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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 415 records · Page 23Linked to original sources
PubMed1989

Quantitative analysis of peptide levels and neurogenic extravasation following regeneration of afferents to appropriate and inappropriate targets.

We have studied quantitatively the levels of substance P and calcitonin gene-related peptide in nerves innervating skin and muscle of rats, and examined the effects of cross-anastomosing these nerves so that they regenerate to an inappropriate target. We have also compared the ability of nerves to induce neurogenic extravasation with their peptide content. Peptide was measured by radioimmunoassay in the proximal section of ligated peripheral nerves, and neurogenic oedema was measured by determination of Evans Blue extravasation induced by either systemic capsaicin treatment or topical mustard oil application. The levels of these peptides are higher in cutaneous nerves than muscle nerves. This cannot be explained by differences in the number of fibres in the nerves studied. The levels of peptides fall when cutaneous afferents reinnervate muscle, and rise when muscle afferents reinnervate skin. We suggest that these changes occur because of some tissue-specific trophic influence arising from the tissue innervated. The ability to produce extravasation in skin is highly correlated with the substance P and calcitonin gene-related peptide levels of its innervation, even when this occurs in inappropriate nerves which do not normally produce extravasation.

Anastomosis, Surgical↗
PubMed1989

Regional distribution of chromogranin B 420-493-like immunoreactivity in the pituitary gland and central nervous system of man, guinea-pig and rat.

The distribution of chromogranin B 420-493-like immunoreactivity was investigated in the pituitary gland and central nervous system of man, guinea-pig and rat, by using two different antibodies. In man, highest chromogranin B 420-493-like immunoreactivity concentrations were found in the pituitary gland, chromogranin B 420-493 (1-17)-like immunoreactivity 74.3 +/- 8.5 (mean +/- S.E.M. pmol/g wet wt tissue) and chromogranin B 420-493 (20-38)-like immunoreactivity 2017.0 +/- 142.3, followed by the hypothalamus and substantia nigra. In the spinal cord, the highest concentration was found in the sacral dorsal area. Chromogranin B 420-493-like immunoreactivity was detected in human cerebrospinal fluid, chromogranin B 420-493 (1-17)-like immunoreactivity 376.7 +/- 77.9 and chromogranin B 420-493 (20-38)-like immunoreactivity 1174.7 +/- 259.3 pmol/l cerebrospinal fluid. Chromogranin B 420-493-like immunoreactivity was also found in high concentrations in the guinea-pig and rat pituitary glands, but very low chromogranin B 420-493-like immunoreactivity levels were present in different parts of the brain of both species. Gel permeation chromatography and fast protein liquid chromatography analysis of eight different regions of human CNS showed multiple chromogranin B 420-493-like immunoreactivity peaks. The profile of pituitary extracts was different from those of other parts of the CNS and the cerebrospinal fluid. The profiles of guinea-pig and rat pituitary on gel chromatography and fast protein liquid chromatography were different again from those of human CNS. Examination of subcellular fractionation of whole rat brain showed highest concentrations of chromogranin B 420-493-like immunoreactivity in the synaptosome fractions. Chromogranin B 420-493-like immunoreactivity release was stimulated from rat pituitary cells by high potassium ion concentrations. These findings show that (1) chromogranin B 420-493-like immunoreactivity is widely distributed throughout the pituitary gland and CNS of three mammalian species, with the highest concentration in the pituitary gland, and it is also present in human cerebrospinal fluid, and (2) the processing of chromogranin B in the pituitary gland may be different from that in the other area of the CNS, so that it is possible chromogranin B or its fragments may play a neuroeffector role in the mammalian CNS.

Adult↗
PubMed1989

Atrial natriuretic peptide levels in plasma and in cardiac tissues after chronic hypoxia in rats.

1. Atrial natriuretic peptide (ANP) levels were measured in cardiac tissues and in plasma from adult rats exposed to chronic alveolar hypoxia for periods of 2 h, 24 h and 7 days. Levels were also measured in rats that were maintained in hypoxia for 7 days and then returned to air for 24 h. 2. Plasma ANP was not altered at 2 h but was significantly increased at both 24 h and at 7 days. Plasma ANP in animals exposed to hypoxia for 7 days was normal 24 h after returning to air breathing, despite the persistence of indices of pulmonary hypertension. 3. No significant right atrial hypertrophy was observed under these conditions of chronic hypoxia. A reduction in right atrial ANP content was found at 24 h and was accompanied by a decrease in the number of electrondense granules per right atrial muscle cell. After exposure to hypoxia for 7 days, right atrial ANP and granule number was not different from control, and no alteration was found in right atrial ANP level after removal from the hypoxic environment. 4. No significant right ventricular hypertrophy was produced by exposure to hypoxia for 2 or 24 h. In the former group ventricular ANP had decreased significantly compared with control. Right ventricular hypertrophy was found in both the hypoxic groups after exposure for 7 days, when selective increases in right ventricular ANP content were found. 5. These findings are consistent with the hypothesis that ANP release occurs on exposure to chronic hypoxia and is independent of the associated cardiac hypertrophy and pulmonary vascular remodelling. The findings may have relevance to the natriuresis and reported changes in the renin-angiotensin-aldosterone axis under hypoxic conditions.

Animals↗
PubMed1989

Atrial natriuretic peptide: physiological release associated with natriuresis during negative pressure breathing in man.

1. Negative pressure breathing was one of the first physiological tools used to study the renal effects of redistribution of the blood volume from the peripheries to the thorax. The recent discovery of a putative natriuretic hormone (atrial natriuretic peptide, ANP) in cardiac atrial tissue has rekindled interest in the effect of the cardiovascular system on renal function. We have therefore studied the effects of this physiological manoeuvre on plasma ANP concentrations and renal responses. 2. Plasma concentrations of ANP, plasma renin activity and plasma aldosterone concentration were measured during an 80 min period of negative pressure breathing at -12 cmH2O pressure in six hydrated normal subjects. Identical control studies were performed in the same subjects at at least 1 week apart. 3. Negative pressure breathing resulted in a natriuresis and diuresis which were associated with a significant rise in plasma ANP concentration. The natriuresis occurred despite an increase in plasma renin activity and in plasma aldosterone concentration. 4. These findings, under specific carefully controlled conditions, support the previously contentious postulate that negative pressure breathing enhances sodium excretion, in addition to its well-recognized diuretic effect. They add further weight to the hypothesis that expansion of the central blood volume is an important stimulus to the release of ANP from the heart (acting by way of atrial distension), and suggest that changes of plasma ANP concentration may have induced the natriuresis which occurred in the face of a modest activation of the sodium-retaining renin-aldosterone system.

Adult↗
PubMed1989

Differential blood pressure and hormonal effects after glucose and xylose ingestion in chronic autonomic failure.

1. To investigate whether carbohydrate contributes to postprandial hypotension in autonomic failure, the cardiovascular, biochemical and hormonal effects of oral glucose and an iso-osmotic solution of oral xylose were studied on separate occasions in six patients with chronic autonomic failure. The effects of oral glucose were also studied in eight normal subjects. 2. In the patients oral glucose lowered blood pressure substantially (-34 +/- 7% at 60 min, area under curve -24.9 +/- 3.5%, P less than 0.001) and for a prolonged period (-25 +/- 4% at 120 min). Plasma noradrenaline levels did not change. In the normal subjects blood pressure was unchanged and plasma noradrenaline rose, suggesting a compensatory increase in sympathetic nervous activity. 3. In the patients xylose caused a smaller and more transient fall in blood pressure (-15 +/- 6% at 90 min, area under curve -8.9 +/- 4%, P less than 0.05) with a non-significant elevation in packed cell volume (36.7 +/- 1.8 to 38.2 +/- 1.8). It was therefore unclear if xylose was exerting osmotic effects within the bowel which contributed to the small blood pressure fall. Packed cell volume did not change in either the patients or normal subjects after glucose. 4. In the patients and normal subjects plasma insulin rose after glucose. Insulin levels were unchanged after xylose. Levels of pancreatic polypeptide and neurotensin, a potential vasodilator, rose in the patients only. The latter rose to a similar extent after both glucose and xylose, making it unlikely that neurotensin alone accounted for the hypotension. 5. These studies indicate that the carbohydrate components of a meal, and in particular those causing insulin release, contribute to postprandial hypotension in patients with autonomic failure.

Administration, Oral↗
PubMed1989

Prevention of glucose-induced hypotension by the somatostatin analogue octreotide (SMS 201-995) in chronic autonomic failure: haemodynamic and hormonal changes.

1. The haemodynamic and hormonal changes following glucose ingestion (1 g/kg) were determined before and after pretreatment with either placebo or the somatostatin analogue, octreotide (SMS 201-995, 50 micrograms subcutaneously), in seven patients with chronic autonomic failure. 2. In the placebo phase, after glucose, there was a marked and prolonged fall in blood pressure with no change in cardiac index and peripheral blood flow. Plasma insulin and neurotensin levels increased, whereas glucagon, vasoactive intestinal polypeptide, noradrenaline and adrenaline levels were unchanged. 3. Octreotide transiently raised blood pressure and prevented glucose-induced hypotension. There were no changes in cardiac index or peripheral blood flow. Plasma insulin and neurotensin levels did not rise. Plasma glucose levels increased more slowly but reached a similar level to the placebo phase. 4. We conclude that in autonomic failure patients, glucose-induced hypotension was not accompanied by changes in cardiac index or peripheral blood flow, indicating a lack of compensation to probable splanchnic vasodilatation. The hypotension was prevented by the peptide release inhibitor, octreotide, with no change in cardiac index or in peripheral blood flow, suggesting an effect on the splanchnic vasculature, probably through inhibiting release of vasodilatatory pancreatic and gut peptides.

Adult↗
PubMed1989

Role of neuromedin B in the control of the release of thyrotropin in the rat.

Neuromedin B (NB), a bombesin-like peptide, was first isolated from porcine spinal cord and subsequently found in the central nervous systems of rat, cat, and human. Immunocytochemical studies have shown that NB is present in hypothalamus and various other regions of the brain and in thyrotrophs of the anterior pituitary of the rat. The possible physiological role of NB in the hypothalamic-pituitary axis is not known. Therefore, we studied the in vivo effect of this peptide on the plasma levels of thyrotropin (TSH) after administering NB to conscious freely moving adult male rats. When injected i.v., only the highest dose of NB (50 micrograms, 44.2 nmol) significantly lowered plasma TSH levels relative to levels in saline controls. When injected intraventricularly, NB doses of 0.5 and 5 micrograms (0.44 and 4.42 nmol, respectively) lowered plasma TSH levels with a 15-min latency period. Responsiveness of the pituitary to TSH-releasing hormone (TRH) was tested after the effective dose of NB was administered i.v. The increase in plasma TSH levels after the i.v. injection of 1 microgram of TRH was not altered by NB. NB at 10(-9) to 10(-7) M also reduced TSH release from hemipituitaries incubated in vitro without decreasing the response to TRH. Consequently, NB appears to have a direct inhibitory effect on TSH release from thyrotrophs. Since the response to TRH was not depressed, NB appears to act on a separate NB thyrotroph receptor that suppresses TSH release by a TRH-independent mechanism. After antiserum directed against NB was injected into the third ventricle, there was a highly significant elevation of the plasma level of TSH, beginning at 4 hr and increasing at 6 hr, relative to initial levels and levels in normal rabbit serum-injected controls. These results indicate that NB has a tonic suppressive effect on TSH release and is a physiologically significant TSH-release-inhibitory factor.

Animals↗
PubMed1989

Endothelin 1, an endothelium-derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia.

The localization of endothelin 1 mRNA and endothelin-like immunoreactivity was investigated in samples of neurologically normal nervous system tissue from 10 adults by using in situ hybridization and immunocytochemistry. Tissue sections of spinal cord and dorsal root ganglia were hybridized with an 35S-radiolabeled endothelin 1 complementary RNA probe. Autoradiograms showed labeled neurons in the spinal cord (laminae IV-VI and many motoneurons) and numerous small and large neurons in the dorsal root ganglia. Endothelin 1 transcripts were also found in association with the endothelial layer of some blood vessels in the white matter of the spinal cord. A similar distribution of immunoreactivity was seen using three antisera to endothelin 1, but fewer cells were immunostained than were labeled after the hybridization. Two other endothelin 1 antisera immunostained the endothelial lining of blood vessels in the spinal cord white matter but not neurons. In the ganglia, endothelin 1 transcripts were localized to all cells expressing beta-preprotachykinin and most expressing calcitonin gene-related peptide mRNAs; in the majority of the motoneurons, coexistence of endothelin 1 and calcitonin gene-related peptide mRNAs was noted. There was a similar pattern of coexistence for respective peptide immunoreactivities in the ganglia and spinal cord. The expression of endothelin 1 mRNA in distinct neuronal cell types suggests that this peptide plays a part in neural transmission/modulation and adds a further dimension to the known vascular-related actions of endothelin 1.

Endothelins↗
PubMed1989

Hormonal and metabolic responses to cholecystectomy: comparison of extradural somatostatin and diamorphine.

We have studied the metabolic and hormonal responses to surgery, and the pain scores and analgesic requirements in 24 patients undergoing cholecystectomy, allocated randomly to three groups to receive either general anaesthesia alone, or general anaesthesia with extradural diamorphine 0.1 mg kg-1, or general anaesthesia with extradural somatostatin to a total dose of somatostatin 3 mg. The only significant effect of extradural diamorphine was a decrease in the glucose response to surgery. Somatostatin 3 mg by the extradural route caused a significant increase in the concentration of circulating somatostatin which resulted in a significant decrease in plasma growth hormone and insulin after 60 min of surgery, together with an increase in plasma glycerol concentration. Patients in the diamorphine group required significantly less i.v. analgesia in the postoperative period than the other two groups. Intraoperative somatostatin failed to provide any postoperative analgesia.

Adult↗
PubMed1989

Autoradiographic localization of endothelin-1 binding sites in the cardiovascular and respiratory systems.

Specific high-affinity binding sites for endothelin-1 (ET-1) have been demonstrated in peripheral tissues using the technique of in vitro receptor autoradiography. Binding was time dependent and saturable and inhibited by coincubation with an excess of unlabeled ET-1 but resistant to dissociation. Binding sites were localized to blood vessels of all sizes including coronary arteries, intrapulmonary vessels, and intrarenal and intrasplenic arteries. In addition, high-affinity binding sites were identified on airway smooth muscle, over alveolar septa, and on nerve trunks. Scatchard analysis of the data revealed a Bmax of 250 amol/mm2 and a Kd of 0.1 nM for the binding of rat tracheal smooth muscle, with similar values for porcine coronary artery. The localization of binding sites is consistent with the known effects of ET-1 and suggests a direct action on specific receptors.

Animals↗
PubMed1989

Studies with endothelin-3 and endothelin-1 on rat blood pressure and isolated tissues: evidence for multiple endothelin receptor subtypes.

In an anesthetized rat, endothelin-1 (ET-1) causes a rapid, transient fall in blood pressure followed by a large, sustained rise. Rat endothelin-3 (ET-3) differs from porcine endothelin-1 (ET-1) by six amino acids and is 20 times less potent at contracting rat aortic strips. The comparative effects of ET-3 and ET-1 on blood pressure were studied in anesthetized rats in which the arterial blood pressure was continually monitored. Dose-response curves for the contraction of rat stomach strips, guinea pig ileum, and guinea pig trachea were also constructed. In the anesthetized rat, ET-3 was slightly (but not significantly) less potent than ET-1 at producing the transient blood pressure fall but was three times less potent at causing the subsequent rise. The two peptides were equipotent at contracting rat stomach strips but ET-3 was 10 times less potent at contracting the guinea pig ileum. Rat ET-3 was less potent at contracting the guinea pig trachea and had a lower maximal effect. These results suggest the existence of multiple receptor subtypes for ET.

Animals↗
PubMed1989

Plasma atrial natriuretic factor and graft function in renal transplant recipients.

In order to determine the relationships between allograft function and the recipient's plasma concentrations of atrial natriuretic factor (ANF), plasma ANF was measured by radioimmunoassay for 14 days after cadaveric renal transplantation in 9 patients aged 19-64 years. All received immunosuppression with prednisolone, azathioprine, and cyclosporine. No patient was in heart failure. During the study period, six grafts functioned, and three were nonfunctioning--two due to rejection and one to acute tubular necrosis. Plasma ANF concentration at the time of transplantation was 48 +/- 16 pmol/L (mean +/- SEM) range 15-145 pmol/L. In the six patients with functioning grafts, ANF declined in parallel with the fall in serum creatinine (658 +/- 35 to 210 +/- 34 mumol/L). In the three with nonfunctioning grafts, serum creatinine and plasma ANF concentration both increased. There was overall a significant linear relation between serum creatinine and plasma ANF (r = 0.527, P less than 0.001). The changes in plasma ANF after renal transplantation bore no relationship to changes in body weight or blood pressure. However, plasma ANF concentration was related to allograft fractional sodium excretion (r = 0.687, p less than 0.001). We conclude that elevated plasma ANF concentrations in end-stage renal disease are restored to normal by successful renal transplantation, implying that renal function is a determinant of plasma ANF concentration. Circulating plasma ANF may also have a direct effect on allograft sodium excretion.

Adult↗
PubMed1989

Galanin: hydrokinetic action on salivary glands in man.

Galanin was infused intravenously into eight healthy volunteers at a dose of 40 pmol kg-1 min-1 for 1 h to investigate the pharmacological effects of this peptide on the postprandial sialagogical response in man. Galanin significantly increased the salivary volume and the saliva output of sodium, chloride and bicarbonate compared to control saline infusion, but had no effect on the output of potassium and alpha-amylase. An increase in salivary pH was also observed. The increase in salivary volume may indicate a physiological role of galanin in the control of salivary secretion.

Adult↗
PubMed1989

Resistance of metastatic pancreatic endocrine tumours after long-term treatment with the somatostatin analogue octreotide (SMS 201-995).

Ten patients with metastatic pancreatic endocrine tumours were treated with the long-acting somatostatin analogue octreotide (SMS 201-995). Three patients showed no response, clinically or biochemically, and treatment was therefore withdrawn. The seven remaining patients continued treatment for a median period of 28 months (range 13-54 months). Treatment was initially effective, symptoms improved and the concentrations of tumour-related hormones were reduced. Worsening of symptoms and rising levels of tumour-related hormone concentrations occurred a median of 5 months (range 1-6 months) after the start of therapy and were initially reversed by increasing the dose of octreotide over a median of 10 months (range 6-16 months). However, after a median of 13 months (range 5-34 months) at the maximum dosage, symptoms recurred and were no longer responsive to a further increase in dosage of octreotide or other therapeutic measures. All patients died within a period of 5 months once this resistant phase of their illness had been reached.

Adenoma, Islet Cell↗
PubMed1989

Hormonal response to blood volume expansion in diabetic subjects with and without autonomic neuropathy.

The hormonal and renal response to volume expansion, produced by water immersion for 4 h, was studied in 14 insulin-dependent diabetic subjects (seven without complications, seven with autonomic neuropathy) and in 14 age-and-sex-matched normal control subjects. The diabetic subjects showed an impaired natriuretic response to volume expansion (total amount of sodium excreted 21 mmol compared to 39 mmol in normals, P less than 0.01) but the response did not differ in those with and without autonomic neuropathy. There was no significant difference in the suppression of plasma renin or aldosterone during immersion in either group. Plasma catecholamines suppressed on immersion in all groups. Basal values were lowest in the group with autonomic involvement. Atrial natriuretic peptide levels showed a twofold rise (from 4.8 to 9.6 pmol/l, P less than 0.01) on immersion. There was no significant difference in the levels of this hormone between diabetic patients and normal subjects or between those diabetics with and those without autonomic neuropathy. The present study confirms that diabetic subjects retain sodium avidly during volume expansion. This enhancement cannot be ascribed to any measurable difference in the levels of circulating hormones known to be involved in natriuresis and is not influenced by the presence of autonomic neuropathy.

Adult↗
PubMed1989

Penile response to intracavernosal vasoactive intestinal polypeptide alone and in combination with other vasoactive agents.

Intracavernosally injected vasoactive intestinal polypeptide (VIP) (2 micrograms and 4 micrograms) resulted in penile tumescence even in men with predominantly organic impotence. Papaverine and phentolamine were successful in inducing erections in all subjects studied but the addition of VIP to this combination improved the erectile response further. A combination of papaverine and VIP produced penile rigidity similar to that with papaverine and phentolamine. While intracavernosal VIP alone produced disappointing penile responses, its combination with papaverine potentiated the response to this drug, probably by increasing venous outflow resistance.

Adult↗
PubMed1989

Effect of enprostil on glucose and lipid metabolism in type 2 diabetes.

Enprostil, a dehydro-prostaglandin E2 analogue, has been tested as treatment for peptic ulcer. Its effect on blood glucose and lipid metabolism in Type 2 diabetes was assessed in a randomized, double-blind trial. Fifteen patients on sulphonylurea therapy received, in addition, enprostil 35 micrograms or placebo thrice daily for two weeks, with a 2-week wash-out before crossover. Data from 12 patients were analysed. After a 530 Cal test breakfast at the end of active treatment, plasma glucose rose from a fasting concentration similar to that after the last placebo dose (10.5 +/- 0.8 (+/- SE) and 10.6 +/- 1.1 mmol l-1 respectively) to 1, 2 and 3 h concentrations which were 1.5 to 2.1 mmol l-1 lower than on placebo (2 h concentration 14.6 +/- 0.9 vs 16.4 +/- 1.3 mmol l-1, p less than 0.05). Serum fructosamine concentrations at the end of active treatment and placebo were 3.66 +/- 0.22 and 3.78 +/- 0.24 respectively (p = 0.051). No changes in fasting or post-prandial insulin concentrations were observed. After 2 weeks of enprostil, fasting serum triglyceride (1.76 +/- 0.18 mmol l-1) and total cholesterol (6.27 +/- 0.29 mmol l-1) concentrations were lower than after placebo (2.14 +/- 0.25 and 7.35 +/- 0.46 mmol l-1, p = 0.031 and p = 0.002, respectively), the latter effect being primarily due to reduced LDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗