Nitric oxide status in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular (CVD) morbidity and mortality, mainly due to atherosclerosis. Decreased production or reduced bioavailability of nitric oxide (NO) can result in endothelial dysfunction (ED). Multiple mechanisms are known to cause a state of NO deficiency in patients with CKD. Patients in various stages of CKD grouped as group-1 (CKD stage 1 and 2), group-2 (CKD stage 3 and 4), group-3 (CKD stage 5) and healthy controls were included in the study. Each group of patients and controls comprised 25 subjects. Plasma nitrites, L-arginine, asymmetric dimethyl arginine (ADMA) and citrulline were measured in all the subjects. Patients in all stages of CKD had lower NO and higher ADMA levels compared to controls. Further, group-2 and group-3 patients had lower levels of NO and higher levels of ADMA than group-1 patients. L-arginine levels showed no difference between patients and controls. However, group-3 patients had lower L-arginine levels compared to group-1 patients. Citrulline levels were decreased in group-3 patients. NO production was decreased in patients in all stages of CKD. The decrease could be due to decreased availability of the substrate, L-arginine or due to an increased ADMA, a potent inhibitor of endothelial NO synthase. Therapeutic interventions directed towards improvement of NO production in addition to management of other CVD risk factors may prevent development of ED and facilitate proper management of CKD patients who are at increased risk for CVD.

Stroke in chronic kidney disease.

Chronic kidney disease (CKD) is associated with a higher risk for stroke in studies from developed countries. This prospective study was conducted to study the clinical profile, management, and outcome of stroke in patients of chronic kidney disease who had been admitted in our institute during the period from December 2004 to December 2006. A higher incidence of stroke was found in men and in the fifth decade of life. Hypertension and diabetes were found in 88.8 and 48.1% of the patients respectively. CKD was detected for the first time during stroke evaluation in 55.5% of the patients. Stroke was due to cerebral infarction in 48.14% and due to cerebral hemorrhage in 40.7% of the patients. Surgical intervention was needed in 14.8% of all patients while stroke was managed medically in the rest. Over 70% of the patients were discharged after they showed improvement in the symptoms.

A peptidase activity from primate liver that inactivates oxytocin in vitro: purification and partial characterization.

An aminopeptidase from monkey (Macaca radiata) liver, inactivating oxytocin in vitro and located predominantly in the lysosomal and microsomal fractions, was purified by chromatography on Bio-Gel HTP, DEAE-Sephacel and nickel ion chelate gel and gel filtration on Sephacryl S300. Absence of binding to nickel ion chelate gel indicated the absence of exposed histidine and thiol residues on the enzyme. The enzyme appeared to be a high molecular weight (Mr 106,000) monomeric protein. It was sensitive to inhibition by metal chelators and was found to be a zinc metalloprotein by atomic absorption spectrophotometry. Divalent metal ions Ni2+ and Co2+, and sulphydryl activators glutathione and 2-mercaptoethanol had activating effects, while 4-chloro mercuribenzoate, amino acids with large hydrophobic side chains and L-cystine, beta-lactam antibiotic cloxacillin and peptidase inhibitor amastatin had inhibitory effects on the enzyme activity. The enzyme was most active against S-benzyl L-cysteine 4-nitroanilide substrate. The properties of the enzyme were distinct from those of the well-characterized alanine and leucine aminopeptidases (EC 3.4.11.2 and EC 3.4.11.1 respectively) of liver, and of primate placental cystine aminopeptidases (EC 3.4.11.3).

Impaired polymorphonuclear leukocyte motility in malnourished infants: relationship to functional abnormalities of cell adherence.

The humoral and cellular contributions to PMN motility in vitro were studied in 37 malnourished (PCM) pediatric patients. Early-phase directed migration to BCF and to ZANS was diminished significantly (p less than 0.001) in severe PCM patients as compared to healthy adult or age-matched controls or respective nutritionally restored patients. Abnormalities were reversible after nutritional restoration and unrelated to occurrence of clinical infection. To determine the pathogenic mechanism of impaired PMN mobility in PCM, studies of cell morphology and adhesive function were performed. Abnormalities observed in severe PCM suspensions included significantly (p less than 0.001) increased baseline (unstimulated) adherence values and impaired CF modulation of adhesive function. Diminished enhancement of PMN adherence or decreased (relative to baseline) adherence values were observed in response to BCF (mean % delta = +5) or f-Met-Leu-Phe (mean % delta = -6) as compared to adult PMN values of +28% delta and +31% delta, respectively. That these abnormalities may result from in vivo CF prestimulation was suggested by findings of "activated" PMN morphology in suspensions prior to in vitro stimulation, and abnormalities of the distribution of PMN surface adhesion sites under conditions of chemotactic stimulation. Further investigations will be required to determine the underlying pathogenic mechanism(s) accounting for our observations.