Effects of endurance exercise on the morphology of mouse neuromuscular junctions during ageing

Summary It has been suggested that age changes in the morphology of the neuromuscular junction (NMJ) may reflect altered physical activity levels rather than the unique effects of ageing. Additionally, previous studies have indicated that the structure of the NMJ may be modulated with exercise. To investigate these questions, quantitative morphometry was determined on soleus and extensor digitorum longus (EDL) nerve terminals stained with zinc iodide-osmium from C57BL/6NNia mice under control and endurance exercised conditions at 12, 18 and 24 months of age.As previously observed, the area, perimeter, extent length and branch number of nerve terminals increased with age in both soleus and EDL. The changes were similar between the muscle types, although the changes were more pronounced in the phasic EDL. In 12-month-old animals, 2 months of endurance exercise resulted in significantly larger nerve terminals in both soleus and EDL, suggesting a functional adaptation. Exercised 18- and 24-month-old nerve terminals were smaller than corresponding controls, which indicated that exercise minimized or prevented further age-related nerve terminal elaboration. At all ages the exercised nerve terminals comprised a more homogeneous population than corresponding controls, which indicates that uniform physical activity can modulate NMJ morphometry. The magnitude of the changes suggests that subtle alterations in normal cage activity with advancing age do not have a significant effect on the morphology of nerve terminals. However, the morphology of the NMJ does change significantly in response to physical exercise training.     

Establishment and characterization of a new human Burkitt's lymphoma cell line (WSU-BL)

A new human cell line, WSU-BL, was established from a malignant ascitic fluid occurring in a patient with Burkitt's lymphoma. The established line grows in a single-cell suspension with a doubling time of 19 hours and expresses L3 morphologic features by the French-American-British classification. Immunologic study revealed that WSU-BL cells express IgM-lambda both in the cytoplasm and on the surface and react with monoclonal antibodies to B-cell antigens (B1, B4, BL3, BL4, HLA-DR, and common acute lymphoblastic leukemia antigen [CALLA]). These cells are negative for T-cell and myeloid/monocyte antigens as well as Epstein-Barr virus nuclear antigen (EBNA). These results suggest that WSU-BL corresponds to an intermediate stage of B-cell differentiation. Both fresh tumor and WSU-BL cells had a hyperdiploid karyotype carrying the 8;14 chromosome translocation. Molecular studies showed that WSU-BL has a rearrangement of c-myc proto-oncogene and expresses c-myc RNA. Phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and interferon-gamma (IFN-gamma) were able to induce several phenotypic changes on WSU-BL cells. Two-dimensional gel electrophoresis of total cellular protein showed that either TPA or IFN-gamma induced both the synthesis or loss of several proteins. Analysis of the protein patterns indicated that some proteins were uniquely responsive to either TPA or IFN-gamma and others were common to both. This cell line should be valuable for future studies of cell proliferation, differentiation, and oncogenesis concerning this neoplasm.     

Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

The effect of dopamine on renal function during aortic cross clamping.

Eighteen male patients undergoing elective surgical reconstruction of the abdominal aorta were divided into two groups. Patients in Group I (nine) were given dopamine intravenously, in a dose of 2 micrograms/kg/min, during the first half of the period of cross-clamping, whilst those in Group II received dopamine during the second half. Each patient acted as his own control and for each, three periods were examined, namely: pre-clamp, clamping with dopamine and clamping without dopamine. Dopamine infusion during aortic clamping caused a significant rise in sodium output (P less than 0.01), potassium output (P less than 0.05), creatinine clearance (P less than 0.05) and urine output (P less than 0.05). We conclude that dopamine infusion during aortic clamping helps to protect the kidney from any deleterious effect of clamping.     

Modification of human thrombin: effect on thrombomodulin binding

Thrombomodulin, an endothelial cell protein, binds thrombin with high affinity and alters thrombin from a procoagulant to an anticoagulant molecule. In this study, chemical and/or proteolytic modification of thrombin was carried out to identify the essential components required for its interaction with thrombomodulin. Modification of thrombin at the catalytic site serine and histidine residues, with Diisopropylfluorophosphate and Tosyl-L-lysine chloromethyl ketone, resulted in loss of clotting and amidolytic activity. Both Diisopropyl phosphoryl-thrombin and Tosyl-L-chloromethyl ketone-thrombin inhibited native-thrombin: thrombomodulin catalyzed protein C activation with Ki values of 5 nM and 6 nM respectively indicating no loss of affinity for thrombomodulin. Oxidation of tryptophan residues with N-bromosuccinimide or iodination of tyrosine residues of thrombin led to reduced clotting and amidolytic activity as well as a reduced ability to interact with thrombomodulin. Modification of arginine residues with Phenylglyoxal and 2,3,Butanedione led to loss of thrombomodulin binding affinity. Limited proteolysis of thrombin by trypsin yielded the derivative beta-thrombin which had also lost its ability to interact with thrombomodulin. Deglycosylation of thrombin did not alter its binding affinity for thrombomodulin. These results indicate that one or more tryptophan, arginine and tyrosine residues are essential for the recognition of thrombin by thrombomodulin whilst the carbohydrate side chain and the active site residues of the thrombin molecule are not involved in thrombomodulin binding.     

Oesophageal pemphigus vulgaris

Symptomatic involvement of the oesophageal mucosa by pemphigus vulgaris is rare. We describe 1 patient who was treated with oral steroids during a blistering phase, when epigastric pain developed. Endoscopy revealed multiple ulcerations all over the oesophagus, but gastroduodenal mucosa was normal. The symptoms disappeared following cimetidine for gastro-oesophageal reflux and increase of steroid dosage. When painful symptoms appear from the upper digestive tract during corticosteroid treatment of pemphigus, the possibility of acantholytic involvement of oesophageal mucosa must be kept in mind. Its implication for the dosage of steroids is opposite that in steroid-induced peptic ulcers. Carefully performed upper gastrointestinal tract endoscopy is helpful in these patients.     

Screening of the antiradical action of vegetable oils

Information on radical scavenging activity (RSA) and antioxidant potential of vegetable oils are not reported, or reporting has been rather limited. Such data is of importance for the evaluation of nutritional and health impact of these oils. The main objective of this short study was to compare the antiradical performance of some common and unusual vegetable oils. The described arrangement for our simple experiment uses the addition of stable radicals 1,1-diphenyl-2-picrylhydrazyl (DPPH) to vegetable oils, which are decomposed by components having antioxidant properties. The order of effectiveness of oils in inhibiting free radicals was as follows: coriander>blackcumin>cottonseed>peanut>sunflower>walnut>hemp seed>linseed>olive>niger seed. This initial survey might serve as a springboard for future research into this area.     

Alcohol consumption as a risk factor for hepatocellular carcinoma in urban southern African blacks.

Our purpose was to ascertain whether alcohol abuse is a risk factor for the development of hepatocellular carcinoma in urban southern Africa blacks and, if so, to relate alcohol consumption to other possible risk factors such as persistent hepatitis-B-virus infection, smoking, male sex, in this subpopulation. A prospective, hospital-based, case-control format involving 101 patients with hepatocellular carcinoma and 101 controls was used. The mean age of the patients was 53.7 +/- 1.85 years and the male:female ratio 3.2:1. An increased risk was found, but only in urban men over the age of 40 years who habitually drank more than 80 g of ethanol daily. The risk remained after adjusting for chronic hepatitis-B infection, smoking, and sex (odds ratio 4.4, 95% confidence interval 1.3 to 16.6; p = 0.003). Smoking proved not to be a risk factor, either alone or in concert with alcohol consumption. Hepatitis-B infection was confirmed as a major risk in younger men and in women, but in urban men over the age of 40 years alcohol abuse was a greater risk. Current hepatitis-B infection and alcohol abuse were additive risks.     

Detection of refrigerator-associated 60 Hz alternating current as ventricular fibrillation by an implantable defibrillator.

This report describes a patient with an implantable defibrillator who suffered an inappropriate defibrillation shock upon retrieving some food items from his inadequately earthed refrigerator. Noise typical of electrical interference can be observed in the stored electrogram of the episode. The patient was instructed to earth his home appliances, but he decided to avoid his refrigerator altogether, and has had no subsequent shocks.