Biomedical subjects

P S Oturai

Publications and source records attributed to P S Oturai.

8 recordsLinked to original sources

PubMed2006

Vasoactive intestinal polypeptide evokes only a minimal headache in healthy volunteers.

The role of the parasympathetic nervous system in the pathogenesis of migraine is disputed. The headache-eliciting effect of the parasympathetic neurotransmitter, vasoactive intestinal polypeptide (VIP), and its effect on cerebral arteries and brain haemodynamics has not been systematically studied in man. We hypothesized that infusion of VIP might induce headache in healthy subjects and cause changes in cerebral haemodynamics. VIP (8 pmol/kg per min) or placebo (0.9% saline) was infused for 25 min into 12 healthy young volunteers in a crossover, double-blind design. Headache was scored on a verbal rating scale from 0 to 10, regional cerebral blood flow (rCBF) was measured with single-photon emission computed tomography and (133)Xe inhalation and mean flow velocity in the middle cerebral artery (V(meanMCA)) was measured with transcranial Doppler ultrasonography. The headache was very mild with a maximum score of 2 and described as a pressing or throbbing sensation. Five participants developed headache during VIP and one during placebo. During the infusion, a significant drop in V(meanMCA) was seen for VIP compared with placebo (P < 0.001), but the effect quickly waned and no difference was found when comparing the time between 30 and 120 min. In addition, no significant difference in the diameter of the MCA could be found during the infusion. No significant differences in rCBF (P = 0.10) were found between VIP and placebo. A marked dilation of the superficial temporal artery was seen (P = 0.04) after VIP in the first 30 min but no difference was found when comparing the time between 30 and 120 min. We found no difference in mean arterial blood pressure between VIP and placebo days but the heart rate increased significantly on a VIP day compared with a placebo day (AUC(0-30 min), P < 0.001). Plasma VIP was significantly higher on a VIP day compared with placebo (AUC(0-80 min), P < 0.001). These results show that VIP causes a decrease in V(meanMCA) without affecting rCBF. In spite of a marked vasodilator effect in the extracranial vessels and increased plasma VIP, healthy subjects developed only a very mild headache.

Adult↗

PubMed2006

Evaluation of Tc-99m-tetrofosmin single-photon emission computed tomography for detection of chronic exertional compartment syndrome of the leg.

Chronic exertional compartment syndrome (CECS) of the leg is a common, painful condition related to exercise and associated with increased muscle compartment pressure (CP). Invasive methods are currently the method of choice for diagnosing the condition. We investigated the use of Tc-99m-tetrofosmin perfusion single-photon emission computed tomography (SPECT) as a diagnostic tool compared with the gold standard, muscle CP measurement. In 14 subjects perfusion SPECT and CP were measured before and immediately after exercise leading to pain in the lower legs. Six subjects had increased pressures indicating the presence of CECS. In three (50%) of these muscular hypoperfusion was observed by perfusion SPECT. In eight subjects with normal CPs SPECT suggested muscular hypoperfusion. Because of the low diagnostic rates, sensitivity 50% and specificity 63%, Tc-99m-tetrofosmin perfusion SPECT seems not to be a useful method for diagnosing CECS.

Adult↗

PubMed2000

Effects of advanced glycation end-product inhibition and cross-link breakage in diabetic rats.

The accelerated formation of advanced glycation end-products (AGEs) due to elevated glycemia has repeatedly been reported as a central pathogenic factor in the development of diabetic microvascular complications. The effects of a novel inhibitor of AGE formation, NNC39-0028 (2,3-diaminophenazine), and a breaker of already formed AGE cross-links, N-phenacylthiazolium bromide (PTB), were investigated in streptozotocin-diabetic female Wistar rats. Diabetes for 24 weeks resulted in decreased tail collagen pepsin solubility, reflecting the formation of AGE cross-linking. Collagen solubility was significantly ameliorated by treatment with NNC39-0028, whereas PTB had no effect. Increased urinary albumin excretion (UAE) in diabetic rats was observed in serial measurements throughout the study period, and was not reduced by any treatment. Vascular dysfunction in the eye, measured as increased clearance of 125I-albumin, was induced by diabetes. NNC39-0028 did not affect this abnormality. This study demonstrated a pharmacological inhibition of collagen solubility alterations in diabetic rats without affecting diabetes-induced pathophysiology such as the increase in UAE or albumin clearance. Treatment with PTB, a specific breaker of AGE cross-links, had no effects in this study.

Albuminuria↗

PubMed1997

Proteoglycan expression in the normal rat kidney.

Proteoglycans constitute a heterogenous group of complex macromolecules, consisting of a backbone core protein and a variable number of sulfated polysaccharide side chains covalently linked to the core. A dual function for these polyanionic glycosaminoglycans in kidney physiology has been proposed: to maintain a fixed negative charge in the glomerular filtration barrier, and to bind and sequester cytokines essential for renal development and function. With the aim of identifying proteoglycan genes expressed in kidney glomeruli, we have performed in situ hybridization for selected proteoglycan core proteins in the normal rat kidney. Syndecan-4, glypican-1 and biglycan were all expressed in normal glomeruli, whereas syndecan-1, perlecan and versican mRNAs were confined to the papillary area. Decorin mRNA was detected in interstitial cells found between tubuli and surrounding larger vessels. No signal for betaglycan mRNA could be detected. By hybridizing adjacent sections with a probe for the podocyte-specific PTPase GLEPP-1, the glomerular cells containing mRNA for syndecan-4 and glypican-1 could be identified as podocytes, whereas the cells expressing biglycan were identified as mesangial cells. These results demonstrate that seven out of the eight proteoglycans investigated are expressed in the normal kidney in detectable amounts and, importantly, that each proteoglycan gene shows a unique pattern of expression. The constitutive expression of syndecan-4, glypican-1 and biglycan in glomerular cells points to a role for these polyanionic molecules in maintaining the integrity of the glomerular filtration barrier.

Amino Acid Sequence↗

PubMed1996

Effects of heparin and aminoguanidine on glomerular basement membrane thickening in diabetic rats.

The effects of heparin and aminoguanidine on glomerular basement membrane thickening were studied in streptozotocin diabetic Sprague-Dawley rats. A placebo-treated group and a non-diabetic group served as controls. All diabetic rats remained severely hyperglycaemic (23 mmol/l) throughout the 8-month study period. At the end of this time relative kidney weight was significantly increased in diabetic control rats (4.9 +/- 0.5 g/kg b.w.) compared with non-diabetic rats (3.3 +/- 0.3 g/kg). This increase was not affected by the intervention treatments. Glomerular basement membrane thickness increased 32% in diabetic control rats (240 +/- 24 nm) compared with non-diabetic rats (182 +/- 20 nm). This increase was prevented by s.c. treatment with both unfractionated and low molecular weight heparins, while basement membrane thickness was the same in animals treated with oral heparins and aminoguanidine and untreated diabetic rats. Macroscopic malignant kidney tumours were seen in three aminoguanidine-treated rats. In conclusion, subcutaneously administered heparin prevents diabetes-induced glomerular basement membrane thickening.

Administration, Oral↗

PubMed1993

Ceftriaxone versus latamoxef in febrile neutropenic patients: empirical monotherapy in patients with solid tumours.

121 patients with 132 febrile episodes were randomised to ceftriaxone or latamoxef monotherapy in order to compare antibiotic efficacy in neutropenic patients treated with cytotoxic chemotherapy for solid tumours. In 80 evaluable episodes no significant differences were observed between the two groups with respect to efficacy and fatal failure rates. Of episodes treated with ceftriaxone, 67% showed a favourable clinical response vs. 61% in the latamoxef group. The clinical response rates in episodes with documented bacterial infections were 67 and 56% in the two treatment groups. In 18% of the episodes with documented initial infections the patients died of presumably uncontrolled infection. The convenient once daily dosage schedule combined with fewer severe adverse reactions favours the use of ceftriaxone instead of latamoxef. Although a relative high degree of response was seen, empirical antibiotic monotherapy apparently does not offer a sufficient antibacterial cover in infections in this type of patient with defective host immunity.

Adult↗

PubMed1992

Effects of thyrotropin-releasing hormone on regional cerebral blood flow in man.

To assess the regional changes in cerebral blood flow, 10 healthy volunteers were given 400 micrograms thyrotropin-releasing hormone iv in a double-blind, randomized, cross-over study. Regional cerebral blood flow was determined simultaneously in two slices of the brain, using a single photon emission computerized tomograph and inhalation of 133Xe. Thyrotropin-releasing hormone caused a significant mean increase of 3.7% (range -8.8-22.7) in blood flow in a region consistent with the left thalamus compared to placebo (3.2% decrease). In 25 other regions no significant change was detected. The thalamic region has previously been shown to be a region especially affected by thyrotropin-releasing hormone in animal studies. The thyrotropin-releasing hormone injection was followed by a minor rise in systemic blood pressure, but not a rise that could affect the cerebral blood flow. The effect of thyrotropin-releasing hormone on the regional cerebral blood flow in the thalamic region was much lower compared to changes found in sedated animals given a hundredfold higher dose of thyrotropin-releasing hormone.

Adult↗

PubMedDate not supplied

Effects of heparin on vascular dysfunction in diabetic rats.

1. Treatment with heparin has beneficial effects in diabetic nephropathy. The occurrence of increased urinary albumin excretion in diabetic patients reflects general vascular dysfunction, including increased transcapillary permeability of macromolecules. The aim of the present study was to evaluate the effects of heparin on vascular dysfunction in diabetic rats. 2. Male Sprague-Dawley rats were used in two studies. Diabetes was induced by 65 mg/kg, i.v., streptozotocin. In one study, diabetic rats were dosed subcutaneously with different heparin fractions for 8 months and the transcapillary escape rate of albumin (TERalb) was measured in anaesthetized animals. In the other study, heparin was given for 6 weeks, followed by tissue albumin clearance measurements in awake rats. Normal and diabetic rats receiving saline served as controls. 3. Blood glucose did not differ among the diabetic groups and ranged from 22 to 26 mmol/L. The mean (+/- SD) TERalb was increased by diabetes compared with values in normal rats (17.5 +/- 3 vs 14.1 +/- 3.3%/h, respectively). Neither unfractionated nor low molecular weight heparin significantly affected this increase. [131I]-Albumin clearance was significantly increased in diabetic rats in the eye, skin and skeletal muscle tissues compared with normal rats (0.17-0.40 vs 0.1-0.23 microL plasma/g per min). Low molecular weight heparin treatment did not affect the increased organ albumin clearance. 4. In conclusion, heparin treatment does not affect diabetes-induced vascular dysfunction as expressed by increased TERalb and clearance of albumin in rats.

Animals↗