bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of the Depigmenting Effect of Hydroquinone and 4-Hydroxyanisole by All-Trans-Retinoic Acid (Tretinoin): The Impairment of Glutathione-Dependent Cytoprotection?
Authors: Kasraee Behrooz , Handjani Farhad , Aslani Fatemeh S.
Published: May 2003

Many of the well-known depigmenting agents such as hydroquinone and 4-hydroxyanisole are, in fact, melanocytotoxic chemicals which are oxidized in melanocytes to produce highly toxic compounds such as quinones. These cytotoxic compounds are responsible for the destruction of pigment cells, which results in skin depigmentation. However, cells are capable of protecting themselves against cytotoxic agents by intracellular glutathione (GSH). This protection takes place under the enzymatic action of the detoxification enzyme glutathione S-transferase (GST), which is responsible for the conjugation of toxic species to GSH. The depigmenting effect of hydroquinone is shown to be potentiated by buthionine sulfoximine (BSO) and cystamine as the result of the reduction of intracellular levels of GSH by these two agents. Additionally, BSO and cystamine are shown to inhibit the activity of GST. The combination of all-trans-retinoic acid (tretinoin, TRA) with hydroquinone or 4-hydroxyanisole is also known to produce synergetic skin depigmentation. TRA serves as a potent inhibitor of mammalian GSTs and is known to make cells more susceptible to the cytotoxic effect of chemicals by inhibiting the activity of this enzyme. This agent is also shown to reduce the level of intracellular GSH in certain cells. We have proposed that the mechanism of action of TRA to synergistically enhance the melanocytotoxic effect of chemicals involves the inhibition of GST and the impairment of glutathione-dependent cytoprotection against melanocytotoxic agents.
Effect of Lesion Size on the Diagnostic Performance of Dermoscopy in Melanoma Detection
Authors: Carli Paolo , De Giorgi Vincenzo , Chiarugi Alessandra , Nardini Paolo , Mannone Francesca , Stante Marcello , Quercioli Elena , Sestini Serena , Giannotti Benvenuto
Published: May 2003

Background: Dermoscopy is able to correctly classify a higher number of melanomas than naked-eye examination. Little is known however about factors which may influence the diagnostic performance during practice. The aim of the study was to analyze the effect of size of the lesion on diagnostic performance of dermoscopy in melanoma detection. Methods: Eight dermatologists examined clinical and, separately, clinical and dermoscopic (combined examination) images of 200 melanocytic lesions previously excised [64 melanomas, 24 in situ and 40 invasive (median thickness 0.30 mm) and 136 melanocytic nevi]. After examination, diagnostic performance was analyzed in accordance with the major diameter of the lesions divided into 3 groups, i.e. small (less than 6 mm), intermediate (between 6 and 9 mm) and large (10 mm or more) lesions. These groups were shown to be highly comparable concerning the microstaging of melanomas (median thickness value 0.30, 0.22 and 0.32 mm, respectively). Results: Dermoscopy increased the diagnostic performance of naked-eye examination of both intermediate and large lesions [sensitivity value: +19.3 (p = 0.002) and +10.3 (p = 0.007); diagnostic accuracy value: +7.4 (p = 0.004) and +6.1 (p = 0.07)]. On the contrary, no statistically significant increase was found dealing with small lesions (sensitivity +3.7, p = 0.66; diagnostic accuracy –1.7, p = 0.55). Conclusions: The diagnostic improvement associated with the addition of dermoscopy to naked-eye examination is influenced by the size of the lesion, i.e. it is lacking with lesions up to 6 mm in diameter. The optimized use of dermoscopy in melanoma detection is obtained dealing with melanocytic lesions 6 mm in diameter or larger.
Association of Urticaria pigmentosa with Café-au-Lait Spots, Neurofibromas and Neurofibroma-Like Neoplasms: A Mere Coincidence?
Authors: Möhrenschlager Matthias , Engst Reinhard , Müller-Weihrich Stefan , Spiessl Walter , Rüdisser Klaus , Weigl Lorenz B. , Jessberger Berthold , Braun-Falco Markus , Abeck Dietrich , Ring Johannes
Published: May 2003

Background: Urticaria pigmentosa (UP) is characterized by dense aggregates of mast cells in the dermis. There is consistent evidence from the literature that mast cells may play a pathogenetic role in the development of neurofibromas and other tumors. Objective: To study the concomitant appearance of UP with neurofibromas and neurofibroma-like neoplasms. Methods: We analyzed 31,752 records of patients examined at the Department of Dermatology in the year 2000, looking for UP and associated neurofibromas and neurofibroma-like neoplasms in persons younger than 18 years. Results: We identified a total of 27 patients suffering from UP, with 16 persons younger than 18 years. One 12-year-old Caucasian boy demonstrated multiple cutaneous mastocytomas consistent with the diagnosis of UP. On his trunk, four café-au-lait spots were found. A cutaneous neurofibroma was confirmed by skin biopsy. Magnetic resonance imaging detected multiple neoplasms located at the nerve roots of the spine, resembling plexiform neurofibromas. Conclusions: There may be a concomitant appearance of UP and neoplasms, with mast cells possibly playing a causative role. The existence of neoplasms, including neurofibromas and neurofibroma-like lesions should be considered when examining UP cases.
A Randomized, Double-Blind, Placebo-Controlled Trial of Vitamin C Iontophoresis in Melasma
Authors: Huh Chang-Hun , Seo Koo-Il , Park Je-Young , Lim Jeong-Gu , Eun Hee-Chul , Park Kyung-Chan
Published: May 2003

Background: Vitamin C is known to both inhibit melanin formation and reduce oxidized melanin. However, vitamin C does not easily penetrate the skin. In this study, vitamin C iontophoresis was employed in order to enhance vitamin C penetration. Objective: The purpose of this study was to evaluate the efficacy of vitamin C iontophoresis for melasma patients. Methods: Twenty-nine females with melasma were enrolled. For iontophoresis, a vitamin C solution was applied to one side of the face, while distilled water was applied to the other side as a control. The L (luminance) value was measured by a colorimeter to obtain an objective pigmentation parameter. Results: Twelve weeks after iontophoresis, the colorimeter of the treated site showed a significant decrease in the L value (from 4.60 to 2.78, p = 0.002), compared to that of the control site (from 4.45 to 3.87, p = 0.142). Conclusion: Vitamin C iontophoresis may be an effective treatment modality for melasma.
Type 2 Segmental Manifestation of Congenital Multiple Glomangiomas
Authors: Allombert-Blaise Carole Jouffrey , Batard Marie-Laure , Ségard Magali , Martin de Lassalle Elisabeth , Brevière Georges-Marie , Piette Frédéric
Published: May 2003

Congenital multiple glomus tumors are extremely rare, and less than 20 cases have been well documented. We report an uncommon case of congenital multiple glomangiomas with a segmental manifestation in a 9-year-old girl. Since birth, the child had presented asymptomatic angiomatous macules arranged in a segmental pattern on the neck and trunk. During a follow-up period of 9 years, disseminated smaller papulonodular lesions developed on both arms and the left leg with a segmental distribution. Histopathology of congenital and acquired lesions confirmed the diagnosis of glomangiomas. The family history was negative for glomus tumors. This type of presentation supports the recently described type 2 segmental manifestation of multiple glomus tumors, with a segmental involvement of congenital early developing lesions.
Recurrent E413K Mutation of hHb6 in a Japanese Family with Monilethrix
Authors: Muramatsu Shigenori , Kimura Tami , Ueki Rie , Tsuboi Ryoji , Ikeda Shigaku , Ogawa Hideoki
Published: May 2003

Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair due to periodic thinning of the shaft. This disorder has been reported to be caused by mutations in the helix termination motif of two type II cortex keratins, hHb1 and hHb6. Here we describe a Japanese monilethrix family that has the most frequent mutation, the E413K mutation in hHb6, so far found in 26 families. Genotype/phenotype correlation was not obvious in our case or in the previously reported cases.
Nail Destruction in Pemphigus vulgaris
Authors: Kolivras A. , Gheeraert P. , André J.
Published: May 2003

Involvement of the nails in pemphigus vulgaris (PV) is rare and is usually seen when the disease is severe. The most common clinical manifestations are chronic paronychia and onychomadesis. Finger nails are more frequently involved than toe nails. We report a case of severe and persistent PV in which an exacerbation was preceded by an erosive and destructive lesion of the right hallux nail unit. A nail bed biopsy was performed to rule out a subungual tumour. The image of suprabasal acantholysis yielded the diagnosis of PV. This localisation and clinical manifestation of PV have only been reported once.
Histometric Assessment of Psoriatic Plaques Treated by Vitamin D3 Derivatives
Authors: Uhoda Isabelle , Quatresooz Pascale , Hermanns-Lê Trinh , Piérard-Franchimont Claudine , Arrese Jorge E. , Piérard Gérald E.
Published: May 2003

Background: Psoriasis is an immunogenetic disorder. Factor XIIIa+ dermal dendrocytes (DD) are part of the pathobiological changes in the plaque type of the disease. Objective: The present study aimed at comparing the effect of 3 vitamin D3 derivatives on the epidermis, microvasculature and DD in psoriasis. Method: Twenty men suffering from chronic plaques of psoriasis on the trunk were enrolled in this study. They applied twice a day for 3 weeks calcipotriol, tacalcitol and calcitriol, each to one plaque. Another similar lesion received petrolatum as a placebo treatment. Skin biopsies were taken at entry and at completion of the 3-week treatment phase. Immunohistochemistry was performed using the lectin of Ulex europaeus and an antibody to factor XIIIa. Computerized image analysis served to measure the stratum Malpighii area, the microvasculature area and the DD numerical density in the papillary dermis. Results: At entry in the study, the 4 test sites were indistinguishable with regard to the stratum Malpighii area, the papillary microvasculature area and the papillary DD density. The 3 histometric parameters appeared correlated with each other. At completion of the 3-week treatment phase, the 3 vitamin D derivatives had decreased the size of the stratum Malpighii. In addition, calcitriol had also reduced the DD density in the papillary dermis. No other significant changes were yielded. Conclusion: As assessed by histometry, the psoriatic epidermis responded to a short treatment using the 3 vitamin D derivatives. The better result compared to the control site was achieved by calcitriol. DD appeared to be most controlled by the same drug. The microvasculature did not appear to be decreased at the 3-week time point in treatment.
Two Cases of Cross-Sensitivity in Subjects Allergic to Paraphenylenediamine following Ingestion of Polaronil®
Authors: Sornin de Leysat C. , Boone M. , Blondeel A. , Song M.
Published: May 2003

We report the cases of 2 women presenting allergy to paraphenylenediamine (PPD). Both patients had a history of eczema that worsened following the ingestion of the antihistamine Polaronil® (dexamethasone/dexchlorpheniramine). This clinical presentation could be explained by cross-sensitivity to sulfanilic acid (4-aminobenzene sulfonic acid), a metabolite of sunset yellow (FD&C No. 6). Sunset yellow is an azo dye present in this tablet. Indeed, PPD-allergic subjects may suffer from cross-sensitivity to related compounds, especially to those that can be ingested such as azo dyes. Such compounds are used in some instances by the food and pharmaceutical industries, but their presence is often undisclosed.
Adverse Skin Reactions to Anti-TNF-Alpha Monoclonal Antibody Therapy
Authors: Devos S.A. , van den Bossche N. , De Vos M. , Naeyaert J.M.
Published: May 2003

Various adverse cutaneous reactions to anti-TNF-α monoclonal antibody have been reported. In clinical studies with infliximab (Remicade®) adverse drug reactions were most frequently reported in the respiratory system and in the skin and appendages. We describe here 6 patients receiving anti- TNF-α therapy (infliximab) for Crohn’s disease or rheumatoid arthritis who consulted our out-patient department for adverse cutaneous reactions between November 1999 and February 2002. The following diagnoses were made: leukocytoclastic vasculitis, lichenoid drug reaction, perniosis-like eruption (2 patients), superficial granuloma annulare and acute folliculitis.
Lassueur-Graham Little-Piccardi Syndrome: A 20-Year Follow-Up
Authors: Ghislain Pierre-Dominique , van Eeckhout Pascal , Ghislain Emile
Published: May 2003

Lassueur-Graham Little-Piccardi (LGLP) syndrome is a distinctive entity associating a scarring patchy alopecia of the scalp, a non-cicatricial axillary and pubic hair loss and a lichenoid follicular eruption. We present a 20-year follow-up of a demonstrative case, which had begun as typical lichen planus. In the literature, the relationship with lichen planus remains unclear. The diagnosis of LGLP syndrome should be evoked for all scarring alopecias.
Granulomatous Slack Skin: Treatment with Extensive Surgery and Review of the Literature
Authors: Clarijs Magali , Poot Françoise , Laka Andoni , Pirard Christian , Bourlond André
Published: May 2003

We report an 11-year follow-up of a case of granulomatous slack skin. The patient was first treated surgically followed by a rapid relapse. Then he was treated by α-interferon during 15 months. When this treatment was stopped, the disease relapsed again. Extensive surgery was undertaken. Recently, a new relapse has occurred which was again treated by extensive surgery. No other manifestation of a lymphoproliferative disorder appeared. The clinical, histological, immunohistochemical, ultrastructural, molecular biological and genetic studies with a review of 39 other cases described in the literature are presented.
Brain Activation of Monocyte Lineage Cells: Brain-Derived Soluble Factors Differentially Regulate BV2 Microglia and Peripheral Macrophage Immune Functions
Authors: Shafer Lisa L. , McNulty John A. , Young M. Rita I.
Published: May 2003

Brain injury and subsequent neurodegeneration are often associated with infiltrating leukocytes and the activation of microglia as well as other infiltrating cells. However, the characteristics of activation are poorly understood. The objective of this study was to further the understanding of brain regulation of microglial activation. We used an organotypic coculture paradigm to assess how brain-derived soluble factors modulate microglia and peripheral macrophage activation through microscopy and flow cytometry techniques. In the presence of brain-derived soluble factors, the BV2 microglia cell line increased MHC II and phagocytic receptor (Fcγ II/III) expression. The increased expression correlated with a functional increase in phagocytic activity, but did not correlate with an increase in allostimulation ability. Furthermore, this interaction was selective to an interaction between brain-derived soluble factor(s) and BV2 microglia, since it was not observed in the ANA1 macrophage cell line or in primary peritoneal macrophages. The results indicated that brain-derived soluble factor(s) modulate microglial activation in a manner that is distinct from the effects on peripheral macrophages. Moreover, our results suggest that inflammatory events associated with some types of brain injury may be induced by the brain without dependence on infiltrating peripheral macrophages or T lymphocytes.
Time Delay as a Parameter for Cerebrovascular Reactivity in Patients with Severe Carotid Stenosis
Authors: Hetzel A. , Guschlbauer B. , Reinhard M.
Published: May 2003

Background: Amplitude responsiveness of cerebral blood flow velocity (CBFV) to CO2 is an established test of cerebrovascular reserve capacity. We aimed to analyze the time course of CBFV during CO2 reactivity testing in patients with severe carotid stenosis. Methods: 87 patients were assigned to three different groups according to the degree of stenosis (A 75–89%, B 90–94%, C 95–100%) and CBFV dynamics was assessed by transcranial Doppler sonography during hypercapnia induced by inhalation of 7% CO2. Time constants for the duration of CBFV and the end-tidal CO2 partial pressure (PetCO2) increase and decrease were calculated. In addition, time delays between subsequent changes of PetCO2 and CBFV during on- and offset of hypercapnia were determined. Results: There was a significant reduction of conventional CO2 reactivity on the side ipsilateral to the stenosis in all groups. Time constants of CBFV showed no major differences between ipsi- and contralateral sides or between different groups. The off delay between the decrease in PetCO2 and the consequent decrease in CBFV was the only out of 6 different dynamic parameters which significantly differentiated critical stenosis and occlusion from severe stenosis. Retest variability showed a highly significant correlation. Conclusions: Analysis of the dynamic CBFV response during the applied CO2 inhalation protocol revealed a significant and reproducible delay parameter which has power to detect cerebral hemodynamic compromise in patients with carotid artery stenosis similar to the conventional CO2 reactivity parameter.
The Role of Blood Pressure in Lacunar Strokes Preceded by TIAs
Authors: Lalive P.H. , Mayor I. , Sztajzel R.
Published: May 2003

Lacunar strokes (LS) are often preceded by repetitive transitory ischaemic attacks (TIAs) known as ‘capsular warning syndrome’. The treatment of these symptoms remains controversial. Anticoagulants are often used in this situation, most of the time, however, with no or little benefit. Since it is not rare that these TIAs lead to a definite stroke, the therapeutic approach in the acute phase is very important. We report six patients presenting LS preceded by TIAs. All patients showed intermittent decrease of blood pressure (BP) coinciding with clinical worsening and leading to definite stroke in four of them. All were treated with full-dose intravenous heparin, which did not prevent further clinical deterioration. One patient received noradrenalin, which allowed stabilisation of the blood pressure values and complete resolution of the neurological symptoms. This observation suggests that in lacunar strokes preceded by TIAs monitoring and, if necessary, pharmacological increase of BP may prevent some patients from developing a definite stroke. Thus the ‘capsular warning syndrome’ could reflect a haemodynamic failure rather than repeated thrombo-embolism within the lumen of a single perforating arteriole.
Alteration of α1A-Adrenoceptor Gene Expression in the Prostate of Streptozotocin-Induced Diabetic Rats
Authors: Tong Yat-Ching , Liu I-Min , Cheng Juei-Tang
Published: May 2003

Diabetes-associated alterations in prostate α1A-adrenoceptor (α1A-AR) gene expression were studied using a streptozotocin (STZ) induced diabetic rat model. Male Wistar rats were divided into four groups: group I animals were vehicle-treated normal rats; group II consisted of vehicle-treated, STZ-diabetic rats; group III represented insulin-treated, STZ-diabetic rats (0.5 IU/kg three times daily for 4 days), and group IV animals were phlorizin-treated, STZ-diabetic rats (1 mg/kg three times daily for 4 days). The expression of mRNA that encoded protein of α1A-AR in the rat prostate was studied using reverse transcription combined with polymerase chain reaction. The α1A-AR protein expression in the prostate was studied by Western blotting analysis with a polyclonal antiserum. A 2.51 ± 0.21-fold increase in the mRNA level of α1A-AR was observed in the prostate of diabetic rats (n = 8, p < 0.05). Similarly, there was a 2.23 ± 0.10-fold increase in the α1A-AR protein level (n = 8, p < 0.05). Both insulin and phlorizin treatments restored the normal levels of mRNA and protein expression. In conclusion, the gene expression of α1A-AR is increased in the prostate of diabetic rats. Hyperglycemia plays a major role in this alteration.
Effect of Two Modes of Antiandrogen Treatment on Insulin Sensitivity and Serum Leptin in Women with PCOS
Authors: Krotkiewski Marcin , Landin Kerstin , Dahlgren Eva , Janson Per Olof , Holm Göran
Published: May 2003

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.
GnRH Analogues, Transvaginal Ultrasound-Guided Drainage and Intracystic Injection of Recombinant Interleukin-2 in the Treatment of Endometriosis
Authors: Acién Pedro , Quereda Francisco J. , Gómez-Torres María-José , Bermejo Rosa , Gutierrez Mercedes
Published: May 2003

We performed a double-blind, randomised controlled trial to evaluate the results of ultrasound-guided aspiration of endometriomas under the effect of GnRH analogues and a possible additional beneficial effect by leaving 600,000 IU of recombinant interleukin-2 (rIL-2) in the cysts. Twenty-four women with endometriosis-related symptoms, increased values of CA-125 and transvaginal ultrasonography showing endometriomas >3 cm who were initially sent to us for laparotomy and conservative surgery for endometriosis were included. Main outcome measures were severity of symptoms, size and percentage of echographical reduction of endometriomas and CA-125 levels after 2 menses post-GnRH analogues. Secondary outcome measures were the time until recurrence of abnormal parameters and the need for surgery after treatment. We found moderate clinical results after treatment with drainage plus GnRH analogues and significantly improved results in women having received rIL-2 intracystically. There were no side effects. Two out of 3 previously infertile patients became pregnant after therapy. Though the rates of recurrence of endometriomas ≧3 cm were similar in both groups, the period until recurrence was significantly greater when rIL-2 was used, and the rates of recurrence of symptoms and increased CA-125 values were also significantly lower in patients who received rIL-2. Surgery was finally performed on 10 patients (4 with and 6 without previous rIL-2 treatment) during follow-up (30 ± 12.7 months). These findings led to the conclusion that transvaginal ultrasound-guided puncture and aspiration of endometriomas under endometrial suppressive therapy with GnRH analogues have some value for endometriosis treatment, improving the clinical manifestations and avoiding some surgical therapies, and that rIL-2 left in the cyst increases these beneficial effects significantly.
Laparoscopically Assisted Vaginal Hysterectomy versus Total Abdominal Hysterectomy: A Study of 100 Cases on Light-Endorsed Transvaginal Section
Authors: Tsai Eing-Mei , Chen Hung-Sheng , Long Cheng-Yu , Yang Cheng-Hui , Hsu Shih-Cheng , Wu Chin-Hu , Lee Jau-Nan
Published: May 2003

The objective of this study was to compare the results of a modified laparoscopically assisted vaginal hysterectomy (LAVH) procedure, using light-endorsed transvaginal section by two puncture trocars, with those of total abdominal hysterectomy (TAH) in a prospective, randomized, short-term study. A new, modified LAVH technique using Endo GIA stapler and two puncture trocars was established. For the laparoscopic phase, each adnexum was dissected, and the vesicouterine junction was identified clearly with the laparoscopic light from the vaginal side. Vaginal-phase surgery was performed as usual. Two hundred patients scheduled for abdominal hysterectomy were randomized to either LAVH (n = 100) or TAH (n = 100). Duration of hospitalization, time of surgery, dose of analgesics, and rates of complications were significantly lower in the LAVH group (p < 0.001). The average operating time was 77 ± 30 min for LAVH and 102 ± 18 min for TAH. The duration of hospitalization was 3.2 ± 0.7 days for LAVH and 5.5 ± 1.3 days for TAH. There were three complications in the LAVH group and 15 in the TAH group. Postoperative meperidine requirements (1.2 vs. 3.7 ampoules, 1 ampoule = 50 mg) were significantly fewer in the LAVH group. Regarding the training time, the mean operating time in the first 20 cases was 98 min, and in the last 20 cases it was 70.9 min. As compared with TAH and other modified LAVH procedures reported previously, the present technique is easy to learn and timesaving with fewer complications.
Surface Area of the Human Vagina as Measured from Vinyl Polysiloxane Casts
Authors: Pendergrass Paula B. , Belovicz Meyer W. , Reeves Cornelia A.
Published: May 2003

Sixty-two vinyl polysiloxane casts from subjects in the lying, supine position were measured for surface area with five shapes: conical, parallel sides, heart, slug, and pumpkin seed being included. The surface areas ranged from 65.73 to 107.07 cm2 with a mean of 87.46 cm2 and a standard deviation of 7.80 cm2. There were no significant differences in surface area among the shape groups. And no correlations with surface area were found by parity or by rod length, introital diameter, posterior length of casts as measured with string, or greatest width and greatest depth of casts. 70% of the casts had a surface area of 84.50 cm2 or above, and 90% had a surface area of 77.72 cm2 or above. Variation within the interquartile range (75th to 25th percentile) was ±5.2% of the median.
Vascular Calcification in Chronic Renal Failure
Authors: Tomson Charlie
Published: May 2003

The prevalence and extent of vascular calcification (VC) increases rapidly with time on dialysis. There is increasing evidence that medial calcification of conduit arteries, without intimal disease, is associated with important abnormalities of vascular compliance and increased risk of cardiovascular death. Coronary artery calcification is also common in end-stage renal disease, but further research is required to determine how much of this calcification is in the form of calcified intimal atherosclerotic plaque and how much in the tunica media. Calcific uraemic arteriolopathy causes a syndrome of ischaemic necrosis of the skin and subcutaneous tissue and appears to be increasing in incidence. At all sites, arterial calcification is a biologically controlled process, with expression in vascular smooth muscle cells of genes usually expressed in osteoblasts and the formation of hydroxyapatite. High extracellular phosphate concentration induces these phenotypic changes in vitro, and much of the clinical evidence supports hyperphosphataemia as the major driver of VC. Whether warfarin treatment plays a role, by inhibiting production of vitamin-K-dependent inhibitors of calcification in humans, remains uncertain but possible. High doses of prescribed calcium-based phosphate binders are associated with VC, whereas use of sevelamer to achieve the same serum phosphate level greatly retards progression of coronary and aortic calcification. The biological mechanism by which positive calcium balance and/or episodes of hypercalcaemia promotes VC remains unclear. Treatment of established calcific uraemic arteriolopathy consists of aggressive reduction of serum calcium × phosphate product; the roles of hyperbaric oxygen, steroid therapy, and non-warfarin anticoagulation remain uncertain.
Low Urinary Albumin Excretion in Astronauts during Space Missions
Authors: Cirillo Massimo , De Santo Natale G. , Heer Martina , Norsk Peter , Elmann-Larsen Benny , Bellini Luigi , Stellato Davide , Drummer Christian
Published: May 2003

Background: Physiological changes occur in man during space missions also at the renal level. Proteinuria was hypothesized for space missions but research data are missing. Methods: Urinary albumin, as an index of proteinuria, and other variables were analyzed in 4 astronauts during space missions onboard the MIR station and on the ground (control). Mission duration before first urine collection in the four astronauts was 4, 26, 26, and 106 days, respectively. On the ground, data were collected 2 months before mission in two astronauts, 6 months after in the other astronauts. A total of twenty-two 24-hour urine collections were obtained in space (n per astronaut = 1–14) and on the ground (n per astronaut = 2–12). Urinary albumin was measured by radioimmunoassay. For each astronaut, mean of data in space and on the ground was defined as individual average. Results: The individual averages of 24 h urinary albumin were lower in space than on the ground in all astronauts; the difference was significant (mean ± SD, space and on the ground = 3.41 ± 0.56 and 4.70 ± 1.20 mg/24 h, p = 0.017). Dietary protein intake and 24-hour urinary urea were not significantly different between space and on the ground. Conclusions: Urinary albumin excretion is low during space mission compared to data on the ground before or after mission. Low urinary albumin excretion could be another effect of exposure to weightlessness (microgravity).
Non-Shine-Dalgarno Initiators of Translation Selected from Combinatorial DNA Libraries
Authors: Kolev Vihren , Ivanov Ivaylo , Berzal-Herranz Alfredo , Ivanov Ivan G.
Published: May 2003

In a search for non-Shine-Dalgarno (non-SD) translational initiators, two combinatorial expression libraries (denoted R1 and R2) were constructed containing randomized decanucleotide regions placed at either 6 (R1) or 11 (R2) nucleotides upstream of a modified chloramphenicol acetyltransferase (CAT) gene. To prevent sporadic formation of SD-like sequences the content of G in the randomized region was restricted to 3% only. The two libraries were transformed in Escherichia coli cells and screened for chloramphenicol (Cm) resistance. More than 50 clones capable of tolerating Cm concentrations from 50 µg/ml to more than 800 µg/ml were selected. With few exceptions only, the non-SD sequences found in the Cm-resistant clones did not show any significant homology with other known non-SD initiators or enhancers of translation. Statistical (χ2) analysis of the distribution of nucleotides in the new non-SD translational initiators showed a different pattern from that of the conventional SD sequences. In few of the clones the yield of CAT exceeded that of the referent (SD-containing) construct. The most productive clones carried the decanucleotides ATTTACCTCC, CCAATCTAC, TTCAATATTT, and TATTCCCCCA, and the corresponding yield of CAT obtained with them was 2.70, 2.06, 2.12 and 1.32 times, respectively, higher than that of the SD-bearing construct.
Immobilization of Saccharomyces cerevisiae Cells to Protein G-Sepharose by Cell Wall Engineering
Authors: Andrés Isabel , Zueco Jesús , Parascandola Palma
Published: May 2003

In this work, we explored the possibility of using the targeting of a heterologous protein to the cell wall of Saccharomyces cerevisiae, by fusing it to a cell wall protein, to construct yeast strains whose cells display on their surface proteins that bind to a matrix, so as to achieve the immobilization of the whole cells. With this aim, we created a gene fusion that comprises the region responsible for attachment of a cell wall protein to the cell wall, and the IgG binding region of staphylococcal protein A, and expressed it in the mnn1mnn9 strain of S. cerevisiae. The surface display of the protein A-Icwp fusion protein was positively monitored; however, direct immobilization of the cells on an IgG-Sepharose matrix did not produce the expected results, probably due to the fusion protein not being completely exposed on the surface of the cells. To solve this problem we incubated the cells first with rabbit preimmune serum and then with goat anti-rabbit IgGs, so as to create a complex (yeast cell-protein A-rabbit IgG-goat IgG). Cells treated in this way were successfully immobilized on a protein G-Sepharose matrix, due to the binding properties of goat IgGs to streptococcal protein G.
Early OspA Immune Complex Formation in Animal Models of Lyme Disease
Authors: Schutzer Steven E. , Luan Jennifer
Published: May 2003

Infection with Borrelia burgdorferi, the cause of Lyme disease, has been accompanied by a puzzling delayed antibody (Ab) response to B. burgdorferi antigens (Ags) including the abundant organism-specific outer surface proteins, such as the 31-kD OspA. In humans the response to nonspecific B. burgdorferi Ags has required 3–6 weeks. The response to OspA has rarely been detected by conventional methodology until months after infection, despite demonstrable T cell reactivity. Tick inoculation and low-dose intradermal inoculation animal models have been characterized by a comparable response to OspA. Using more sensitive biotin-avidin immunoblots and immune complex (IC) dissociation techniques, we demonstrated in humans that Ab to OspA is formed early but may remain at low levels or bound in IC. To see if this was a universal biologic response, animal models were analyzed by these methods. The results with mice, monkeys and rabbits show that IC Ab to OspA may be detected at the onset of infection. The data suggest that these animal models may be used to understand the immune response to B. burgdorferi and the pathogenesis of Lyme disease. With attention to unique B. burgdoferi Ags, these results are likely to have both clinical and diagnostic importance.
Repeated Estradiol Treatment Prevents MPTP-Induced Dopamine Depletion in Male Mice
Authors: Ramirez Andres D. , Liu Xingrong , Menniti Frank S.
Published: May 2003

Epidemiological data suggest that the steroid hormone 17β-estradiol plays an important role in protecting the brain from neurodegenerative processes, including that causing the loss of dopamine (DA) neurons in Parkinson’s disease. Determining the mechanisms of neuroprotection in experimental systems may facilitate the development of estrogenic therapies for these diseases. The present study sought to further investigate the mechanism of the neuroprotective effect of 17β-estradiol in a murine model of Parkinson’s disease, i.e. 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal DA depletion. Consistent with previous findings, 17β-estradiol was found to inhibit MPTP-induced DA depletion under a dosing regimen (repeated daily administration) that mimicked physiological levels of the steroid. However, high doses of the steroid administered repeatedly or acutely failed to inhibit toxicity, as did 17α- estradiol. These data suggest that the neuroprotective effect of 17β-estradiol was mediated through an interaction with one of the nuclear estrogen receptors, and is not the result of an antioxidant action. In order to realize the therapeutic potential of the neuroprotective effect of 17β-estradiol for Parkinson’s disease, it will be necessary to identify synthetic estrogen receptor modulators that lack the activity of the steroid on peripheral tissue. In this study, raloxifene failed to mimic the neuroprotective effect of 17β-estradiol against MPTP toxicity. Thus, exploration of new compounds with different pharmacological and/or physiochemical properties is warranted.
Gender Differences in Methamphetamine-Induced mRNA Associated with Neurodegeneration in the Mouse Nigrostriatal Dopaminergic System
Authors: Dluzen Dean E. , Tweed Christopher , Anderson Linda I. , Laping Nicholas J.
Published: May 2003

In this report female and male CD-1 mice were treated with a neurotoxic regimen of methamphetamine (MA) to compare gender differences in striatal dopamine depletion and concordant changes in mRNA markers of the transforming growth factor-β injury response associated with neurodegeneration. Striatal dopamine concentrations of MA-treated female mice were less depleted and significantly greater than that of identically treated males. Associated with this gender difference in striatal dopamine depletion were significantly decreased mRNA levels of plasminogen activator inhibitor-1 and a trend for increased (p = 0.06) mRNA levels of glial fibrillary acidic protein within females. No statistically significant differences between MA-treated female and male mice were obtained in mRNA levels for transforming growth factor-β, transforming growth factor-β type 2 receptor, activin-like kinase-5 or fibronectin. These data demonstrate the presence of changes in two specific molecular markers of the transforming growth factor-β injury response which are in accordance with gender differences in MA-induced striatal dopamine depletion. The results suggest that the neuroprotective advantage displayed by females may in part be related to reductions in the transforming growth factor-β injury response as indicated by decreased mRNA plasminogen activator inhibitor-1 and an increased response of reactive astrocytes which promote neuronal survival as indicated by augmented glial fibrillary acidic protein mRNA levels.
Thyrotropin-Releasing Hormone as a Mediator of the Central Autonomic Pathway Controlling Ovarian Function
Authors: Luza S.M. , Arancibia S. , Venegas M. , Lara H.E.
Published: May 2003

We studied the effect of thyrotropin-releasing hormone (TRH) applied centrally on the sympathetic activity of the ovary in female rats. Intracerebroventricular (i.c.v.) administration of a dose of 25 ng/kg weight produced an increase in noradrenaline (NA) content at the ovary after 5 days of hormone administration. However, higher doses in a range up to 500 ng/kg weight decreased NA content at the ovary. At the celiac ganglia (where the cell bodies of sympathetic neurons projecting to the ovary originate) there was an accumulation of NA in spite of a decrease in tyrosine hydroxylase activity (T-OH). After cold exposure, opposite effects on T-OH activity and no effects on NA in ganglia and in ovary were obtained. Besides, i.v. injection of TRH only induced a decrease in ovarian NA. In contrast to the increase in T3 plasma levels obtained after the cold-stress procedure, none of the i.c.v. doses of TRH used produced changes in T3 plasma levels, strongly suggesting that the effect on sympathetic activity is mediated by a central effect of TRH acting as a putative activator of ovarian sympathetic nerves.
Hormonal Therapy in Postmenopausal Women with Breast Cancer
Authors: Campos Susana M. , Winer Eric P.
Published: May 2003

The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced disease setting, but, at best, there has been a modest impact on survival. Numerous options are now available to provide effective palliation for patients with advanced disease. These options include antiestrogens, pure antiestrogens, aromatase inhibitors and progestins and LHRH agonists. Recently, several studies have reviewed the efficacy of aromatase inhibitors as first-line agents in postmenopausal women. Anastrozole and letrozole have recently been approved as first-line agents in women with metastatic breast cancer. In addition to their role in metastatic breast, trials investigating the potential of aromatase inhibitors in the early breast cancer, both in the adjuvant and neoadjuvant setting are underway.
Primary Lymphoma of Bone – A Retrospective Study
Authors: Stein M.E. , Kuten A. , Gez E. , Rosenblatt K.E. , Drumea K. , Ben-Shachar M. , Zidan J. , Haim N. , Epelbaum R.
Published: May 2003

Objective: This retrospective study describes our experience with the diagnosis, treatment, results and long-term follow-up of primary bone lymphoma (PBL). Patients and Methods: Nineteen patients diagnosed with PBL were reviewed. Seven patients presented with stage IE disease, four with stage IIE (regional lymphadenopathy), and eight with stage IV disease (disseminated bone involvement). Only one stage IV patient exhibited ‘B’ symptoms. The majority (72%) demonstrated diffuse, large cell, B-type lymphoma. All patients were treated with adriamycin-based chemotherapy and consolidation radiotherapy to the primary site (8 patients: early PBL) or the most bulky area (3 patients: stage IV PBL). Results: Ten stage IE/IIE patients are alive with no evidence of disease (NED) and only one died due to metastatic secondary lung cancer while with NED from his PBL. Eight stage IV patients are alive with NED. Median follow-up for all living patients: 77 months. Side effects were mild and did not necessitate delay in treatment. Conclusions: Our departmental policy of treating PBL patients with an anthracycline-based regimen and involved field radiotherapy proved to be successful in achieving excellent long-term, disease-free survival. Phase III randomized, controlled, clinical trials will determine the true role of consolidation radiotherapy in PBL, when considering severe late side effects, including radiation-induced bone tumors.
Biochemotherapy for Metastatic Melanoma with Limited Central Nervous System Involvement
Authors: Boasberg Peter D. , O’Day Steven J. , Kristedja Tim S. , Martin Maureen , Wang Hejing , Deck Regina , Shinn Kelly , Ames Pat , Tamar Beth , Petrovich Zbigniew
Published: May 2003

Objectives: Biochemotherapy outcomes were examined in stage IV melanoma patients with previously treated or active central nervous system (CNS) metastases prior to systemic therapy. Patients and Methods: Patients who received biochemotherapy for metastatic melanoma with active or pretreated CNS metastases were compared to patients without evidence of CNS metastases in terms of response, time to progression (TTP), overall survival (OS), and treatment toxicity. Results: Twenty-six (16%) of 159 total patients began biochemotherapy with previously treated or active CNS metastases (group I), compared to 133 (84%) who were radiographically free of CNS involvement (group II). A partial or complete response to biochemotherapy was seen in 13 (50%) group I patients, compared to 56 (42%) group II patients (p = 0.243). The median TTP and median survival were 5.5 and 7.0 months, respectively, for group I patients and 6.0 and 9.9 months, respectively, for group II patients (p = 0.222 and 0.434 for TTP and OS, respectively). Five (19%) group I patients survived longer than 24 months. Gamma Knife radiosurgery or surgical resection of CNS disease prior to biochemotherapy improved survival versus delayed treatment (p = 0.017 and 0.005, respectively). Conclusion: Patients with limited CNS metastases and widespread systemic disease can achieve prolonged survival with targeted treatment of CNS lesions and aggressive systemic therapy.
Subcutaneous Granulocyte-Macrophage Colony-Stimulating Factor in Mucositis Induced by an Adjuvant 5-Fluorouracil plus Leucovorin Regimen
Authors: Rossi Antonio , Rosati Gerardo , Colarusso Diodoro , Manzione Luigi
Published: May 2003

Objective: To test the activity of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) administration in patients with colorectal cancer treated with adjuvant 5-fluorouracil (5-FU) plus leucovorin (LV) and suffering from mucositis. Methods: Thirty-one patients treated with adjuvant 5-FU 370 mg/m2 and LV 100 mg/m2 for 5 days every 4 weeks and reporting grade ≧2 mucositis participated in the study. Subcutaneous GM-CSF 4 µg/kg/day from days 6 to 10 was administered without chemotherapy dose reductions in the cycle that followed the cycle during which mucositis was reported. The disappearance of mucositis or a decrease by ≧1 grade was recorded as a therapeutic success. Baseline toxicity was: grade 2 stomatitis in 12 patients and grade 3 in 9; grade 4, 3 and 2 diarrhoea in 1, 4 and 8 patients, respectively. Results: Seventy-seven GM-CSF cycles were administered. A success was achieved in 20 (64.5%) patients. The efficacy was assessable in 5 (16.1%) patients with grade 2 and in 8 (25.8%) with grade 3 stomatitis, respectively, as well as in 1 (3.2%) and 5 (16.1%) patients with grade 3 and 2 diarrhoea, respectively. Success (3.2%) was reported in 2 patients suffering from both grade 2 stomatitis and diarrhoea. In 7 (22.5%) patients there was no evidence of efficacy. In 4 (12.9%) patients the treatment was stopped after the first administration of GM-CSF due to a grade 2 allergic reaction. Conclusions: The subcutaneous administration of GM-CSF relieved patients from symptoms of 5-FU/LV-induced mucositis with acceptable side effects permitting the maintenance of full-dose chemotherapy.
Ovarian Sertoli-Leydig Cell Tumor, Endometrioid-Like Yolk Sac Tumor, and Y-Chromosomal Material
Authors: De Giorgi Ugo , Turci Daniele , Crisanti Emilia , Cantù Maria Grazia , Cappellini Anna , Marangolo Maurizio
Published: May 2003

Sertoli-Leydig cell tumors (SLCTs) are rare neoplasms, accounting for less than 0.2% of ovarian tumors. The endometrioid-like variant of yolk sac tumor (YST) is very rare, and the most extensive series reported only 8 cases. We present a case of ovarian SLCT with endometrioid-like YST in a patient with a 46,XX karyotype with Y-chromosomal material. A 26-year-old woman had undergone a right salpingo-oophorectomy for SLCT with endometrioid-like YST. Chromosomal analysis revealed a 46,XX karyotype with Y-chromosomal material insertion into chromosome 1. The patient’s father and sister, and 7 other paternal relatives (4 male and 3 female) presented the same chromosome variant without evidence of cancer. The YST component relapsed to the right side of the uterine wall and then metastasized to the peritoneum and liver, while SLCT was eradicated with primary surgery. Several chemotherapeutic regimens were totally ineffective to control tumor progression. She died of disease progression 54 months after the diagnosis. We adopted the policy of a close surveillance for ovarian neoplasms for the 22-year-old sister of the patient, who presented the same Y-chromosomal material in her karyotype. In very rare tumors, new methods, based on molecular and cytogenetic models, are requested to define recommended management.