many renal diseases, including ARF.
 PMID: 10504480, UI: 99436329
  [13] Nephron 2000 Jan;84(1):6-12
 Obstructive nephropathy: lessons from cystic kidney disease.
 Chevalier RL
 Department of Pediatrics, University of Virginia, School of Medicine,
 Charlottesville, VA, USA. 
rl...@virginia.edu
  Obstructive nephropathy is one of the most important causes of renal
 failure in infants and children, while polycystic kidney disease (PKD)
 is a major cause of renal failure in the adult population. This review
 summarizes the evidence that there may be a number of mechanisms common
 to the pathophysiology of both conditions. In animal models of obstructive
 nephropathy and PKD, the renal tubular expression of epidermal growth factor
 is suppressed, and expression of clusterin is increased, both of which
 suggest arrested maturation or dedifferentiation of the tubular cell.
 There is a marked increase in apoptosis of epithelial cells in dilated
 tubules, associated with an increase in apoptotic stimuli. The renin-
 angiotensin system is activated in both obstructive nephropathy and PKD,
 which may contribute to tubular atrophy and interstitial fibrosis, which
 characterize the progression of both conditions. Focal cystic dilatation of
 the tubule is found in obstructive nephropathy, while tubular obstruction
 is present in cystic kidney disease. It is therefore likely that elucidation
 of the effects of mechanical stretch on renal tubular epithelial cells
 will contribute to our understanding of both conditions.
 PMID: 10644902, UI: 20112994
  [14] Am J Pathol 2000 Mar;156(3):889-98
 Heparin-binding EGF-like growth factor is up-regulated in the obstructed
 kidney in a cell- and region-specific manner and acts to inhibit apoptosis.
 Nguyen HT, Bride SH, Badawy AB, Adam RM, Lin J, Orsola A, Guthrie PD,
 Freeman MR, Peters CA
 Urologic Laboratory, Department of Urology, Children's Hospital, Boston,
 MA 02115, USA.
  The expression of certain growth factors in the epidermal growth factor
 (EGF) family is altered in response to renal injury. Recent studies have
 demonstrated that heparin binding EGF-like growth factor (HB-EGF) expression
 may be cytoprotective in response to apoptotic signals. The purpose of this
 study was to investigate the potential role of HB-EGF in the upper urinary
 tract following unilateral ureteral obstruction. We present evidence that:
 i) ureteral obstruction induced cell-specific but transient activation of
 HB-EGF gene expression; ii) HB-EGF expression in renal epithelial cells
 increased under conditions where mechanical deformation, such as that caused
 by hydronephrotic distension, induces apoptosis, but HB-EGF expression did
 not increase in renal pelvis smooth muscle cells under identical conditions;
 and iii) enforced expression of HB-EGF served to protect renal epithelial
 cells from stretch-induced apoptosis. These results suggest a potential
 mechanism by which the kidney protects itself from apoptosis triggered
 by urinary tract obstruction.
 PMID: 10702406, UI: 20169065
--- Effetto nefroprotettivo della somministrazione di EGF:
  [15] Kidney Int 1998 Jul;54(1):38-47
 Obstructive nephropathy in the neonatal rat is attenuated by epidermal
 growth factor.
 Chevalier RL, Goyal S, Wolstenholme JT, Thornhill BA
 Department of Pediatrics, University of Virginia, School of Medicine,
 Charlottesville, USA.
  BACKGROUND: Obstructive nephropathy is a primary cause of renal failure
 in infancy. Chronic unilateral ureteral obstruction (UUO) in the neonatal
 rat results in reduced renal expression of epidermal growth factor (EGF),
 renal tubular epithelial (RTE) cell apoptosis and interstitial fibrosis.
 We wished to determine whether these changes could be prevented by exogenous
 administration of EGF. METHODS: Thirty-three Sprague-Dawley rats underwent
 UUO within the first 48 hours of life, and received daily injections of
 either EGF (0.1 mg/kg/day) or saline (control) for the following seven days,
 after which obstructed and intact opposite kidneys were removed for study.
 These were compared to 11 sham-operated rats that received either no
 injections, EGF injections, or saline injections. Renal cell proliferation
 was determined by proliferating cell nuclear antigen, apoptosis was measured
 by the TUNEL technique, and the distribution of vimentin, clusterin,
 transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth muscle
 actin were determined by immunohistochemistry. Tubular dilation, tubular
 atrophy, and interstitial collagen deposition were quantitated by
 histomorphometry. RESULTS: Compared to controls, EGF treatment increased
 RTE cell proliferation in the obstructed kidney by 76%, decreased apoptosis
 by 80%, and reduced vimentin, clusterin and TGF-beta 1 immunostaining (all
 P < 0.05). EGF treatment reduced tubular dilation by 50%, atrophic tubules
 by 30%, and interstitial fibrosis by 50% (all P < 0.05). There was no
 significant effect of EGF on renal alpha smooth muscle actin distribution.
 There was no effect of saline or EGF injections on kidneys from sham-operated
 rats for any of the parameters studied. CONCLUSIONS: We conclude that EGF
 stimulates RTE cell proliferation and maturation and reduces apoptosis
 in the neonatal rat kidney subjected to chronic UUO. These effects may
 contribute to the reduction in tubular dilation, tubular atrophy, and
 interstitial fibrosis. By preserving renal development, administration
 of EGF attenuates the renal injury resulting from chronic UUO.
 PMID: 9648061, UI: 98311867
  [16] J Urol 1999 Oct;162(4):1532-6
 EGF improves recovery following relief of unilateral ureteral obstruction
 in the neonatal rat.
 Chevalier RL, Goyal S, Thornhill BA
 Department of Pediatrics, University of Virginia, Charlottesville 22908,
 USA.
  PURPOSE: Renal epidermal growth factor (EGF) is suppressed by unilateral
 ureteral obstruction (UUO), and we reported previously that exogenous EGF
 attenuates renal injury due to UUO in the neonatal rat. In this study, we
 wished to determine whether administration of epidermal growth factor (EGF)
 improves long-term renal cellular recovery after relief of obstruction.
 MATERIALS AND METHODS: One ureter of 1 day-old rats was occluded or
 sham-operated, and rats received daily injections of EGF, 0.1 mg./kg.,
 or saline for the following 7 days. Five days following UUO, the obstruction
 was removed. Kidneys were removed 28 days following release of UUO or sham
 operation, and processed for histomorphometry and immunohistochemistry.
 RESULTS: Kidney weight and the number of glomeruli were reduced in the
 postobstructed kidney regardless of administration of EGF. However, EGF
 reduced tubular vimentin by 36% and clusterin expression by 70% (markers
 of tubular injury), and decreased tubular atrophy by 50% in the
 postobstructed kidney compared with saline-treated rats. EGF also reduced
 interstitial alpha-smooth muscle actin and interstitial collagen deposition
 by 50% in the postobstructed kidney. CONCLUSIONS: Short-term administration
 of EGF markedly attenuates both tubular and interstitial injury one month
 following the release of UUO in the neonatal rat. This suggests therapeutic
 potential for targeted delivery of growth factors to optimize recovery
 after release of urinary tract obstruction.
 PMID: 10492250, UI: 99419999
--- L'EGF protegge l'epitelio gastrico:
  [17] J Pharmacol Exp Ther 1999 Feb;288(2):620-6
 Epidermal growth factor protects rat epithelial cells against acid-induced
 damage through the activation of Na+/H+ exchangers.
 Furukawa O, Matsui H, Suzuki N, Okabe S
 Department of Applied Pharmacology, Kyoto Pharmaceutical University,
 Misasagi, Yamashina, Kyoto, 
Japan.f...@mb.kyoto-phu.ac.jp
  We examined the effect of epidermal growth factor (EGF) on acid-induced
 cell damage in rat gastric epithelial cells (RGM1) and investigated the
 mechanisms of this effect. Cells were incubated with EGF for 5, 15, 30,
 and 60 min, and then immersed in an acidified medium (pH 4.0) for 30 min
 to induce cell damage. EGF prevented cell damage in a concentration- and
 time-dependent manner. EGF reduced the effects of the acidified medium on
 the cells, preventing the reduction of intracellular pH. Replacement of
 Na+ with K+ in the acidified medium canceled the effect of EGF. Indomethacin
 and W-7 (a Ca-calmodulin inhibitor) did not alter the protective effect
 of EGF. In contrast, genistein (a tyrosine kinase inhibitor), amiloride
 (a Na+/H+ exchangers I and II inhibitor), and wortmannin (a phosphatidyl-
 inositol 3-kinase inhibitor) significantly decreased the effect of EGF.
 Expression of Na+/H+ exchangers type I and type II was confirmed by reverse
 transcription-polymerase chain reaction. Our results demonstrate that EGF
 prevents acid-induced cell damage, most likely through the activation of
 a Na+/H+ exchanger II via phosphatidylinositol 3-kinase.
 PMID: 9918567, UI: 99117431
--- L'EGF nel diabete:
  [18] Proc Natl Acad Sci U S A 1989 Oct;86(19):7644-8
 Epidermal growth factor deficiency associated with diabetes mellitus.
 Kasayama S, Ohba Y, Oka T
 Laboratory of Molecular and Cellular Biology, National Institute of Diabetes
 and Digestive and Kidney Diseases, Bethesda, MD 20892.
  The production of epidermal growth factor (EGF) in the submandibular gland
 and its circulating level were studied in diabetic mice. In genetically
 diabetic (C57BL/KsJ db/db) mice, EGF concentrations in the submandibular
 gland and plasma were reduced to 13% and 30% of the control levels,
 respectively. In streptozotocin-treated diabetic mice, they were reduced
 to 18% and 20% of controls, respectively, 5 weeks after the drug injection.
 Furthermore, levels of submandibular prepro-EGF mRNA in these diabetic mice
 were decreased almost in parallel with the glandular EGF concentrations,
 while there was no change in the levels of submandibular beta-actin mRNA
 and kidney prepro-EGF mRNA. In addition, histological examination of the
 submandibular glands indicated that the size of the granular convoluted
 tubules, which produce EGF, was substantially reduced in the diabetic mice.
 Insulin administration to streptozotocin-treated mice almost completely
 reversed the decrease in EGF content in the submandibular gland,
 substantially elevated the level of the glandular prepro-EGF mRNA and
 plasma EGF concentration, and increased the size of the granular convoluted
 tubules in the gland. These results indicate that EGF deficiency occurs
 in diabetes mellitus and that insulin may be important in maintaining
 the normal level of EGF in the submandibular gland and plasma.
 PMID: 2477846, UI: 90017535
  [19] Life Sci 1990;47(8):679-85
 Epidermal growth factor in serum, urine, submandibular glands and kidneys
 of diabetic mice.
 Hwang DL, Lev-Ran A
 Department of Diabetes, City of Hope National Medical Center Duarte,
 California.
  Levels of epidermal growth factor (EGF) in serum were significantly
 decreased in streptozotocin (STZ)-diabetic mice (446 +/- 168 pg/ml after
 1 week and 423 +/- 52 after 4 weeks vs 766 +/- 162 pg/ml in controls, P.002
 and less than .001. respectively) and in genetically diabetic ob/ob mice
 (455 +/- 285 vs 962 +/- 453 pg/ml in nondiabetic ob/+ controls, P.043).
 The urinary excretion of EGF was significantly increased in STZ mice (104
 +/- 53 vs 51 +/- 23 ng/h, P.013) but unchanged in ob/ob mice (33 +/- 9 vs
 45 +/- 16 ng/h, P.134). However, when expressed per mg creatinine it was
 decreased in both cases: in STZ mice to 680 +/- 250 ng/mg at 1 week and
 684 +/- 211 at 4 weeks vs 1250 +/- 303 ng/mg in controls (P less than .01);
 and in the ob/ob mice to 552 +/- 117 vs 1237 +/- 300 ng/mg in ob/+ controls
 (P less than .01). EGF content of the submandibular glands of STZ mice
 remained unchanged at 1 week (13.1 +/- 2.9 vs 11.0 +/- 1.8 micrograms/mg
 protein, P.170) but dropped by 4 weeks (4.7 +/- 1.2 micrograms/mg, P less
 than .001); in the ob/ob mice it was less than 20% that of controls (2.1
 +/- 0.8 vs 12.2 +/- 3.6 micrograms/mg protein). In kidneys, the EGF content
 was not altered in either ob/ob (524 +/- 50 vs 571 +/- 33 pg/mg protein)
 or STZ mice (652 +/- 183 vs 665 +/- 80 pg/mg). The preproEGF mRNA level in
 STZ-treated mice was reduced after 4 weeks in submandibular glands but not
 in kidneys. The results show that diabetes affects EGF production,
 utilization and/or excretion in mice and that kidneys are spared from
 suppression of EGF synthesis that is pronounced in the submandibular glands.
 PMID: 2402191, UI: 90384308
----

 endodermico, ma da quello mesodermico....
Considerazione molto interessante, e alla quale è data una risposta nelle
referenze [6] [7] [8].  Noto anche che gli elevati valori di EGF nei fluidi
giallo, bianco e azzurro (urina, latte e sperma) riportati nelle ref. (1)
("80 ng/ml in urine, 65 ng/ml in milk, 50 ng/ml in seminal plasma") e (2)
del mio post precedente, trovano una spiegazione teorica in quanto esposto
nella [7] dove è scritto che gli organi classicamente più responsivi all'EGF
sono la pelle e l'apparato digerente, più quelli che vanno incontro alla
morfogenesi a diramazione durante lo sviluppo: oltre a polmone e pancreas,
il rene (da cui l'EGF nell'urina), la ghiandola mammaria (EGF nel latte)
e la prostata (EGF nello sperma).
Ma a che cosa serve, in definitiva, la produzione di EGF da parte del rene?
A quel che pare, serve ad evitare l'apoptosi dello stesso, che si verifica
ad esempio nell'idronefrosi e nei casi di ischemia seguita da riperfusione
(come avviene anche nel corso di grandi interventi di chirurgia vascolare)
[9] [10] [11] [12] [13] [14].  E sono state ottenute prove sperimentali
che la somministrazione di EGF riduca tali danni [15] [16].
Ora, acquisite queste evidenze sperimentali sul contenuto di EGF nei fluidi
corporei e le spiegazioni accreditate sul suo significato, vediamone infine
un paio di possibili applicazioni terapeutiche.
Il contenuto di EGF nel latte (per cui suppongo che contribuisca ad evitare
l'insorgenza dell'ulcera peptica nel neonato) può rendere conto dell'azione
positiva del latte nell'ulcera gastrica.  Ma esistono prove sperimentali che
la somministrazione di EGF incida favorevolmente sull'ulcera?  Sì: vedasi
la ref. [17].  Tuttavia notiamo che il latte vaccino dovrebbe contenere
(per caratteristiche evolutive di sviluppo e di alimentazione dei piccoli)
meno EGF di quello umano, e inoltre la pastorizzazione ne diminuisce
certamente l'attività.  Quindi l'azione anti-ulcera del latte di vacca
dovrebbe essere inferiore a quella del latte di donna.  Quest'ultimo però
non è ovviamente disponibile che per i neonati.  A questo punto uno potrebbe
forse farsi venire in mente di bere a tale scopo l'urina... ebbene, ciò
è estremamente sconsigliabile, perché l'urina contiene anche prodotti di
rifiuto del metabolismo che andrebbero a intossicare il fegato.  Non a caso
il famigerato Vanoli ha un colorito giallognolo caratteristico dell'ittero
da epatite tossica: quindi non seguite il suo folle esempio.  Sarà bene
invece aspettare che le ricerche portino a qualche specialità farmaceutica
a base di EGF.
Ultima considerazione.  Noto che nel diabete la produzione di EGF da parte
delle ghiandole sottomandibolari è ridotta, mentre la sua escrezione
con l'urina no [18] [19], almeno fino a quando non s'instaura una franca
nefropatia diabetica.  Da ciò io pervengo all'ipotesi interessante che un
diabetico con parodontopatia (tengo a precisare che la cosa non riguarda me)
potrebbe forse trarre un giovamento dall'effettuazione di collutori orali
con la propria urina (senza berla!), alla stregua degli antichi Celtiberi.
Tuttavia anche in questo caso occorrerebbe essere certi che non siano
presenti infezioni delle vie urinarie (di cui un aspetto torbido dell'urina
è un possibile indizio).  Concludo ricordando che questa considerazione è
solo un'ipotesi speculativa e non rappresenta in alcun modo un'esortazione
a metterla in atto da parte di chicchessia (evento per il quale declino
sin d'ora qualsiasi responsabilità a riguardo delle possibili conseguenze).
Saluti.
  -= Ginzo =-

 che la somministrazione di EGF riduca tali danni [15] [16].
Bell'articolo Ginzo, l'ho trovato davvero interessante.
Aggiungo solo che il rene e` un organo di per se sottoposto a stress e
che ci sono vari e complessi meccanismi molecolari di difesa attivi
anche in condizioni fisiologiche, che ci sia quindi un'alta produzione
di EGF e perfettamente logico in quel contesto (tra l'altro  su questo
argomento ho lavorato direttamenete e anche se non e` stato il mio
progetto principale sono coautore di una recente publicazione su
american journal of physiology nella quale mostriamo come un splicing
alternativo della chinasi stress attivata p38 e` espressa solo nei
tubuli distali del rene, ma qui sto divagando).
-- 
Ciao, Carlo Fusco

 e` espressa solo nei tubuli distali del rene, ma qui sto divagando).
Non stai affatto divagando, visto che l'argomento è sempre in tema.
Chiaramente il fatto che Omi e Mxi2 siano regolate dall'ischemia renale
induce a pensare che possano avere interazioni con l'EGF.  Perciò riporto
anche l'abstract di questo tuo ultimo lavoro [2] e mi complimento con te.
Saluti.
  -= Ginzo =-
  [1] J Biol Chem 2000 Jan 28;275(4):2581-8
 Characterization of a novel human serine protease that has extensive
 homology to bacterial heat shock endoprotease HtrA and is regulated
 by kidney ischemia.
 Faccio L, Fusco C, Chen A, Martinotti S, Bonventre JV, Zervos AS
 Cutaneous Biology Research Center, Massachusetts General Hospital,
 Charlestown, Massachusetts 02129, USA.
  We report the isolation and characterization of a cDNA encoding the novel
 mammalian serine protease Omi. Omi protein consists of 458 amino acids
 and has homology to bacterial HtrA endoprotease, which acts as a chaperone
 at low temperatures and as a proteolytic enzyme that removes denatured or
 damaged substrates at elevated temperatures. The carboxyl terminus of Omi
 has extensive homology to a mammalian protein called L56 (human HtrA),
 but unlike L56, which is secreted, Omi is localized in the endoplasmic
 reticulum. Omi has several novel putative protein-protein interaction
 motifs, as well as a PDZ domain and a Src homology 3-binding domain.
 Omi mRNA is expressed ubiquitously, and the gene is localized on human
 chromosome 2p12. Omi interacts with Mxi2, an alternatively spliced
 form of the p38 stress-activated kinase. Omi protein, when made in
 a heterologous system, shows proteolytic activity against a nonspecific
 substrate beta-casein. The proteolytic activity of Omi is markedly
 up-regulated in the mouse kidney following ischemia/reperfusion.
 PMID: 10644717, UI: 20112822
  [2] Am J Physiol Cell Physiol 2000 Apr;278(4):C781-90
 Mxi2, a splice variant of p38 stress-activated kinase, is a distal nephron
 protein regulated with kidney ischemia.
 Faccio L, Chen A, Fusco C, Martinotti S, Bonventre JV, Zervos AS
 Cutaneous Biology Research Center, Massachusetts General Hospital/
 Harvard Medical School, Charlestown, Massachusetts 02129, USA.
  Mxi2 is one of three known alternative spliced forms of the stress-
 activated mitogen-activated protein kinase p38 (CSBP). Mxi2 was originally
 identified as a Max-interacting protein and is the smallest member of the
 family of stress-activated kinases isolated to date. Mxi2 lacks most of the
 XI domain found in p38 and instead has a distinct COOH-terminal sequence
 of 17 amino acids. Here we present the genomic structure of the Mxi2/p38
 locus on human chromosome 6q21.2/21.3 and establish the origin of the
 three spliced forms of p38. Using Mxi2-specific antibodies in mouse
 organs, we found the Mxi2 protein to be present exclusively in the kidney.
 Mxi2 is present predominantly in the distal tubule of the nephron and
 the level of the protein decreased during kidney ischemia-reperfusion.
 Stress signals or other known activators of the p38 pathway including MAP
 kinase-kinase 3 and MAP kinase-kinase 6 did not induce the kinase activity
 of Mxi2 using ATF-2 as a substrate. With the use of hybrid proteins encoding
 different portions of Mxi2 and p38 polypeptides, the different properties
 of Mxi2 can be assigned to its unique COOH terminus.
 PMID: 10751326, UI: 20217347
----

 E noi l'urina dovremmo BERLA??? :-P
Sai benissimo che non io ho mai sostenuto questo!  Tuttavia mi pare ormai
innegabile che i fattori di crescita contenuti in quei liquidi svolgano
un ruolo fisiologico importante, che in caso di necessità e allorché il
rapporto tra benefici e danni risulti favorevole, potrebbe essere convertito
in un ruolo terapeutico.  Ovviamente occorreranno studi scientifici seri
(non le stupidaggini di Vanoli) per poter confermare ciò anche per l'urina
(per il latte materno non credo che ci siano dubbi).
Saluti.
  -= Ginzo =-
REFERENZE:
  [1] Dig Dis Sci 1995 Nov;40(11):2295-9
 Gastroprotection by dairy foods against stress-induced ulcerogenesis
 in rats.
 Dial EJ, Romero JJ, Lichtenberger LM
 Department of Physiology and Cell Biology, University of Texas-Houston
 Medical School 77225, USA.
  We investigated the ability of three dairy foods to prevent stress-induced
 gastric lesions and bleeding in rats. Skim milk, whole milk, and cream
 were all significantly gastroprotective with the greatest protection seen
 with the highest fat dairy food. Pretreatment of rats with cream for up
 to 2 hr prior to stress maintained a portion of the protective effect.
 Lipid extracts of cream, but not skim milk or whole milk, were gastro-
 protective. Surface hydrophobicity of the gastric mucosa was reduced
 by stress, but was maintained at prestress levels by treatment with milk,
 cream, or their lipid extracts, although this effect was not sufficient
 for protection in stressed rats. Alterations in gastric pH or titratable
 acid could not explain the protective effects of dairy foods or their
 lipid extracts. Milk was more gastroprotective in stressed rats than
 another food of equal caloric value. We conclude that both the lipid
 and nonlipid fractions of dairy foods possess gastroprotective activity
 against stress-induced ulcerogenesis in rats, a property that may be
 of therapeutic value for man.
 PMID: 7587804, UI: 96083445
  [2] Nutrition 1998 Oct;14(10):771-4
 Growth factors and the gastrointestinal tract.
 Murphy MS
 Institute of Child Health, Birmingham, UK. 
m.s.m...@bham.ac.uk
  This paper reviews areas of interest in gut mucosal growth factor
 physiology. Several epidermal growth factor (EGF)-like peptides (EGF,
 transforming growth factor [TGF]-alpha, heparin-binding EGF-like peptide,
 amphiregulin, and betacellulin) have been identified in the gut, EGF is
 produced by the salivary glands and is present in milk. It may act on the
 mucosa from the lumen as a surveillance peptide promoting mucosal repair.
 A stem-cell-derived "ulcer-associated cell lineage" develops adjacent to
 ulcers and produces EGF, which may play a role in ulcer healing. TGF-alpha
 is expressed by villus enterocytes and may have an important role in mucosal
 healing. The Trefoil peptides (pS2, spasmolytic polypeptide, intestinal
 trefoil factor) are protease resistant molecules secreted by mucin cells
 throughout the gut, with a role in mucosal healing. The TGF-beta family
 inhibit cell proliferation, and promote cell differentiation. TGF-beta
 has a gradient of expression along the crypt villus axis, with maximum
 production at the villus tip. It is suspected that it may prevent cell
 proliferation and support differentiation of villus enterocytes. Hepatocyte
 growth factor is a multifunctional growth factor expressed in many tissues,
 including the gastrointestinal tract. It has a role in organogenesis.
 Intestinal adaptation is highly dependent on enteral nutrition, and it is
 likely that growth factors are involved in adaptation. Little is known,
 however, about interactions between nutrients and growth factors. Milk
 contains a range of potentially important growth factors. Their biological
 significance is uncertain, and this is an area of active research.
 PMID: 9785359, UI: 99001538
  [3] Med Hypotheses 2000 Mar;54(3):432-433
 How calcium from calcium carbonate and milk benefit peptic ulcer patients.
 Wang X
 Cornell University Medical College, New York, USA
  Calcium from calcium containing antacids and milk enhance the integrity
 of gastrointestinal mucosa and mucus, as it is the natural linker agent
 of these structures, which strengthens their defense function.
 PMID: 10783482
  [4] Gastroenterology 1978 Oct;75(4):649-54
 Predisposition to gastric erosions in the rat: behavioral and nutritional
 effects of early maternal separation.
 Ackerman SH, Hofer MA, Weiner H
  After early maternal deprivation (on postnatal day 15), the incidence of
 restraint-induced gastric erosions on day 30 increases to approximately
 5 times that of rats separated at the customary (day 21) weaning age.
 These data suggest that factors in the mother-infant relationship during
 postnatal development in young rats can influence later susceptibility or
 resistance to gastric erosions. We present a series of experiments to test
 whether loss of behavioral interaction with the mother or loss of maternal
 milk results in this increase in gastric erosion susceptibility. The results
 show that the absence of maternal milk, rather than behavioral deprivation,
 is primarily responsible for the increase in susceptibility after early
 maternal separation. However, behavioral interaction with the mother can
 additionally modify this susceptibility.
 PMID: 710833, UI: 79046196
  [5] J Pediatr Surg 1979 Dec;14(6):803-8
 The identification and clinical implications of human breast milk mitogen.
 Tapper D, Klagsbrun M, Neumann J
  There are constituents of human breast milk that make it superior to cow's
 milk for the nutrition, health and development of human infants. We have
 discovered a new activity in breast milk. We have found in human breast milk
 a mitogen that stimulates DNA synthesis and induces division in cells grown
 in culture. This mitogenic activity is concentration dependent, and also
 depends on time since lactation. No similar mitogenic activity is found in
 commercially available formulas or cows milk 1 wk after birthing. The human
 milk mitogen might be involved in the growth and development of cells in
 the neonate. It may be important in preventing necrotizing entercolitis and
 peptic ulceration of the newborn. It might also be used in the treatment
 of infants following massive small bowel resection.
 PMID: 575904, UI: 81009023
----

(per il latte materno non credo che ci siano dubbi).
Io invece (vedi prima) qualche dubbio ce l'ho  :-)) Infatti la
deprivazione precoce di latte materno determina (nel ratto) ulcera da
stress non solo per motivi nutrizionali ma anche "comportamentali" (e
tu sai quanto sia importante quest'ultimo aspetto nella genesi delle
patologie gastrointestinali). Non solo: la precoce deprivazione del
latte materno costringe all'uso di pratiche di Weaning prima che la
mucosa gastrica ed intestinale siano teoricamente "mature" per
sopportarle. L'EGF probabilmente c'entra....ma non è il fattore
determinante. Infatti in [4] troviamo testualmente: "These data
suggest that factors in the mother-infant relationship during
postnatal development in young rats can influence later
susceptibility or resistance to gastric erosions."
Come suggerito nell'ultima referenza che porti, infine, sono d'accordo
sul fatto che (per tanti motivi e non solo l'EGF) il latte materno sia
quanto di meglio per il neonato così come il latte di vacca sia il
meglio per il vitello e così via. Nell'articolo ci sono, tuttavia, un
sacco (troppi, per i miei gusti) di "might". Forse sarebbe stato più
interessante portare dati e non supposizioni. Nun vale: così sò bbono
pur'io  :-))))
Ciao
Docpocket (Stefano)

...
...a proposito di latte vaccino, latte di donna, EGF e quant'altro (ma
direi più propriamente a complemento di quanto da me scritto nel post
precedente).
IL LATTE VACCINO E' CONTROINDICATO NEI LATTANTI? (perchè contiene meno
EGF del materno) ?
La risposta è NO (per ciò che riguarda l'EGF, ovviamente)  :-))))
In [1], infatti, l'esperienza dei ricercatori avvalora l'ipotesi che
il latte vaccino contenga una sostanza (non ancora isolata) che
agirebbe da fattore protettivo nei confronti della proteolisi dell'EGF
di derivazione gastrica ed intestinale. Questo dimostrerebbe che il
latte vaccino, lungi dall'essere controindicato nell'alimentazione
infantile, potrebbe addirittura essere auspicabile.
L'EGF NEL LATTE E' UN COMPONENTE IRRINUNCIABILE PER LA PROTEZIONE
DALL'ULCERA GASTRICA DEL NEONATO?
La risposta è: PROBABILMENTE NO
A conferma di quanto ipotizzavo nel post precedente (e cioè che l'EGF
presente nel latte venga prodotto solo per favorire lo sviluppo e la
riparazione tissutale duttale, la differenziazione della mammella e la
produzione di latte) ho trovato un lavoro [2] (veramente più di
uno...ma tutti con lo stesso contenuto) nel quale viene ad essere
sottolineato questo ruolo del peptide con dimostrazioni sperimentali.
In questo senso ritengo che potremmo dar valore alla mia ipotesi che
l'EGF nel latte non sia altro che l'eccedenza di questa proteina di
produzione acinare e duttale e che sullo stomaco del neonato e del
lattante abbia un ruolo secondario in quanto a protezione dall'ulcera
(lasciando il principale ai growth factors di produzione mucosa).
Ritengo invece molto più verosimile l'ipotesi (ovviamente non mia) che
svolga funzioni di stimolo alla maturazione delle cellule epiteliali
del tratto gastrointestinale (ed è tutto un altro discorso), tanto è
vero che in piglets di 3 giorni (dopo sua somministrazione previa
marcatura) lo si ritrova intero sia nel lume che nella parete di
stomaco, piccolo intestino e colon, fino a 45 minuti di distanza.
L'EGF di derivazione esogena, in questo senso, avrebbe un significato
differente da quello dell'EGF endogeno.
IL LATTE "FA BENE" NELL'ULCERA?
La risposta è NO! (ci metto anche il punto esclamativo)  :-)))
Per avvalorare il fatto che latte (come tale) e ulcera non vanno
d'accordo, riporto quanto potrai leggere in [3]. Si segnala, nello
studio, che mentre i derivati "fermentati" del latte svolgono
un'azione preventiva nei confronti dell'ulcera peptica, il latte tout
court può esserne addirittura il movente.
Sono solo precisazioni di quanto affermavo nel post precedente, Ginzo.
Non ho intenzione di contraddirti perchè quanto dici ha un fondo di
verità (e conferme sperimentali sul ruolo dell'EGF ce ne sono a iosa).
Volevo semplicemente segnalarti alcune piccole e "minori" imprecisioni
nelle tue affermazioni, un lavoro che può essere utile a chi legge per
sfrondare le ipotesi dai dati certi ed il vero dall'impreciso.  :-))
Mi scuso per la prolissità ed auguro, a chi sia interessato, una buona
lettura  :-))))
-----------------------------------------------
[1] Bovine milk inhibits proteolytic degradation of epidermal growth
factor in human gastric and duodenal lumen.
Peptides 1998;19(3):495-504   (ISSN: 0196-9781)
Rao RK; Baker RD; Baker SS
Department of Pediatrics, Medical University of South Carolina,
Charleston 29407, USA.
Degradation of epidermal growth factor (EGF) in human gastric and
duodenal lumen was analyzed by incubating 125I-labeled or unlabeled
human recombinant EGF with human gastric or duodenal luminal fluids in
vitro. Degradation of EGF was assessed by measuring the generation of
acid soluble radioactivity or by reversed-phase high-performance
liquid chromatography (HPLC). Incubation with gastric luminal fluids
resulted in a time- and dose-dependent degradation of labeled and
unlabeled EGF at pH 2.5 but not at pH 7.5. Duodenal luminal fluids, on
the other hand, degraded EGF at pH 7.5 but not at pH 2.5. The rate of
degradation of unlabeled EGF in gastric luminal fluids was nearly
12-fold higher than the rate of degradation of labeled EGF, whereas
only a slight difference in rates of degradation of labeled and
unlabeled EGF was observed in duodenal luminal fluids.
High-performance liquid chromatography analysis detected three major
degradation products that eluted with retention time of 17.5 min, 20.0
min, and 22.5 min that was associated with a reduction of intact EGF
(retention time 23.5 min). Defatted and decaseinated supernatant of
bovine milk effectively inhibited the degradation of EGF in both
gastric and duodenal luminal fluids. Dietary derived protease
inhibitors, such as soya bean trypsin inhibitor, lima bean trypsin
inhibitor, egg white protease inhibitor, and Bowman-Birk protease
inhibitor prevented EGF degradation in duodenal luminal fluids but
failed to inhibit EGF degradation in gastric luminal fluids. These
results suggest that bovine milk may contain specific inhibitors that
protect EGF from proteolytic degradation in human gastric lumen.
----------------------------
[2] EGF and TGF alpha modulate structural and functional
differentiation of the mammary gland from pregnant mice in vitro:
possible role of the arachidonic acid pathway.
J Cell Biochem 1995 Mar;57(3):495-508   (ISSN: 0730-2312)
Spitzer E; Zschiesche W; Binas B; Grosse R; Erdmann B [Find other
articles with these Authors]
Max-Delbruck-Center for Molecular Medicine, Berlin-Buch, Germany.
Epidermal growth factor (EGF) has been suggested to be involved in
mammary gland development by mitogenic stimulation of the ductal and
alveolar epithelium in virgin mice. The present studies demonstrate
that also in late-pregnant mice EGF leads to proliferation of the
ductal, ductular, and alveolar epithelium. The mitogenic effect is
associated with structural and functional dedifferentiation of
alveolar cells as revealed by analysis of morphology, expression of
cytosolic and secretory proteins, and fatty acid synthesis. Using a
combination of metabolic inhibitors, the dedifferentiating effect of
EGF could be blocked while the mitogenic action was not influenced.
This finding demonstrates that the signal transduction pathway leading
to dedifferentiation and mitosis can be separated, and that the
dedifferentiating effect of EGF is independent of its mitogenic
properties, but is probably mediated by activation of the arachidonic
acid-dependent pathways (cyclo- and lipoxygenase pathways). Release of
arachidonic acid from the endogenous phospholipid pool was found to be
an early response of the explants to EGF. Accordingly, arachidonic
acid itself proved to be capable of inducing epithelial
dedifferentiation but failed to stimulate proliferation. TGF alpha
showed qualitatively similar effects as EGF but was generally a
stronger agonist. It is suggested that EGF and TGF alpha also play a
role in mammary gland physiology during pregnancy by final developing
and maintenance of the lobulo-alveolar structure in the mammary gland
and prevention of premature onset of lactation, and that this is
mediated through the PLA2-arachidonic acid signalling cascade.
-------------------------------------
[3] Fermented milk products are associated to ulcer disease. Results
from a cross-sectional population study.
Eur J Clin Nutr 1998 Sep;52(9):668-74   (ISSN: 0954-3007)
Elmstahl S; Svensson U; Berglund G [Find other articles with these
Authors]
Department of Community Medicine, Lund University, Malmo University
Hospital, Sweden.
BACKGROUND: Prevalence of peptic ulcer disease has been associated to
diet. Some dietary factors seem to have bactericidal effect which may
modify the risk of peptic ulcer disease. The objective was to analyze
associations between dietary habits and peptic ulcers. DESIGN: A cross
sectional population study. SUBJECTS: One thousand, one hundred and
thirty-five subjects out of 11700 randomly invited men and women, aged
46-67 y, participating in a diet and disease study during 1991-1993.
The study population comprised of 764 cases with reported peptic
ulcer, 142 with dyspeptic symptoms and 229 randomly selected controls.
METHODS: X-ray examinations and endoscopies were reviewed and 332 out
of 764 peptic ulcer cases were verified. Mean daily intake of foods
and nutrients were assessed with a combined 7d menu book and a
quantitative food frequency questionnaire, including dietary
supplements. RESULTS: Subjects with verified ulcer had lower intake of
fermented milk products and vegetables and higher intake of milk, meat
and bread than controls. Intake of total fat, saturated and
monounsaturated fatty acids and linolenic acid were higher in the
ulcer group. Higher intake of fermented milk products, by quintiles
showed a decreased ulcer risk; odds ratio 0.82 (0.71-40.95), adjusted
for covariates below. Higher intake of milk, by quintiles, was
associated with an increased risk of ulcer; odds ratio 1.17
(1.03-1.32). Smoking, foreign ethnicity and being unmarried or
divorced were covariates associated to ulcer. CONCLUSION: This study
indicates the multifactorial etiology of peptic ulcer including
dietary factors. High intake of fermented milk products was associated
with decreased risk for ulcer, whereas increased risk was noted for
high milk intake.
-------------------------------------
Hallo everybody  :-)))
Docpocket

Ciao Ginzo  :-))))
Qualche nota sull'EGF e sui suoi recettori, a proposito dell'eventuale
ruolo "terapeutico" dell'EGF nella "riparazione" degli epiteli.
Tra le numerose conseguenze dell'interazione tra EGF ed il suo
recettore (EGF-R), se ne rileva una che è particolarmente
interessante. All'aumento della concentrazione dell'EGF, e alla
saturazione progressiva dei suoi recettori cellulari espressi a
livello superficiale, corrisponde un feedback negativo nell'
esposizione dei medesimi. Questi, infatti, all'aumentare della
concentrazione in EGF, tendono a "migrare" a livello intracellulare
(sottraendosi quindi all'interazione col peptide) dove vengono
sottoposti a degradazione da parte dei lisosomi. Ciò induce una
attenuazione di tutte le altre risposte mediate dall'interazione tra
EGF e EGF-R.
Un interessante studio [1] condotto a tal riguardo dimostra come l'EGF
eterologo (per la cronaca: "somministrato" e quindi non prodotto dalle
cellule stesse) provochi tale meccanismo di feedback, rendendo meno
efficace (in via retrograda) l'azione dell'EGF di produzione endogena.
Comunque che l'EGF sia, per l'organismo, benefico o "malefico", viene
deciso NON dalla concentrazione dell'EGF stesso ma dalla presenza e
dalla quantità di recettori espressi a livello cellulare e tissutale.
Alcuni esempi?
Nel 48% dei cancri della mammella l'EGF-R è in eccesso e l'azione "in
esubero" dell'EGF determina difetti nella mitogenesi. Sia in vivo che
in vitro è stato rilevato infatti [2] un effetto di rallentamento
nella differenziazione cellulare (rispetto al suo potenziale) ed una
tendenza alla trasformazione cancerosa delle cellule stesse.
Un significativo studio [3] rileva inoltre la presenza di EGF-R nelle
cellule di Schwann isolate dal Neurofibroma tipo 1--..ed in queste
cellule (di norma) l'EGF-R non è espresso affatto.
Nel cancro del colon è stata ottenuta [4] (usando FANS) un'
attenuazione della proliferazione neoplastica mediante blocco della
pompa del Calcio che, in via retrograda, inibisce l'azione dell'EGF.
Nei pazienti con cheratocongiuntivite secca, infine, è stata rilevata
[5], a livello epiteliale, una esuberanza degli EGF-R ed è stato
ipotizzato quindi un suo ruolo centrale nell'iperplasia delle cellule
congiuntivali e nella produzione di cheratina.
Ci sarebbero decine di altri possibili esempi ma mi fermo perché ,
alla luce di quanto sopra, mi vengono già in mente possibili e
plausibili risposte ai quesiti sorti nel corso del thread.
1) Bere urina per recuperare l'EGF? Non mi sembra il caso per tante
ragioni. Che facciamo? Prima lediamo la mucosa e scassiamo il fegato
(coi tossici urinari) e poi speriamo nell'azione rigeneratrice dell'
EGF? E questo, ovviamente, nell'ipotesi migliore (cioè che l'EGF
esogeno sia effettivamente apportatore di quest'effetto)
2) Isolare l'EGF dai fluidi corporei a scopo terapeutico? Anche qui
sono perplesso, dato che l'eccesso di EGF esogeno porta ad una
diminuzione dei suoi recettori tissutali, per feedback negativo,
vanificandone l'azione.
3) L'EGF del latte protegge il neonato dall'ulcera? Stesso discorso di
(2).
Non so che dire: ho dei fortissimi dubbi, Ginzo. Lo studio è appena
all'inizio ma ho la sensazione (leggendo i più recenti articoli di cui
più sotto riporto gli estremi) che l'EGF è meglio lasciarlo dov'è,
studiarlo bene e non giocarci  troppo. Mi da l'idea di una di quelle
cose che, se maneggiate con troppa disinvoltura, ti scoppiano in mano.
Con stima
Docpocket
---------------------------------------------------------------
Referenze (Marzo/Giugno 2000)
[1] Immunoelectron microscope analysis of EGF-R in isolated Mytilus
Galloprovincialis digestive gland cells: evidence for ligand-induced
changes in EGF-R intracellular distribution
Canesi L; Malatesta M et al.
Ist. Scienze Fisiol.  Urbino  Italy
J Exp Zool   2000 Jun;286(7):690-698  (ISSN: 0022-104X)
[2] Mammary gland specific EGF-R transgene expression induces
neoplasia and inhibits differentiation
Brandt R, et al.
Schering Research Laboratories, Berlin, Germany
Oncogene 2000 Apr 20;19(17):2129-2137  (ISSN: 0950-9232)
[3] EGF-R expression in neurofibromatosis Type 1-related tumors and
NF1 animal models
De Clue et al.
National Cancer Institute, Bethesda, Maryland USA
J Clin Invest 2000 May;105(9):1233-1241  (ISSN: 0021-9738)
[4] NSAIDs attenuate proliferation of colonic carcinoma cells by
blocking EGF-induced Ca++ mobilization
Kokoska ER et al.
Theodore Cooper Surg. Res. Inst., St.Louis University, Missouri
J Gastroenterol Surg 2000 Mar;4(2):150-161  (ISSN 1091-255X)
[5] Increased expression of the type 1 growth factor receptor family
in the conjunctival epithelium of patients with keratoconjunctivitis
sicca
Liu Z, Carvajal M et al.
Ocular Surface and Tear Center, Bascom Palmer Eye Institute, Miami,
Florida, USA
Am J Ophtalmol 2000 Apr;129(4):472-480  (ISSN 0002-9394)
-------  Per ovvi motivi non posto gli abstracts. Chi fosse
interessato può chiedermeli e li spedirò
olentieri  -----------------------------------------------------------
-----------------------------------------

   -= Ginzo =-
Ciao 
Mariano

 cose che, se maneggiate con troppa disinvoltura, ti scoppiano in mano.
Purtroppo la cosa è scoppiata in mano a te, visto che nel latte ce n'è quasi
quanto nell'urina... e in più nel latte ci sono anche IGF e insulina bovina.
Come ti ho già accennato, il latte vaccino è stato sospettato (e ci sono
sempre più indizi al riguardo) di essere diabetogeno.  Se non fosse per
le sostanze di scarto contenute nell'urina, forse ci sarebbe da preoccuparsi
maggiormente di quelli che bevono latte anziché di quelli che bevono urina!
Saluti.
  -= Ginzo =-
REF.:
  [-1c] Curr Eye Res 1999 Sep;19(3):201-11
 Altered cytokine balance in the tear fluid and conjunctiva of patients
 with Sjogren's syndrome keratoconjunctivitis sicca.
 Pflugfelder SC, Jones D, Ji Z, Afonso A, Monroy D
 Ocular Surface and Tear Center Bascom Palmer Eye Institute University of
 Miami School of Medicine Department of Ophthalmology Miami, FL 33136, USA.
 
spflgu...@bpei.med.miami.edu
  PURPOSE. To compare epidermal growth factor (EGF) concentration in tear
 fluid and levels of inflammatory cytokines in the conjunctival epithelium
 of patients with Sjogren's syndrome keratoconjunctivitis sicca with those
 of normal controls. [...] RESULTS. Decreased tear fluid EGF concentration
 was noted in Sjogren's syndrome patients (mean 0.68 +/- 0.59 ng/ml) compared
 to controls (mean 1.66 +/- 0.45 ng/ml, P = 0.004). Significantly increased
 levels of IL-1alpha, IL-6, IL-8, TNF-alpha and TGF-beta1 RNA transcripts
 were found in the conjunctival epithelium of Sjogren's syndrome patients
 compared to controls (P < 0.05), while the level of G3PDH was similar in
 both groups. The concentration of IL-6 protein was significantly higher
 in Sjogren's syndrome conjunctiva samples (P = 0.012). [...] CONCLUSIONS.
 The balance of cytokines in the tear fluid and conjunctival epithelium is
 altered in Sjogren's syndrome. The severity of keratoconjunctivitis sicca
 in this condition increases as tear fluid EGF concentration decreases and
 levels of inflammatory cytokines in the conjunctival epithelium increase.
 These findings provide new insight into the pathogenesis of
 keratoconjunctivitis and provide potential targets for therapy.
 PMID: 10487957, UI: 99418961
----

 Carcinoma METASTATICO....., non primitivo  :-)))
Appunto: non è stata l'urina dell'urinoma a provocarlo.  Il mio discorso
era che non è facile distinguere la causa dall'effetto: se una lesione
precancerosa fa sì che la mucosa vescicale si fissuri e l'urina s'infiltri,
a rigore non puoi provare da questo fatto che sia stata l'urina a indurre
quella lesione precancerosa (magari è stato un calcolo o uno schistosoma).
Saluti.
  -= Ginzo =-
REFERENZE:  ( - : testo condensato;  a : referenza di questo specifico post)
  [-1a] Life Sci 1996;59(3):197-208
 Stability of epidermal growth factor in the gastrointestinal lumen
 of suckling and weaned pigs.
 Shen WH, Xu RJ
  The stability of epidermal growth factor (EGF) in the gastrointestinal
 lumen of 3-day-old suckling and 45-day-old weaned pigs was examined [...]
 The results showed that hEGF was quite stable in the gastric fluids in
 both suckling and weaned pigs with less than 20% degradation after 20 min
 incubation. [...] These results indicate that milk-borne EGF is stable
 in the gastric and proximal intestinal lumen in suckling pigs, and may
 play a role in regulating postnatal development in the suckling young.
 PMID: 8699930, UI: 96276470
  [-2a] Peptides 1998;19(3):495-504
 Bovine milk inhibits proteolytic degradation of epidermal growth factor
 in human gastric and duodenal lumen.
 Rao RK, Baker RD, Baker SS
  Degradation of epidermal growth factor (EGF) in human gastric and duodenal
 lumen was analyzed [...] Incubation with gastric luminal fluids resulted
 in a time- and dose-dependent degradation of labeled and unlabeled EGF
 at pH 2.5 but not at pH 7.5. [...] Defatted and decaseinated supernatant
 of bovine milk effectively inhibited the degradation of EGF in both gastric
 and duodenal luminal fluids. [...] These results suggest that bovine milk
 may contain specific inhibitors that protect EGF from proteolytic
 degradation in human gastric lumen.
 PMID: 9533637, UI: 98192321
  [-3a] Life Sci 1998;63(10):809-20
 Stability and distribution of orally administered epidermal growth factor
 in neonatal pigs.
 Shen WH, Xu RJ
  Stability and distribution of orally administered epidermal growth factor
 (EGF) were examined in newborn and 5-day-old pigs. [...] Based on liquid
 chromatography and trichloroacetic acid precipitation, a substantial amount
 of EGF recovered from the luminal contents (63-86%) and the gastrointestinal
 wall (42-81%) remained "intact". [...] These results indicate that most of
 orally ingested EGF remained in the gastrointestinal tract in neonatal pigs
 45 min after oral ingestion, and significant amount of the ingested EGF
 remained biologically active. It suggests that milk-borne EGF can survive
 in the gastrointestinal tract and may play a role in regulating gut
 development in neonatal animals.
 PMID: 9734700, UI: 98403769
  [4a] J Pediatr Gastroenterol Nutr 2000 Mar;30(3):299-304
 Stability of insulin-like growth factor I in the gastrointestinal lumen
 in neonatal pigs.
 Shen WH, Xu RJ
 Department of Zoology, University of Hong Kong, Hong Kong.
  BACKGROUND: Insulin-like growth factor (IGF)-I is present in the milk of
 various species. A prerequisite for any biological activity of milk-borne
 IGF-I in the suckling young is to survive the gastrointestinal luminal
 digestion. In the present study, the stability of IGF-I was examined in
 the gastrointestinal lumen in neonatal pigs. METHODS: Iodine-labeled IGF-I
 was incubated in the gastrointestinal luminal fluids of 3-day-old suckling
 and 45-day-old weaned pigs at 37 degrees C for 20 minutes. Degradation
 of the peptide was analyzed by trichloroacetic acid (TCA) precipitation,
 liquid chromatography, and receptor binding assay. RESULTS: IGF-I remained
 unchanged in the gastric fluids of suckling and weaned pigs when determined
 by TCA precipitation. IGF-I degraded 3%, 18%, and 37% in the luminal fluids
 of the proximal, mid and distal small intestine in suckling piglets compared
 with 53%, 62%, and 54% in weaned pigs. The results were supported by the
 chromatography and receptor binding analysis. Porcine colostrum had a
 capacity to protect IGF-I from gastrointestinal luminal digestion in weaned
 pigs. CONCLUSION: Milk-borne IGF-I is stable in the gastrointestinal lumen
 in suckling pigs and may play a role in regulating postnatal development
 in the suckling young.
 PMID: 10749415, UI: 20210986
----

 sfrondare le ipotesi dai dati certi ed il vero dall'impreciso.  :-))
E di ciň ti ringrazio sinceramente!  Certamente io ho commesso e commetterň
diversi errori, e correzioni come le tue non possono che farmi piacere.
Saluti.
  -= Ginzo =-
REFERENZE:
  [1b] J Anim Sci 1996 Oct;74(10):2509-22
 Intestinal effects of milkborne growth factors in neonates of agricultural
 importance.
 Odle J, Zijlstra RT, Donovan SM
 Department of Animal Science, North Carolina State University, Raleigh
 27695-7621, USA.
  Reduction of postnatal morbidity and mortality of mammalian neonates
 poses a significant challenge to agricultural and medical sciences.
 Because nutritional insufficiency and diarrhea represent major stressors,
 an understanding of factors mediating postnatal growth and development of
 the gastrointestinal tract is essential. This review explores the role that
 milkborne growth factors may play in stimulating functional development
 of the neonatal intestine, with emphasis on the porcine, bovine, and ovine
 species. Studies reporting milk concentrations and intestinal effects
 are reviewed, with emphasis on epidermal growth factor, insulin, and
 the insulin-like growth factors. Collectively, these studies suggest that
 milkborne growth factors may provide important regulatory signals to the
 neonatal intestine under both normal and pathophysiological states.
 PMID: 8904721, UI: 97060675
  [2b] Chung Hua Min Kuo Hsiao Erh Ko I Hsueh Hui Tsa Chih
       1997 Sep-Oct;38(5):332-7
 Growth factors in breast milk and their effect on gastrointestinal
 development.
 Oguchi S, Shinohara K, Yamashiro Y, Walker WA, Sanderson IR
 Department of Pediatrics, Juntendo University School of Medicine, Tokyo,
 Japan.
  Breast milk contains various biologically active factors including,
 hormones, peptide growth factors, and cytokines. Epidermal growth factor
 (EGF) and insulinlike growth factor-I (IGF-I) are two of the major
 milk-derived peptide growth factors. Colostrum contains higher levels
 of these growth factors than mature milk does, and, these factors are
 relatively resistant to proteolysis and stable in the G-I tract. There are
 specific receptors found in G-I mucosa. Luminal EGF and IGF-I stimulate
 growth and development of gastrointestinal tract. Intestinal epithelial
 Caco-2 cells are a good model for studying physiological roles of
 exogenous growth factors in the G-I development. Effect of EGF and IGF-I on
 proliferation, differentiation, and IGF-binding protein (IGFBP) production
 of intestinal Caco-2 cells were studied. Both EGF and IGF-I increased cell
 proliferation in dose dependent manner. The number of IGF-I receptors on
 Caco-2 cells increased after differentiation, in contrast to EGF binding
 which was reported to decrease. Caco-2 cells produced at least three IGFBPs,
 namely IGFBP-2, -3, and -4. The profile of these IGFBPs varied with
 differentiation. Secretion of IGFBP-2 and -3 increased with differentiation,
 but IGFBP-4 diminished. IGF-I stimulated mainly IGFBP-3 production, while
 EGF stimulated predominantly IGFBP-4. The effects of IGF-I and EGF on
 IGFBP secretion diminished with increasing cell differentiation. Thus, the
 interaction between intestinal epithelial cells and extrinsic growth factors
 are complex and the stage of differentiation is an important determinant
 of this phenomenon.
 PMID: 9401175, UI: 98064411
  [3b] Arch Pediatr 1998 Mar;5(3):298-306
 [-Bioactive factors in milk-]. [Article in French]
 Buts JP
 Unite de gastroenterologie pediatrique, cliniques universitaires Saint-Luc,
 universite catholique de Louvain, Bruxelles, Belgique.
  Human milk as well as the milk of several mammalian species contains,
 beside major nutrients and anti-infectious and immunocompetent substances,
 a group of biologically active substances called "milk-borne trophic factors"
 or "growth modulators". Milk-borne trophic can be classified into three
 groups: hormones and trophic peptides; nucleotides, nucleosides and derived
 substances; and polyamines, especially spermine and spermidine. Certain
 hormones and peptides such as growth hormone, insulin, insulin like-growth
 factor I (IGF-I), epidermal growth factor (EGF), prolactin and growth hormone
 releasing factor (GHRF) can influence directly newborn's metabolism after
 intestinal absorption and promote growth and differentiation of several
 organs and target tissues. They could exert a cytoprotective effect against
 toxins and toxic substances and reduce the potential risk of necrotizing
 enterocolitis. Nucleotides are present in human milk at high levels, and
 are precursors of nucleic acids, which implies that they can enhance growth
 and differentiation of several organs and tissues, especially the liver.
 Nucleotides from milk enhance lipid metabolism, lipoprotein synthesis and
 liver cell function and regeneration. In addition, they have a determinant
 action on the development of the gut associated lymphoid tissue (GALT).
 Lastly, polyamines, mainly spermine and spermidine, are polycationic
 substances virtually present in all cells, whose concentration in human milk
 is about ten times higher than in infant formulae. In addition, spermine and
 spermidine levels increase markedly during the first 3 days of lactation
 reaching, after 1 week, plateau levels which are respectively 12 and eight
 times higher than the levels measured at day 0. Although several experimental
 studies have shown that polyamines from the milk of lactating mammals
 determine important mitogenic, metabolic and immunological effects promoting
 growth and differentiation of the immature gastrointestinal tract of the
 offspring, their beneficial effects on growth and differentiation of the
 gastrointestinal tract in humans remain hypothetical. As a consequence,
 enrichment of milk formulae in one or in several trophic factors is an
 important but complex goal. Its practical realization is not realistic today
 because of a too great number of incertitudes. The most important is related
 to potential beneficial or adverse effects emerging at short or at long term
 and to the individual interactions of these substances which could be
 agonist and antagonist because they are naturally present in milk as a
 "complex cocktail" whose composition changes during the lactation period.
 PMID: 10328000, UI: 99259984
  [4b] J Pediatr Gastroenterol Nutr 2000 May;30(5):515-21
 Milk-borne insulin with trypsin inhibitor in milk induces pancreatic amylase
 development at the onset of weaning in rats.
 Kinouchi T, Koizumi K, Kuwata T, Yajima T
 Department of Nutritional Research, Nutrition Science Institute, Meiji Milk
 Products Co., Odawara, Japan.
  BACKGROUND: The physiologic significance of milk-borne hormones and growth
 factors for internal organs of suckling animals is poorly understood.
 In this study the significance of milk-borne insulin was evaluated, as well
 as its combination with trypsin inhibitor, and its role in the development
 of pancreatic digestive capacity at the time of weaning was investigated.
 METHODS: Experiments were performed using insulin-deficient milk formula
 (standard formula), insulin (20 ng/ml) formula, or insulin with trypsin
 inhibitor (1 U/ml) formula by a rat artificial-rearing technique.
 RESULTS: In 17-day-old rats administered standard formula, the plasma
 insulin level was as low as that in 14-day-old rats. When insulin-trypsin
 inhibitor formula was administered to rat pups, the plasma insulin level
 was significantly higher than those in rats given standard or insulin
 formula. In rats artificially reared on standard formula, the usual
 developmental increases in pancreatic amylase activity and plasma insulin
 concentration at the beginning of weaning did not occur. Insulin formula
 elevated the pups' plasma insulin concentration and amylase activity at
 the onset of weaning but not to the levels observed in mother-reared rats.
 In rats reared on insulin-trypsin inhibitor formula, the developmental
 increases in the plasma insulin concentration and amylase activity observed
 in mother-reared rats were induced. CONCLUSIONS: The present study
 demonstrates the necessity of milk-borne insulin for the development
 of pancreatic amylase during the weaning period.
 PMID: 10817281, UI: 20274982
----

 tutto questo con "l'urinoterapia".
Storicamente ci sono state applicazioni dell'urinoterapia (anche per gocce
oculari) di cui non si riusciva a capire il razionale.  Le recenti ricerche
sull'EGF contenuto nell'urina forniscono una base razionale alle eventuali
guarigioni conseguite con l'urinoterapia.  Con ciò non intendo dire che
tale pratica alternativa vada supportata o incoraggiata: ho inteso solo
dimostrare che a un'indagine scientifica attenta e perspicace è possibile
reperire dei fondamenti razionali anche per alcune pratiche alternative
che a prima vista possono sembrarci del tutto irrazionali.
Saluti.
  -= Ginzo =-
REFERENZE:
  [1d] Ned Tijdschr Geneeskd 1999 Dec 11;143(50):2511-4
 [Intestinal infections due to inhibition of gastric acid secretion
 in reflux disease]. [Article in Dutch]
 Otten MH
 Ziekenhuis Eemland, afd. Maag-, Darm- en Leverziekten, Amersfoort.
  Gastric acid stimulates the absorption of nutrients and is the most
 important non-immunological defence system against the constant bacterial
 invasion of our digestive tract. Patients with achlorhydria and resected
 stomachs have excessive growth of bacteria in the digestive tract and a much
 higher incidence of gastrointestinal infections. Modern treatment of reflux
 oesophagitis with acid secretion inhibitors creates a similar low acid state.
 Suppression of gastric acid secretion causes a dose dependent increased risk
 of a wide variety of intestinal infections especially for people over 65,
 immune compromised persons, sick patients with a reduced resistance and
 travellers to tropical areas. The potentially dangerous infections can be
 reduced by adequate counselling about the importance of gastric acid, the
 precaution of improved hygiene, on demand use of especially proton pump
 inhibitors and prescription of antacids and less potent acid inhibitors.
 PMID: 10627752, UI: 20093222
  [2d] Eur J Gastroenterol Hepatol 2000 Feb;12(2):145-7
 Safety of proton-pump inhibitors: the acid test.
 Moncur PH, Heatley RV
 St James's University Hospital, Leeds, UK. 
pe...@scotdoc.demon.co.uk
  It is well established that atrophic gastritis, pernicious anaemia and
 partial gastrectomy are associated with an increased risk of gastric
 carcinoma. These conditions all result in a low acid output state.
 Although the mechanism of gastric carcinogenesis is not known, the model
 proposed by Correa has provided the most attractive explanation to date.
 The suggestion is that prolonged hypochlorhydria predisposes to gastric
 carcinoma by an increase in the production of carcinogenic N-nitroso
 compounds. This hypothesis has led to concerns about the safety of
 long-term acid suppression in the management of a variety of acid-related
 gastrointestinal conditions.
 PMID: 10741926, UI: 20203970
  [3d] Curr Opin Ophthalmol 1998 Aug;9(4):50-3
 Advances in the diagnosis and management of keratoconjunctivitis sicca.
 Pflugfelder SC
 Department of Ophthalmology, Bascom Palmer Eye Institute, University of
 Miami School of Medicine, FL 33136, USA.
  Keratoconjunctivitis sicca is a common ocular surface disease that develops
 in patients with aqueous tear deficiency. Recent advances have been made in
 diagnosis, pathogenesis, and therapy of this condition. Advances in diagnosis
 include improved understanding of the specificity of the tests used for
 diagnosis, elucidation of the mechanism of the ocular surface rose bengal
 and fluorescein staining that occurs in this condition, and the expanded
 use of impression cytology. Advances in pathogenesis include the concept
 that keratoconjunctivitis sicca is a condition of abnormal growth and
 differentiation and immune activation of the ocular surface epithelium.
 These findings indicate that keratoconjunctivitis sicca may represent a
 chronic wound-healing response to a poorly lubricated and inflamed ocular
 surface. Advances in therapy include improved nonpreserved artificial tears
 and therapies targeted at decreasing ocular surface inflammation.
 PMID: 10387469, UI: 99260044
  [4d] Adv Exp Med Biol 1998;438:461-9
 Cytokines and tear function in ocular surface disease.
 Barton K, Nava A, Monroy DC, Pflugfelder SC
 Corneal and External Disease Service, Bascom Palmer Eye Institute,
 University of Miami School of Medicine, Florida, USA.
  In summary, tear EGF levels correlate most strongly with tear production
 in normals, and it is likely that some form of homeostatic mechanism exists
 to provide a constant supply to the ocular surface. Commercial ELISA kits
 appear to measure EGF in tears with good consistency and may be useful
 in the future to improve comparability of data from different studies.
 In addition, in ocular rosacea, which mimics keratoconjunctivitis sicca
 in a number of respects, there is a differential increase in the level
 of the inflammatory cytokine IL-1 alpha in the tear fluid. Much of this
 elevation appears to be the result of reduced tear turnover, which may form
 an important positive feedback mechanism encouraging tear stagnation and
 the perpetuation of ocular surface inflammation.
 PMID: 9634922, UI: 98298661
  [-5d] Curr Eye Res 1999 Sep;19(3):201-11
 Altered cytokine balance in the tear fluid and conjunctiva of patients
 with Sjogren's syndrome keratoconjunctivitis sicca.
 Pflugfelder SC, Jones D, Ji Z, Afonso A, Monroy D
 Ocular Surface and Tear Center Bascom Palmer Eye Institute University of
 Miami School of Medicine Department of Ophthalmology Miami, FL 33136, USA.
 
spflgu...@bpei.med.miami.edu
  PURPOSE. To compare epidermal growth factor (EGF) concentration in tear
 fluid and levels of inflammatory cytokines in the conjunctival epithelium
 of patients with Sjogren's syndrome keratoconjunctivitis sicca with those
 of normal controls. [...] RESULTS. Decreased tear fluid EGF concentration
 was noted in Sjogren's syndrome patients (mean 0.68 +/- 0.59 ng/ml) compared
 to controls (mean 1.66 +/- 0.45 ng/ml, P = 0.004). Significantly increased
 levels of IL-1alpha, IL-6, IL-8, TNF-alpha and TGF-beta1 RNA transcripts
 were found in the conjunctival epithelium of Sjogren's syndrome patients
 compared to controls (P < 0.05), while the level of G3PDH was similar in
 both groups. The concentration of IL-6 protein was significantly higher
 in Sjogren's syndrome conjunctiva samples (P = 0.012). [...] CONCLUSIONS.
 The balance of cytokines in the tear fluid and conjunctival epithelium is
 altered in Sjogren's syndrome. The severity of keratoconjunctivitis sicca
 in this condition increases as tear fluid EGF concentration decreases and
 levels of inflammatory cytokines in the conjunctival epithelium increase.
 These findings provide new insight into the pathogenesis of
 keratoconjunctivitis and provide potential targets for therapy.
 PMID: 10487957, UI: 99418961
  [-6d] Am J Ophthalmol 2000 Apr;129(4):472-80
 Increased expression of the type 1 growth factor receptor family in the
 conjunctival epithelium of patients with keratoconjunctivitis sicca.
 Liu Z, Carvajal M, Carothers Carraway CA, Carraway KL, Pflugfelder SC
 Ocular Surface and Tear Center, Bascom Palmer Eye Institute, Miami,
 Florida, USA.
  PURPOSE: To investigate the expression of type 1 growth factor receptors
 (epidermal growth factor receptor, ErbB2, and ErbB3) in the conjunctival
 epithelium of patients with keratoconjunctivitis sicca. [...] RESULTS:
 Epidermal growth factor receptor staining was observed in a greater
 percentage of keratoconjunctivitis sicca than normal samples (P <.05). [...]
 CONCLUSION: The expression of the type 1 growth factor receptors is
 significantly greater in the conjunctival epithelium of eyes with
 keratoconjunctivitis sicca than normal eyes. The increased expression of
 these receptors was positively correlated with ocular surface dye staining.
 The increased expression of these receptors may contribute to the abnormal
 growth and differentiation of the conjunctival epithelium that occurs in
 keratoconjunctivitis sicca.
 PMID: 10764856, UI: 20229439
----

Purtroppo la cosa è scoppiata in mano a te
Ginzo: non prenderla sul piano personale. Non ho detto "ti scoppiano
in mano" riferendomi a te personalmente. Rileggi bene la frase ed
applicala al genere umano......:-)))
Quando mai a te scoppierebbe qualcosa in mano.....!!! Non mi sarei mai
permesso!  :-))) sei troppo accorto e preciso.
Dovresti però essere aggiornato sulla quantità enorme e smisurata di
stronzate che sono state compiute sull'onda di un entusiasmo
"scientifico" e laboratoristico, presto spento da una realtà
incontrollabile e foriera di disastri. Quando si gioca con peptidi
quasi sconosciuti (ormoni o pseudotali) si sa dove si inizia e non si
sa dove si termina  :-) Era questo il senso della mia frase.
Permalosetto?  :-)))))))
Con stima e simpatia
Stefano Dpkt

diversi errori, e correzioni come le tue non possono che farmi
piacere.
Ti ringrazio della stima e ti sono grato anche perchè, con i tuoi
pungoli, mi stimoli ad approfondire argomenti intelligenti come
questo.  :-))))
Stefano Docpocket

indenne nell'intestino
Se hai letto bene una mia risposta, io riporto lo stesso lavoro nel
mio secondo post (ma senza citarne gli estremi....mea culpa) proprio
per corroborare una mia ipotesi e cioè che l'EGF esogeno (di
derivazione materna e fornito col latte) non abbia funzioni correlate
alla protezione dall'ulcera ma importantissime azioni di stimolo allo
sviluppo della mucosa gastrointestinale (più intestinale che gastrica)
in funzione della loro futura funzione digestiva nei confronti di
alimenti più complessi del latte.
Dpkt:>> Carcinoma METASTATICO....., non primitivo  :-)))
Ginzo:>Appunto: non è stata l'urina dell'urinoma a provocarlo.
Devo essermi espresso male, scusami. Quello che intendevo dire col mio
laconico commento è che quando si pubblica un case report si vuole
sottolineare proprio la "stranezza" dell'evento, non la sua norma. In
pratica si denuncia una "singolarità" in deroga ad una norma che è ben
differente  :-)))
Stima  :-)))
Docpocket

> studiarlo bene e non giocarci  troppo. Mi da l'idea di una di
quelle cose che, se >>maneggiate con troppa disinvoltura, ti scoppiano
in mano
Ribadisco  :-))))
Inoltre aggiungo (ad esplicazione dell'ultima frase da cui ti sei
sentito colpito): "ho la sensazione che sia una di quelle cose che il
"genere umano", in caso di incauto uso, potrebbe pagare cara in
termini di possibili conseguenze sull'equilibrio dell'organismo".
Cosě credo vada un pň meglio  :-))))
Stima
Stefano Docpocket

   -= Ginzo =-
Ciao
Mariano
PS: visto che siamo pochetti ad usare un mac volevo chiederti:
come vedi le lettere accentate degli amici Piccisti che usano Outlook 
Express. Io da cani :((
Rinnovo i miei saluti: "An Apple a day keeps ... away" [for the rest of us] 
;)

 Rinnovo i miei saluti: "An Apple a day keeps ... away" [for the rest of us]
Ma quando arriverà il MacOS X, gliela faremo vedere noi ai windowisti!!
(già stangati dalla sentenza antitrust del giudice americano Jackson).
By the way, se ti interessa la gestione di studio medico in ambito Mac,
l'ideale è farla con FileMaker Pro 5, per cui ti consiglio di iscriverti
alla mailing list di  
http://www.fmp.it/
  (ci sono molti medici lì).
Saluti.
  -= Ginzo =-

per esporne di meno, come già segnalato dallo stesso Docpocket).
Suppongo che questa interessante ipotesi sia tua....ed è piuttosto
suggestiva ed interessante. Il problema sta nel fatto che 'sti
maledetti recettori pare siano una bestia nera e che vengano espressi
in eccesso per "errori" cellulari, non solo per fenomeni correlati
alla protezione degli epiteli.
That's all folks  :-)))
Stefano Docpocket

 non solo per fenomeni correlati alla protezione degli epiteli.
D'accordo.  Nelle trasformazioni neoplastiche e varie altre sindromi
è perfettamente possibile che gli EGF-R siano espressi in eccesso
per errori cellulari anziché in reazione a cambiamenti dell'ambiente.
Tuttavia la cheratocongiuntivite secca è abbastanza comune e insorge
facilmente a seguito di una riduzione del fluido lacrimale, per cui
in questi casi è lecito ritenere che l'iperespressione di EGF-R sia
l'effetto e non la causa.  Riporto un ottimo review su lacrime, KCS,
sindrome di Sjogren, videoterminali, e importanza di EGF e vit. A:
  [1f] Prog Retin Eye Res 1998 Oct;17(4):565-96
 Tear dynamics and dry eye.
 Tsubota K
 Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.
 
ka...@eyebank.or.jp
  Tears undergo four processes: production by the lacrimal gland,
 distribution by blinking, evaporation from the ocular surface and drainage
 through the nasolacrimal duct. Abnormalities in any of these steps can cause
 dry eye. There are two kinds of tear production, basic and reflex, which can
 be distinguished from each other by the Schirmer test with nasal stimulation.
 Reflex tearing is important because it supplies such essential components
 as EGF and vitamin A, whose deficiency may cause squamous metaplasia.
 There is no reflex tearing in Sjogren's syndrome because of destruction of
 the lacrimal gland. In cases of diminished or absent reflex tearing, topical
 autologous serum is the treatment of choice. Even when there is adequate
 tear production, insufficient distribution, such as occurs with the decreased
 blinking associated with the use of video display terminals (VDT), may cause
 dry eye. Any process or activity that suppresses blinking interferes with
 tear distribution. Tear evaporation increases under certain conditions and
 in some diseases. When the exposed ocular surface area is increased, such
 as in VDT work, tear evaporation increases. Meibomian gland dysfunction (MGD)
 also causes increased tear evaporation by altering the quality of the oily
 layer in tears. Tear evaporation can be suppressed by using a warm compresser
 or a humidifier, narrowing the palpebral fissure, or wearing protective
 eyeglasses. The tear clearance rate is measured by fluorescein dye dilution
 in the conjunctiva. When the tear clearance is low, inflammatory cytokines
 or preservatives accumulate in the conjunctival sac, resulting in ocular
 surface diseases. Frequent use of artificial tears without preservative is
 the key treatment. A differential diagnosis of the abnormalities of tear
 dynamics can give us a proper understanding of the pathogenesis of dry eye.
 With this knowledge, we can formulate an efficient therapeutic approach.
 PMID: 9777650, UI: 98450825
E` molto interessante notare che l'anno scorso sono già state condotte
delle sperimentazioni cliniche instillando negli occhi siero autologo
(che dovrebbe contenere circa 1,5 ng/ml di EGF, concentrazione molto vicina
a quella dell'EGF nel fluido lacrimale) e i risultati sono stati molto buoni
anche nella sindrome di Sjogren, già dopo un mese di trattamento:
  [2f] Br J Ophthalmol 1999 Apr;83(4):390-5
 Treatment of dry eye by autologous serum application in Sjogren's syndrome.
 Tsubota K, Goto E, Fujita H, Ono M, Inoue H, Saito I, Shimmura S
 Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.
  AIM: To evaluate the efficacy of autologous serum application for the
 treatment of dry eye in Sjogren's syndrome. METHODS: The stability of
 essential components (EGF, vitamin A, and TGF-beta) in preserved serum
 were examined following preservation at 4 degrees C and -20 degrees C.
 In a primary clinical trial, 12 patients with Sjogren's syndrome were
 treated with autologous serum (diluted to 20% with sterile saline) for
 4 weeks, and vital staining of the ocular surface was compared before
 and after treatment. The effects of serum on mucin (MUC-1) expression
 were observed in cultured conjunctival epithelial cells in vitro.
 RESULTS: EGF, vitamin A, and TGF-beta were well preserved for up to 1 month
 in the refrigerator at 4 degrees C and up to 3 months in the freezer at
 -20 degrees C. Rose bengal and fluorescein scores improved significantly
 from the initial scores of 5.3 and 5.6 to 1.7 and 2.5 after 4 weeks,
 respectively. The additive effect of human serum for cultured conjunctival
 epithelial cells showed significant MUC-1 upregulation on the cell surface.
 CONCLUSION: Autologous serum application is a safe and efficient way
 to provide essential components to the ocular surface in the treatment
 of dry eye associated with Sjogren's syndrome.
 PMID: 10434857, UI: 99363715
  [3f] Ophthalmology 1999 Oct;106(10):1984-9
 Treatment of persistent corneal epithelial defect by autologous serum
 application.
 Tsubota K, Goto E, Shimmura S, Shimazaki J
 Department of Ophthalmology and Oral Health Center, Tokyo Dental College,
 Ichikawa-shi, Chiba, Japan. 
ka...@eyebank.or.jp
  OBJECTIVE: To evaluate the efficacy of autologous serum application
 for the treatment of persistent epithelial defect. DESIGN: Prospective,
 clinical, noncomparative case series. PARTICIPANTS: A total of 16 eyes were
 studied. INTERVENTION: Autologous serum was prepared from the patients and
 diluted to 20% by saline. The patients were instructed to use the autologous
 serum six to ten times a day. The concentration of vitamin A, epidermal
 growth factor (EGF), and transforming growth factor-beta (TGF-beta) was
 measured at 1 week and 1 month stored in the refrigerator and 1 month
 and 3 months in the freezer. MAIN OUTCOME MEASURES: Time to closure of
 epithelial defect. RESULTS: Vitamin A, EGF, and TGF-beta were stable
 during the 1 month in the refrigerator and 3 months in the freezer.
 Among 16 persistent epithelial defects, 7 (43.8%) healed within 2 weeks,
 3 (18.8%) healed within 1 month, and the remaining 6 (37.5%) did not respond
 within 1 month. No apparent side effect of autologous serum application
 was observed. CONCLUSIONS: Autologous serum application healed 43.8%
 of persistent defect within 2 weeks and 62.5% within 1 month.
 PMID: 10519596, UI: 99447085
La mia ipotesi è dunque che, se si può impiegare il siero per apportare
l'EGF, in teoria si potrebbe impiegare anche l'urina (che presenta minori
difficoltà di ottenimento) opportunamente diluita (non è un problema,
visto che la concentrazione dell'EGF nell'urina è molto più alta che
nel siero o nelle lacrime).  La diluizione permette di portare l'urina
all'osmolarità adeguata, pur mantenendo un elevato contenuto di EGF.
Rimane il fatto che l'urina non contiene vit. A che in tracce, a meno
che uno non ne assuma megadosi, oppure abbia un'infezione febbrile:
  [4f~] Am J Clin Nutr 1994 Sep;60(3):388-92
 Vitamin A is excreted in the urine during acute infection.
 Stephensen CB, Alvarez JO, Kohatsu J, Hardmeier R, Kennedy JI Jr,
 Gammon RB Jr
  [...] We have found, however, that significant amounts of retinol and
 retinol-binding protein (RBP) were excreted in the urine during serious
 infections, whereas only trace amounts were found in the urine of healthy
 control subjects. [...] These data show that vitamin A requirements are
 substantially increased during serious infections because of excretion of
 retinol in the urine, and suggest that these losses are due to pathologic
 changes associated with the febrile response.
 PMID: 8074070, UI: 94354145
In conclusione, a mio parere non è assurdo pensare che qualche volta
l'urinoterapia oftalmica (limitatamente all'occhio secco) possa avere
effettivamente funzionato.  Varrebbe quindi la pena di studiare con più
attenzione la cosa, perché la concentrazione e la quantità totale di EGF
nell'urina appaiono molto interessanti.
Saluti.
  -= Ginzo =-

Veramente complimenti a tutti... sono al 3 anno di medicina, appena entrato
nel mondo delle news, e ho trovato i vostri interventi davvero fantastici,
mi chiedo solo dove troviate il tempo per essere sempre così documentati...
a proposito di tempo, mi tocca tornare a studaire, cmq preferisco di gran
lunga seguire i vostri interventi piuttosto che i noiosissimi libri di
testo.... un saluto a tutti
Green

 testo....
Non mi sembra una buona idea per il tuo successo negli studi!  Piuttosto,
se trovi che i tuoi testi siano noiosissimi, è probabile che ne esistano
altri molto più validi sul piano didattico... ad esempio, se stai studiando
patologia generale, dai un'occhiata a questo testo:
  A. Stevens, J. Lowe
  Patologia
  Ed. CEA 1997
  ISBN 88-408-0927-9
  L. 92.000
Se, dopo averlo esaminato, definirai "noiosissimo" anche questo testo,
allora vuol dire che hai sbagliato facoltà...
Bye,
  -= Ginzo =-

 
[...]
Hai letto Beggars in Spain?
li ipotizza il contrario:
gli "Insonni" campano piů a lungo....
-- 
 _______     _______
(-_-<_  \   /  _>-_-)
   -_-<_ \ / _>-_-
       GioVanni-  Caluri
Giovann...@CSELT.SFILAMI.IT
http://www.pegacity.it/parco/abita/280/index.htm
SFILARE .SFILAMI che e` li per gli spammers

 gli "Insonni" campano piů a lungo....
Non l'ho letto.  Ma č un romanzo?  Se sě, non mi sembra serio
citare un romanzo come referenza in un thread su ISM.
Bye,
  -= Ginzo =-