Reversibility of disulfide formation. Comparison of chemical and enzyme-mediated reduction of penicillamine and captopril disulfides

The reduction of penicillamine disulfide by reductants in aqueous solutions has been studied and compared with that for captopril disulfide. Whereas near quantitative reduction for captopril disulfide was achieved with tributyl phosphine (200 mM), no detectable penicillamine was formed from penicillamine disulfide. Thiol reductants (25 mM) were, however, partially able to reduce penicillamine disulfide with the most effective agent being glutathione (15% reduction) following by dithioerythritol (8%) and cysteine (5.1%). The reduction of penicillamine-cysteine disulfide by glutathione was 6-fold higher than for penicillamine disulfide. Kinetic analysis showed that the initial rate of reduction and equilibrium constant for the reduction of penicillamine disulfides by glutathione were 267- and 875-fold less than for captopril disulfide at pH 7.4. Biotransformation studies in the cytosol fraction of rat blood cells demonstrated that whereas 48% of the reduction of captopril disulfide was enzyme-mediated only 19% of the penicillamine formed was enzyme-mediated for penicillamine disulfide. Accumulation of disulfides of penicillamine in patients taking penicillamine may therefore be a problem during chronic therapy.     

Biotransformation studies of di-acid angiotensin converting enzyme inhibitors

The biotransformation of di-acid inhibitors of angiotensin converting enzyme was studied in the urine of rats using gas chromatography/mass spectrometry. It was found that after oral administration (10 mg/kg) of enalapril significant amounts (9.2%) of a hydrolytic metabolite of enalaprilat were excreted in urine which was identified as 2-N-alanyl-4-phenylbutanoic acid. This metabolite was present only in trace concentrations in urine after intravenous administration. This pathway was not present, however, with either ramipril or perindopril suggesting that the amide bond in these newer inhibitors is more resistant to hydrolysis than for enalapril. Glucuronidase hydrolysis of urine obtained from rats dosed with either enalapril, ramipril or perindopril indicated the absence of glucuronidate conjugates of these inhibitors in rat urine.     

WATER REQUIREMENT OF PREMATURE NEWBORN INFANTS

Bell, E. F. and Oh, W. (Department of Pediatrics, Women and Infants Hospital of Rhode Island, and the Program in Medicine, Brown University, Providence, Rhode Island, USA). Water requirement of premature newborn infants. Acta Paediatr Scand, Suppl. 305: 21–26, 1983.—Two groups of studies related to the water requirement of premature infants are reviewed. The first examined the effects of several environmental factors on insensible water loss (IWL) and oxygen consumption of 20 low-birth-weight infants. Incubator air temperature above the neutral zone increased IWL, as did the use of a radiant heat source instead of a conventional incubator. A plastic heat shield slightly reduced IWL of infants in incubators. The second group of studies examined the effects of excess water intake in premature infants. 170 infants were randomly assigned to receive "low" (average estimated requirement for birth weight and age) or "high" (excess) volume water intake. The high-volume group became dehydrated less often but had a greater incidence of patent ductus arteriosus and necrotizing enterocolitis.     

The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram

Selective pulmonary arteriography, with superselective magnification views of the lung bases or other areas where abnormalities are shown on perfusion lung scans, performed within 24-48 hours after the onset of symptoms, can effectively rule out clinically significant pulmonary thromboembolism. One hundred and eighty consecutive patients (minimum follow up, six months) with suspected pulmonary embolism and negative pulmonary arteriograms were studied. Not one of the 167 untreated patients died as a result of thromboembolic disease during the acute illness (20 died from unrelated causes), and none of the 147 patients who survived suffered "recurrent embolism" during follow up.     

Reduced natriuresis during weightlessness

Summary The kidney response to weightlessness was measured in one volunteer during a 1-week space mission. Shortly after entering microgravity and later during the mission, consecutive urine sampling periods were monitored, covering in total about 50% of the inflight time. Preflight references were a sequence of ground-based experiments, which evaluated body fluid metabolism with different degrees of standardization. Additional variables, such as circadian rhythms and cortisol-associated stress, were also monitored. In contrast to current hypotheses, the volunteer showed a pronounced reduction in natriuresis and diuresis during the entire space flight, despite a considerable weight loss. For the first time, the urinary excretion of the renal natriuretic peptide urodilatin was also measured. Both, during the preflight experiments and during weightlessness, close correlations between urodilatin excretion and sodium excretion were observed. However, the correlation between natriuresis and urodilatin excretion was considerably altered during weightlessness. We conclude that the loss of body weight during space flight is not related to an increased renal fluid loss and that urodilatin might counteract the decrease in renal excretion observed in weightlessness.     

Effect of a ''centralized intensive education system'' for clean intermittent self-catheterization in patients with voiding dysfunction who start catheterization for the first time

BACKGROUND: This study evaluated the effects of a 'centralized intensive education system' (CIES) in terms of acquiring a proper clean intermittent self-catheterization (CISC) technique by patients with voiding dysfunction. METHODS: Between March 2002 and March 2003, we prospectively and consecutively enrolled 132 hospitalized patients who learnt and started CISC for the first time due to voiding dysfunction. Patients were enrolled either of two groups (the CIES group vs the 'individualized ward education system'[IWES] group) at the time of the urologic consultation for voiding dysfunction. Out of 132 patients who enrolled in the study, 112 (45 males and 67 females, mean age 57.3 with a range of 18-81) were included in the primary analyses. The questionnaire was applied immediately before discharge. RESULTS: There were similar patient demographics and clinical parameters for the CIES (n = 62) and the IWES groups (n = 50). Of 10 items including the methodology of CISC, six items discriminated significantly in favor of the CIES (P < 0.05). The patient satisfaction with CISC education was significantly different for the two groups in terms of response to the questionnaire. The CIES group was found to be more satisfied with the education received than the IWES group (P < 0.05). Moreover, the number of trials to gain confidence to perform CISC in CIES group was significantly fewer than that of IWES group (P < 0.001). CONCLUSION: Our results demonstrate that CIES might be a superior training program for the patients with voiding dysfunction to acquire a proper CISC technique to the conventional IWES.     

Intracranial Stenting Using a Drug-Eluting Stent for Moyamoya Disease Involving Supraclinoid Internal Carotid Artery: A Case Report

A 43-year-old woman was diagnosed with moyamoya disease (MMD) and underwent right-side bypass surgery. After surgery, previous symptoms disappeared. One month later, transient right hemiparetic attacks and motor dysphasia developed. Angiography revealed progressive severe stenosis of left supraclinoid segment of internal carotid artery. Angioplasty using a drug-eluting stent (DES) was performed. For 18 months, she presented no ischemic symptom and no in-stent stenosis was observed in follow-up angiography. This is the first case report about effect of DES use for MMD. Considering that intimal hyperplasia is a pathophysiology of stenosis, DES may have a role in reducing progression of stenosis in selected moyamoya patients.     

Mycotic aneurysms of the aorta: radiologic features

Four patients with a total of six mycotic aneurysms of the aorta were examined with computed tomography (CT) after intravenous contrast material enhancement, and with abdominal or thoracic aortography. In the three patients with mycotic aneurysms involving the abdominal aorta, CT scans showed a vascular paraaortic structure without calcified walls adjacent to a nondilated aorta, and a large non-contrast-enhanced retroperitoneal mass representing inflammatory tissue and blood from a contained aortic rupture. A CT scan of one aneurysm of the thoracic aorta demonstrated an enhanced saccular mass originating from the aorta without paraspinal component. In three of four patients, the CT findings were corroborated by aortographic evidence of an eccentric aneurysmal sac in an atypical location for atheromatous disease. In four patients with clinical manifestations suggesting mycotic aneurysm of the aorta, a combination of CT and angiographic imaging provided accurate diagnostic information for planning adequate and early surgical treatment.