bluuebunny/crossref_metadata_2025_split huggingface dataset:
FUNCTIONS OF THE RENIN‐ANGIOTENSIN SYSTEM DURING DEVELOPMENT
Authors: Lumbers E. R. 
Published: June 2007

SUMMARY1. From studies in chronically catheterized fetal sheep and other species, it can be shown that the renin‐angiotensin system (RAS) is active during intra‐uterine life. Levels of angiotensin II (AII) in fetal sheep are similar to maternal.2. The fetal RAS plays a role in maintenance of arterial pressure. The extent to which it does so depends on the level of activity of the system.3. The distribution of renin within the fetal rat kidney is much more widespread than in the adult. The fetal kidney, like other vascular beds has high levels of the AT2 angiotensin receptor subtype. With maturation the proportion of the AT1 receptor subtype increases.4. Blockade of the fetal RAS with angiotensin converting enzyme (ACE) inhibitors or with the non‐peptide AII antagonist (losartan) caused a fall in fetal glomerular filtration rate (GFR) and a rise in renal blood flow (RBF). AII reverses the fall in GFR even though RBF decreases.5. The fraction of the filtered sodium load reabsorbed by the proximal tubule was not affected when the fetal RAS was blocked by captopril or losartan. High doses of infused AII had no effect on renal reabsorption of sodium, in the short term, but in the long term depressed fractional proximal reabsorption.6. Only in high doses does AII stimulate the secretion of aldosterone from the fetal adrenal.7. Since the fetal RAS is responsible for maintenance of GFR and physiological levels of AII do not stimulate either proximal tubular sodium reabsorption nor aldosterone secretion, it is proposed that during intra‐uterine life the fetal RAS maintains the renal excretion of sodium and water into the amniotic cavity, thus ensuring an adequate volume of amniotic fluid for normal growth and development.
HYPOXIC INHIBITION OF BREATHING AND MOTOR ACTIVITY IN THE FOETUS AND NEWBORN
Authors: Walker David W. 
Published: June 2007

SUMMARYIn fetal animals hypoxia of rapid onset causes cessation of breathing movements, electro‐ocular activity and decrease of muscle tone. These effects last several hours and are in contrast to the hypernoea and behavioural activation which occurs during hypoxia soon after birth and in the adult. Transection and lesion studies in fetal sheep suggest that hypoxia activates a descending inhibition of respiratory and other motor activities which either originates in the pons or is conveyed to medullary and spinal levels of the neuraxis by fibres through the pons in the region of the Kolliker‐Fuse nucleus. Recently, using FOS immunohistochemistry we have identified cells in the medial parabrachial complex which are activated by hypoxia in fetal sheep, but not newborn lambs. It is proposed that these cells have descending inhibitory connections with respiratory and spinal motor pathways, but the precise anatomy and neuro‐chemistry of such pathways is unknown. It is not known if the parabrachial cells are directly sensitive to low P o2 or receive input from other centres or peripheral receptors which monitor arterial P o2 in the foetus. Nor is it known why these cells are not activated by low P o2 after birth.
REGULATION OF NEURAL PRECURSOR DIFFERENTIATION IN THE EMBRYONIC AND ADULT FOREBRAIN
Authors: Bartlett P. F. , Richards L. R. , Kilpatrick T. J. , Talman P. S. , Bailey K. A. , Brooker G. J. F. , Dutton R. , Koblar S. , Nurcombe V. , Ford M. , Cheema S. S. , Likiardopoulos V. , Murphy M. 
Published: June 2007

SUMMARY1. Precursors form the neuroepithelium of the developing cortex and also from the adult sub‐ventricular zone, can be cloned in vitro after stimulation with fibroblast growth factor (FGF)‐2 and have the potential to give rise to both neurons and glia. The generation of neurons from these clones can be stimulated by either a factor derived from an astrocyte‐precursor line, Ast‐1, or FGF‐1.2. Neuronal differentiation stimulated by FGF‐1 can be inhibited by diacylglycerol‐lipase inhibitor and mimicked by arachidonic acid, suggesting that the neuronal differentiation is signalled through the PCLγ pathway.3. The sequential expression of FGF‐2 and FGF‐1 within the developing forebrain neuroepithelium fits with the different functions the two FGF play in precursor regulation.4. We have shown that the precursor response to FGF‐1 is regulated by a heparan sulphate proteoglycan (HSPG) expressed within the developing neuroepithelium. Precursors restricted to the astrocyte cell lineage can be stimulated by epidermal growth factor or FGF‐2; however, the differentiation into GFAP positive astrocytes appears to require a cytokine acting through the leukaemia inhibitory factor β receptor.
DEVELOPMENTAL SIGNALLING
Authors: Hendry I. A. , Johanson S. O. , Heydon K. 
Published: June 2007

SUMMARY1. In investigating the communication paths between target tissue and neurons we have been led to propose two classes of neurotrophic factors. One comprises the factors which transport themselves, the other factors relying on the transport of a second messenger. The former may have labile second messenger systems necessitating the translocation of agonist and receptor from the nerve terminal to the cell body and the latter must possess a stable second messenger system that itself is sufficiently robust to survive the transport to the cell body.2. One such class of stable messengers may be the GTP‐binding protein family and it has been shown that the alpha subunits of both Giα and Gzα can be retrogradely transported in the mouse sciatic nerve.3. Examination of the cell bodies in the dorsal root ganglia revealed that Gα accumulated in the nucleus of cells with intact axons but that 24 h after axonal ligation this immunoreactivity decreased.4. It is suggested that Gzα is activated at the nerve terminal and it, or at least its alpha subunit, undergoes retrograde transport to the cell body where it accumulates in the nucleus.
SCHWANN CELLS AND THE REGROWTH OF AXONS IN THE MAMMALIAN CNS: A REVIEW OF TRANSPLANTATION STUDIES IN THE RAT VISUAL SYSTEM
Authors: Harvey A. R. , Plant G. W. , Tan M. M. L. 
Published: June 2007

SUMMARY1. We have used peripheral nerve transplants or cultured Schwann cells grafted in association with different types of polymer to study axonal regrowth in the rat visual system. In some instances the glia were co‐grafted with fetal tectal tissue.2. The studies have two main aims: (i) to determine whether retinal axons can be induced to regrow at a site distant from their cell soma, that is, after damage to the brachial region of the optic tract; (ii) to determine whether retinal axons exposed to Schwann cells retain the ability to recognize their appropriate target neurons in CNS tissue.3. In brachial lesion studies, Schwann cells were placed in the lesion site in association with nitrocellulose papers, within polycarbonate tubes in the presence or absence of a supporting extracellular matrix (ECM), or within polymer hydrogel scaffolds. Autologous sciatic nerve grafts were also used. Immuno‐histochemical studies revealed the presence of regenerating axons within all polymer bridges. Regrowth of retinal axons was also seen, however, growth was not extensive and was limited to the proximal 1–1.5 mm of the implants.4. In target innervation experiments, two surgical paradigms were developed. In one experiment, a segment of sciatic nerve was autografted onto the transected optic nerve in adult rats and the distal end of each graft was placed adjacent to fetal tectal (target) tissue implanted into the frontal cortex. To date, we have not been able to demonstrate selective recognition of target regions within tectal transplants by retinal axons exiting the sciatic nerve implants.5. In the second experiment, Schwann cells were mixed with fetal tectal cells and co‐grafted to the midbrain of newborn host rats. Schwann cells altered the characteristic pattern of host retinal growth into tectal grafts; in some cases axons were induced to grow away from appropriate target areas by nearby co‐grafted Schwann cells.6. In summary, Schwann cell/polymer scaffolds may provide a useful way of promoting the regrowth of damaged axons in the CNS, however: (i) in adults, at least, their effectiveness is reduced if they are located at a distance from the cell bodies giving rise to regenerating axons; (ii) in some circumstances exposure to a peripheral glial environment may affect the capacity of regenerating axons to recognize appropriate target cells in the CNS neuropil.
EFFECTS OF SODIUM DEPLETION ON TISSUE CONCENTRATIONS OF THE NATRIURETIC HORMONE VASOACTIVE INTESTINAL PEPTIDE
Authors: Duggan K. A. , Ye V. Z. C. 
Published: June 2007

SUMMARY1. Variations in dietary sodium intake have been shown to affect the plasma concentration, the metabolic clearance rate and secretion rate of vasoactive intestinal peptide (VIP). In this study we sought to determine the effect of sodium depletion on the concentration of VIP in plasma and in three tissues, namely heart, lung and kidney.2. Male Sprague‐Dawley rats were placed on low or normal sodium diets and drinking water ad libitum. A third group was placed on a low salt diet and in addition were given frusemide, 1 mg/kg per day in the drinking water. After 7 days the rats were killed, a blood sample collected and tissues harvested. VIP concentrations were determined by radio‐immunoassay on unextracted plasma and in tissue after extraction.3. There were significant differences between the three groups in the Concentration of VIP in the lung (P< 0.0005), kidney (P< 0.005) and plasma (P< 0.025) but not the heart. In the group that received frusemide and the low sodium diet, VIP in the lung was significantly lower than the low sodium (P< 0.005) and normal sodium (P< 0.0001) groups. Similar differences were noted in the kidney (frusemide vs low sodium, P< 0.001; frusemide vs normal, P< 0.01) and plasma (frusemide vs low sodium P< 0.001, frusemide vs normal P< 0.05).4. We conclude that sodium depletion decreases the concentration of VIP in plasma and in its metabolizing tissues.
EFFECTS OF CAPTOPRIL ON [3H]‐NOREPINEPHRINE RELEASE IN RAT CENTRAL NERVOUS SYSTEM
Authors: Tsuda Kazushi , Tsuda Seiko , Nishio Ichiro , † Yoshiaki Masuyama , Goldstein Menek 
Published: June 2007

SUMMARY1. The present study was performed to investigate the effects of captopril (an angiotensin converting enzyme inhibitor, ACE‐I) on noradrenergic transmission in the rat central nervous system.2. Slices of rat hypothalamus and medulla oblongata were prepared and prelabelled with [3H]‐norepinephrine. Slices were continuously superfused with Krebs‐Ringer solution, and electrical stimulation (1 Hz) was performed.3. Captopril significantly inhibited the stimulation‐evoked [3H]‐norepinephrine release from rat hypothalamic slices in a dose‐dependent manner (S2/S1 ratio: control 0.904 ± 0.025, n= 6, captopril l × 10‐5 mol/L 0.617 ± 0.043, n= 6,P<0.05, captopril 5 ×10‐5 mol/L 0.547±0.037, n= 6, P<0.05). However, the basal release of [3H]‐norepinephrine was not affected by captopril.4. Captopril also reduced the stimulation‐evoked [3H]‐nor‐epinephrine release in the medulla oblongata (S2/S1 ratio: control 0.878 ± 0.018, n= 6, captopril 3.3 × 10‐5 mol/L 0.624 ± 0.046, n= 6, P<0.05).5. These results show that captopril might inhibit the stimulation‐evoked norepinephrine release in rat hypothalamus and medulla oblongata. Although the precise mechanisms underlying the neurosuppressive effect of captopril are still uncertain, the finding suggests that the inhibition of noradrenergic transmission might be related to the central action of the ACE‐I.
COMPARISON OF RESPONSES TO AMINOGUANIDINE AND Nω‐NITRO‐L‐ARGININE METHYL ESTER IN THE RAT AORTA
Authors: Yen Mao‐Hsiung , Chen Shiu‐Jen , Wu Chin‐Chen 
Published: June 2007

SUMMARY1. We have compared the effect of aminoguanidine with that of Nω‐nitro‐L‐arginine methyl ester on isolated thoracic aortic rings obtained either from endotoxin (lipopolysaccharide, 10 mg/kg, i.v. for 3 h) or vehicle (saline) treated rats.2. Administration of endotoxin for 3h resulted in a hypo tension and a significant reduction of pressor responses to nor‐epinephrine (1 μg/kg, i.v.) in the anaesthetized rat.3. In intact rings obtained from vehicle treated rats, amino guanidine (0.3 and 1mmol/L) had no significant effect on acetylcholine‐induced relaxation (10‐9–10‐5mol/L), whereas Nω‐nitro‐L‐arginine methyl ester (0.3mmol/L and 1mmol/L) abolished that response, suggesting that aminoguanidine does not inhibit the activity of constitutive nitric oxide synthase.4. Relaxation induced by L‐arginine (10‐6–10‐2mol/L) was competitively inhibited by both aminoguanidine (0.3 mmol/L) and Nω‐nitro‐L‐arginine methyl ester (0.3 mmol/L) in endo thelium‐denuded aortic rings obtained from endotoxin treated rats.5. Three hours of endotoxaemia was associated with an impairment of contraction to norepinephrine (10‐9–10‐6 mol/L) in the endothelium‐denuded aorta ex vivo. This hyporeactivity to norepinephrine was partially restored by treatment of the vessels either with aminoguanidine (0.3 mmol/L) or with Nω‐nitro‐l‐arginine methyl ester (0.3 mmol/L) in vitro.6. These results in isolated thoracic aortae of the rat reinforce that aminoguanidine is a selective inhibitor of the inducible nitric oxide synthase, whereas Nω‐nitro‐L‐arginine methyl ester is a non‐selective inhibitor of both the inducible and constitutive nitric oxide synthase.
FUNCTIONAL AND STRUCTURAL CHARACTERISTICS OF EXPERIMENTAL FK 506 NEPHROTOXICITY
Authors: Andoh Takeshi F. , Burdmann Emmanuel A. , Lindsley Jessie , Houghton Donald C. , Bennett William M. 
Published: June 2007

SUMMARY1. FK 506 (Tacrolimus, Prograf®) is a novel Immunosuppressant which is effective in solid organ transplantation and autoimmune diseases. The lack of a suitable animal model has hindered the study of the nephrotoxicity of the drug which has emerged as a common adverse effect in clinical trials. We report both acute and chronic nephrotoxicity with tacrolimus (FK) in which renal structure and function are worsened by sodium depletion.2. Pair fed male Sprague‐Dawley rats were given FK (3 or 6 mg/kg, p.o.) or vehicle for 7, 21 and 42 days on low salt or normal diet. The FK whole blood trough levels achieved (3–10ng/mL) were similar to those observed in FK treated transplant patients.3. In salt depleted animals treated for 7 days, FK (6 mg/kg) decreased renal blood flow and glomerular filtration rate (1.8 ± 0.1 and 0.2 ± 0.1 mL/min per 100g vs 2.9 ± 0.2 and 1.1 ± 0.1 mL/min per 100 g in the vehicle group, P<0.01).4. After 21 days of treatment of FK on low salt diet but not normal salt, FK induced focal collapse and vacuolization in proximal tubules and discrete or confluent zones of tubulointerstitial oedema and mononuclear cell infiltration.5. After 42 days in salt depleted rats, there was significant tubulointerstitial scarring that was associated with an increased plasma renin activity (PRA) (64 ± 10 vs 30 ± 4 ng AI/mL per h in the vehicle group, P< 0.05). Animals given normal salt diets did not develop significant histological lesions even up to 42 days.6. Sodium depletion is critical for the development of FK induced progressive striped tubulointerstitial fibrosis associated with an increase in PRA. These data suggest a role for the renin‐angiotensin system in the pathogenesis of functional and structural changes of chronic FK nephrotoxicity.
OPIOID MECHANISMS CONTROLLING RENAL FUNCTION
Authors: Kapusta Daniel R. 
Published: June 2007

SUMMARY1. Over the past 50 years considerable evidence has been reported suggesting that endogenous opioids participate in the control of renal function.2. Exogenous administration of opioids produces profound changes in the renal excretion of water and sodium.3. Opioids produce changes in urine output and urine sodium excretion by multiple integrated neural and hormonal mechanisms within the periphery, central nervous system and kidneys.4. Although opioid antagonist administration does not consistently reveal an action of endogenous opioid systems on renal function, this may result from the quiescent nature of the endogenous opioid system under basal conditions.5. Manipulations that activate endogenous opioid systems have begun to reveal important, previously unrecognized mechanisms that control kidney function and can enhance renal tubular sodium reabsorption in normal and potentially pathological states.
ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS AND KININ METABOLISM: EVIDENCE THAT ACE INHIBITORS MAY INHIBIT A KININASE OTHER THAN ACE
Authors: Campbell Duncan J. 
Published: June 2007

SUMMARY1. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, and also metabolizes bradykinin‐(1–9) to bradykinin‐(1–7) and bradykinin‐(1–7) to bradykinin‐(1–5). Increases in endogenous kinin levels may contribute to the therapeutic effects of ACE inhibitors.2. ACE inhibitors increase vascular levels of both bradykinin‐(1–9) and its ACE cleavage product bradykinin‐(1–7), at doses below the threshold for ACE inhibition, leading to the proposal that ACE inhibitors may also inhibit a non‐ACE kininase which cleaves both kinin peptides; this non‐ACE kininase may be the major pathway of kinin metabolism in the vasculature and some other tissues.3. In support of this proposal, ACE inhibitors potentiate bradykinin‐(1–9) effects at doses which have little or no effect on ACE activity, as indicated by angiotensin I conversion to angiotensin II. ACE inhibitors also potentiate the actions of ACE‐resistant kinin analogues, which may be susceptible to metabolism by a non‐ACE kininase.4. Identification and characterization of the putative non‐ACE kininase which is inhibited by ACE inhibitors may reveal novel approaches to the tissue‐specific modulation of kinin levels.
LONG‐TERM OUABAIN ADMINISTRATION DOES NOT ALTER BLOOD PRESSURE IN CONSCIOUS SPRAGUE‐DAWLEY RATS
Authors: Li Ming , Martin Allison , Wen Cheng , Turner Steven W. , Lewis Lynley K. , Whitworth Judith A. 
Published: June 2007

SUMMARY1. We tested the ability of ouabain to cause chronic hyper tension by continuously infusing ouabain for 28 days (mini‐osmotic pump implantation; i.p.). The blood pressure and metabolic effects of sham (150 mmol/L NaCI; n= 12) or ouabain infusion (10 μg/kg per day; n= 14; 100 μg/kg per day; n = 14) were examined in conscious Sprague‐Dawley rats.2. Plasma ouabain concentrations measured after 28 days of ouabain infusion were as follows: sham, not detectable (n= 11); ouabain 10 μg/kg per day, 0.60 ± 0.07 nmol/L (n= 14); and ouabain 100 μg/kg per day, 7.17 ± 0.57 nmol/L (n= 14; P < 0.001).3. Sham or ouabain infusion did not alter food intake, bodyweight, water intake or urine output in conscious rats.4. Blood pressure was not altered by sham treatment. Ouabain at 10 μg/kg per day or 100 μg/kg per day did not produce consistent rises in blood pressure. Ouabain at 10 μg/kg per day increased blood pressure on treatment day 12 only (+ 6mmHg; P < 0.05), while at 100μg/kg per day blood pres sure increased on treatment days 16 (+ 9 mmHg; P < 0.05) and day 18 (+ 8mmHg; P < 0.05) only. There was no significant difference in blood pressure between sham and ouabain groups.5. Renal blood flow was decreased in rats infused with ouabain at 10 μg/kg per day (2.0 ± 0.3 mL/min per 100 g body‐weight; n= 5; P < 0.01) and 100 μg/kg per day (2.2 ± 0.4 mL/ min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (3.5 ± 0.2 mL/min per 100 g bodyweight; n= 6). Renal vascular resistance was increased in rats treated with ouabain at 10 μg/kg per day (65.5 ± 12.6 mmHg/mL per min per 100 g bodyweight; n= 5; P < 0.01) and 100 μg/kg per day (66.0 ± 15.6 mmHg/mL per min per 100 g bodyweight; n= 7; P < 0.05) compared with sham treatment (32.6 ± 2.5 mmHg/mL per min per 100 g bodyweight; n= 6).6. High plasma concentrations of ouabain do not cause consistent increases in blood pressure in conscious Sprague‐Dawley rats.
TRANSCRIPTIONAL CONTROL AND THE REGULATION OF ENDOCRINE GENES
Authors: Zajac J. D. , Chilco P. J. 
Published: June 2007

SUMMARY1. Endocrine genes are regulated at a number of levels during their expression. Regulation can occur during transcription, mRNA splicing, mRNA degradation, translation, or post‐translational processing of protein precursors.2. Transcription is controlled by an increasingly well studied and enlarging family of transcription factors that bind to basal control DNA sequences (promoters) and transcriptional activator sequences (enhancers).3. Steroid receptors act as transcription factors, as do the proteins involved in the gene regulation by cyclic AMP. Parathyroid hormone related protein is typical of many endocrine genes in that it is regulated by multiple agonists including glucocorticoids and hormones activating the cyclic AMP cascade.
MICROCOMPUTER STATISTICS PACKAGES FOR BIOMEDICAL SCIENTISTS
Authors: Ludbrook John 
Published: June 2007

SUMMARY1. There are hundreds of commercially available microcomputer statistics packages, ranging from the very cheap and elementary to the very expensive and complex, and from the very general to the very specialized. This review covers only those that appear to be popular with biomedical investigators who deal with fairly small sets of data but may wish to use relatively complex analytical techniques.2. It is highly desirable, if not essential, that biomedical investigators who use microcomputer statistics packages have access to a spreadsheet program. These provide sample statistics and simple statistical analyses but, more importantly, they are often the best way of entering data into the files of the statistics packages proper.3. A vital component of any statistics package is its manual. This should be easy to follow, but at the same time it must provide full documentation of, and references to, precisely how the various statistical tests are performed.4. Some packages are elementary and offer only a narrow range of test procedures (mini‐packages). Some are designed to be used as statistical libraries and programming tools for professional statisticians. Between these extremes are the general purpose packages (mid‐range, maxi‐ and supermaxi packages) that constitute the main body of this review.5. All the packages reviewed have some shortcomings or flaws. It is argued that the ideal package for biomedical investigators should have the following features: (i) it should provide a wide range of test procedures for analysing continuous, rank‐ordered, and categorical data; (ii) the way in which these tests are carried out should be clearly stated in the manual; and (iii) lastly, although not unimportantly, the package should be easy to use.6. It is recommended that biomedical investigators purchase a package that provides many more statistical routines than they use in their everyday practice. Provided the manual is a good one and the package itself has no serious flaws, this is an excellent stimulus to continuing education in statistical techniques.
NAFAMOSTAT ENHANCES IBMX AND SECRETIN‐STIMULATED WATER AND BICARBONATE SECRETION IN THE ISOLATED, BLOOD‐PERFUSED DOG PANCREAS
Authors: Horiuchi A. , Iwatsuki K. , Chiba S. 
Published: June 2007

SUMMARY1. The effect of nafamostat mesilate, a synthetic protease inhibitor, on pancreatic exocrine secretion was investigated in isolated, blood‐perfused dog pancreas.2. Intra‐arterial injections of nafamostat (2–10 gmol) dosedependently enhanced water and bicarbonate secretion stimulated by 3‐isobutyl‐1‐methylxanthine (IBMX) or secretin, although nafamostat alone did not affect the basal secretion.3. In the nafamostat‐enhanced pancreatic juice, bicarbonate concentrations were increased dose‐dependently as compared with the control, while protein concentrations were not significantly changed.4. These results indicate that nafamostat enhances IBMX and secretin‐stimulated water and bicarbonate secretion, which may be mediated through CAMP activation.