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Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 361 records · Page 20Linked to original sources

The molecular basis of increased glomerulosclerosis after blockade of the renin angiotensin system in growth hormone transgenic mice.

BACKGROUND: Angiotensin converting enzyme inhibitor (ACEi) therapy delays the onset of renal failure in diabetic nephropathy and inhibits or delays the onset of proteinuria in several animal models. MATERIALS AND METHODS: We examined this question using a transgenic model of chronic glomerulosclerosis caused by an excess production of growth hormone (GH) in which there is progressive glomerular scarring leading to uremia. In addition, since GH mice do not have systemic hypertension or an elevated glomerular filtration rate, we could address the question of whether ACEi or angiotensin II receptor antagonists (AII RA) had an effect on the development of glomerulosclerosis under these conditions. Since excess matrix accumulates in glomerulosclerosis because of alterations in the balance between its synthesis and degradation, we examined the effect of ACEi and AII RA on these parameters. RESULTS: Systemic blood pressure was unaffected by ACEi treatment, but the glomerular filtration rate decreased 85%. ACEi-treated mice had increased mesangial deposition of type I collagen and decreased 105 kD complex collagenase activity. In addition, ACEi-treated GH mice had increased glomerular alpha 1 type I collagen, alpha 1 type IV collagen, and alpha-smooth muscle cell actin mRNAs. No changes were noted in beta actin, or 72 kD metalloproteinase mRNAs. The result of these changes was a net increase in sclerosis. Surprisingly, GH mice treated with ACEi or AngII RA developed marked renal arteriolar lesions. CONCLUSIONS: In some forms of glomerulosclerosis, the lesions develop independently of angiotensin II. Pharmacological inhibition of angiotensin II, in this circumstance, may aggravate the lesions through disregulation of the levels and the balance between glomerular matrix synthesis and degradation.

Actins↗

Characterization of [125I]RTI-55 binding to dog caudate dopamine transporter.

We have characterized binding of [125I]RTI-55 ((-)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) to the dog caudate membrane and detergent solubilized dopamine transporter sites. The solubilized transporter was assayed by filtration over polyethylenimine treated Whatman GF/B filters. [125I]RTI-55 specifically binds to transporter sites in membranes and solubilized protein with Kd of 0.27 and 0.34 nM, respectively. The binding of [125I]RTI-55 to the membrane and solubilized transporter was inhibited by dopamine, norepinephrine and serotonin uptake inhibitors with rank order and potencies consistent with that of the dopamine transporter. Thus, similar pharmacological properties between membranes and solubilized dopamine transporters were retained upon solubilization. Rapid assay of solubilized protein will aid in monitoring transporter protein purification.

Animals↗

An outbreak of echovirus type 4 infections and its implications for diagnosis and management in general practice.

Altogether, 133 patients with Echovirus type 4 infection were studied. Presenting illnesses and reasons for referral to hospital were analyzed. The reason for admission was commonly concern about meningitis, but also an unexplained rash or sore throat. More research is needed in general practice in order to clearly elucidate the spectrum of disease caused by Echoviruses.

Adolescent↗

On the frequency and reproducibility of orthostatic blood pressure changes in healthy community-dwelling elderly during 60-degree head-up tilt.

The postural effects of 20 minutes of 60-degree head-up tilt on systolic, diastolic, and mean arterial blood pressures (BPs), heart rate, and rhythm were studied in 70 healthy, community-dwelling volunteer subjects of both sexes, divided into three age groups. Group A consisted of 30 subjects, with a mean age of 76 years (range 65 to 95 years); group B had 19 subjects, with a mean age of 54 years (range 45 to 64 years); and group C had 21 subjects, with a mean age of 33 years (range 24 to 44 years). To qualify, subjects had to have a systolic BP of 150 mm Hg or less and a diastolic BP of < 90 mm Hg, be taking no prescribed medications, have had no previous syncopal episodes, and have absence of any significant medical illness. Nine of 30 (30%) subjects in group A, 1 of 19 (5%) subjects in group B, and 2 of 21 (9.5%) subjects in group C exhibited asymptomatic postural drops in systolic blood pressure > 20 mm Hg (p < 0.05). The mean time for the systolic blood pressure drops in group A was 9.2 minutes. Results were reproducible upon retesting after 1 week.

Adult↗

Inhibitors of enkephalin-degrading enzymes as potential therapeutic agents.

A limited number of enzymes such as membrane metalloendopeptidase (enkephalinase) and angiotensin converting enzyme appear to be involved in deactivation and modulation of circulatory regulatory peptides. Peptides such as the enkephalins are also involved in a large number of physiological processes. This multiplicity of physiological roles has made it difficult to establish the therapeutic role of enkephalin-degrading enzyme inhibitors. Other factors such as difficulty in quantification and thus measurement of processes involved in pain and mental illness have also hindered the process of establishing any therapeutic role of enkephalin-degrading enzyme inhibitors in these conditions. However, they have proved to be useful pharmacological 'tools'. The most likely therapeutic role at present appears to be in the treatment of cardiovascular disorders. As a 'profile' of pharmacological actions of enkephalin-degrading enzymes emerges, it is becoming apparent that bioavailability rather than a high degree of specificity or inhibitory potency may be the most important factor. This may be used to an advantage in future developments by the use of less specific or combined inhibitors in the form of prodrugs, designed to be active at specific sites such as the central nervous system.

Aminopeptidases↗

Comparison of the haemodynamic effects of enoximone and piroximone in patients after cardiac surgery.

We have compared the haemodynamic effects of the imidazole derivative phosphodiesterase inhibitors enoximone and piroximone in patients with low cardiac output after cardiac surgery. Ten patients (group E) received enoximone and 10 patients (group P) received piroximone, both at a loading dose of 0.5 mg kg-1 followed by an infusion of 5 micrograms kg-1 min-1. In both groups the main changes with time were increases in cardiac index (maximum 24.5% in group E, 25.8% in group P) and decreases in systemic vascular resistance (maximum 26.8% in group E and 24.8% in group P). There were moderate increases in heart rate (maximum 11.3% in group E and 13% in group P) but a greater percentage decrease in mean arterial pressure in group E (maximum 11.9% vs 7.9%) with time. One patient in group E developed hypertension during the loading dose. Two patients in group E and two in group P developed hypotension during the loading dose. One patient in group E developed ventricular extrasystoles which may have been related to the drug being studied.

Aged↗

Species differences in dopamine transporters: postmortem changes and glycosylation differences.

The apparent molecular masses of photoaffinity-labeled dopamine transporters (DATs) from rat, human, dog, and primate kidney COS cells expressing the rat DAT1 cDNA differ. Sequences predicted from cDNA cloning reveal only one amino acid difference between the length of the rat and human DAT but one less site for potential N-linked glycosylation in the human DAT. Possible posttranslational and postmortem bases for species differences in DAT molecular mass were explored. Rat DAT proteins from striata subjected to approximately 5 h of postmortem delay modeled after the human postmortem delay process revealed small but consistent losses in apparent molecular mass and in cocaine analogue binding; the DAT molecular mass displayed no further losses for up to 30 h of model postmortem treatment. Degradative postmortem changes could thus contribute to molecular mass differences between rat and human DATs. Neuraminidase treatment reduced the apparent molecular mass of native rat DAT but not that of the rat DAT expressed in COS cells, suggesting that the sugars added to the DAT expressed in COS cells were different than those added to the rat brain striatal transporter. These differences could account for the somewhat higher Km values for expressed DAT cDNA in COS cells when compared with the wild-type striatal transporter. These results are in accord with the differences in number of predicted N-linked glycosylation sites between rat and human DATs and with cell-type specificity in transporter posttranslational processing.

Affinity Labels↗

L-arginine administration normalizes pressure natriuresis in hypertensive Dahl rats.

A blunted pressure-natriuretic response characterizes hypertension in the Dahl salt-sensitive rat. Long-term L-arginine administration prevents hypertension in these animals. To determine if long-term L-arginine corrects the pressure-natriuretic response, we gave salt-sensitive rats on an 8% sodium diet L-arginine or vehicle daily for 3 weeks. Identically treated salt-resistant rats served as controls. After 3 weeks, acute pressure-natriuresis curves were determined. To control for hypertension-induced renal damage, we also examined pressure natriuresis in salt-sensitive rats after short-term L-arginine. Baseline mean arterial pressure was 158 +/- 3 mm Hg in vehicle-treated salt-sensitive rats and 127 +/- 3 mm Hg in chronically L-arginine-treated salt-sensitive rats. During alterations in perfusion pressure, renal blood flow was autoregulated in all groups. Glomerular filtration rate was autoregulated in salt-resistant rats and L-arginine-treated salt-sensitive rats but fell with decreasing pressure in vehicle-treated salt-sensitive rats. Sodium excretion was greater (P < .05) in L-arginine-treated than in vehicle-treated salt-sensitive rats and did not differ from salt-resistant rats at 100, 125, and 158 mm Hg. The slope of the pressure-natriuresis relation was greater (P < .05) in chronically L-arginine-treated than in vehicle-treated salt-sensitive rats. L-Arginine had no effect on natriuresis in salt-resistant rats. Thus, long-term L-arginine administration normalizes pressure-natriuretic responses in salt-sensitive rats. The effect is not due to the prevention of renal damage and is specific to the salt-sensitive strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Electric injury with cerebral venous thrombosis. Case report and review of the literature.

BACKGROUND AND PURPOSE: A case of accidental electrocution with previously unreported arteriographic evidence of cerebral vein thrombosis is presented. A brief description of early and late neurological complications and current theories attempting to explain the histopathological findings of electric injury are reviewed. The occurrence and persistence of late neurological complications are elucidated. CASE DESCRIPTION: A report of an accidental electrocution with 800 V of alternating current in a young man is presented. Cerebral angiography showed a cerebral vein thrombosis. The immediate complications included loss of consciousness, confusion, memory loss, and headache. Late complications of right-sided clumsiness, sensory loss, hemianopsia, and neglect persisted for more than 1 year despite the brain being outside the current pathway. CONCLUSIONS: High-voltage electric injury may cause cerebral vein thrombosis with significant early and delayed brain injury even when the brain lies outside the current pathway.

Adult↗

Serodiagnosis of extrapulmonary tuberculosis by ELISA.

This study aims at evaluating the specificity and sensitivity of ELISA test in detection of Mycobacterial Antibodies using A60 antigen. Sera from 100 clinically suspected cases of extrapulmonary tuberculosis were studied along with 10 sputum positive cases 25 age and sex matched healthy control. Overall positivity of the test was 80.00 per cent with 100 percent sensitivity and 92 per cent specificity. The present study recommends ELISA as an adjunct to other investigative procedures.

Antibodies, Bacterial↗

Advance directives for HIV-positive patients.

The authors surveyed HIV-positive patients to determine their knowledge of and interest in advance directives and their preferences for end-of-life care. The results of this study make clear the need to institute a program of education for those desiring to know more about advance directives.

Adult↗