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.     

Clinical efficacy of codergocrine mesylate in children with learning difficulties

A double-blind placebo-controlled study in children showed codergocrine mesylate to be effective in improving cognitive functions and behavioural symptoms associated with learning disorders. Forty randomly grouped children of either sex were given an increasing dosage of codergocrine mesylate and followed up for 12 weeks. A significant improvement was noted in speech (acquisition of new words, comprehensibility/meaningfulness of speech), sociability, attention/concentration, comprehension and memory. Improvement in behaviour (emotional lability and cooperativeness) was also noted. Problems of assessing cognitive progress in very young children with culturally appropriate methods were encountered.     

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.     

Reperfused myocardial infarctions on T1- and susceptibility-enhanced MRI: Evidence for loss of compartmentalization of contrast media

The purpose of this study was to characterize the contrast caused by a susceptibility MRI contrast agents, on spin echo T₂-weighted imaging of reperfused myocardial infarction. Our interest in this model focused on the expected requirement that such agents be compartmentalized in the tissue to cause signal loss on spin echo images, a condition which may not be present in reperfused infarcted myocardium. Accordingly, nine rats were subjected to 2 h of left coronary artery occlusion followed by 3 ± 0.5 h of reperfusion prior to administration of contrast media. Three sets of MR images were acquired: (a) baseline axial images at the midventricle, both T₁-weighted (TR/TE = 300/20) and T₂-weighted (TR/TE = 1500/60); (b) T₁-weighted images after administering a T₁-enhancing agent, Gd-DTPA-BMA (0.2 mmol/kg), to document that contrast media is delivered to the reperfused infarction; and (c) T₂-weighted images after administering the susceptibility agent, Dy-DTPA-BMA (1.0 mmol/kg). Gadolinium-enhanced T₁ images depicted reperfused infarction as regions with greatly enhanced signal intensity compared with unin-farcted myocardium, indicating that contrast agent was delivered to the infarcted zone. Dysprosium-enhanced T₁ images depicted the injury as a region of persistent signal intensity relative to depletion of signal in normal myocardium, consistent with failure of the contrast agent to cause signal loss. Similar infarction sizes were observed for unenhanced T₂-weighted images (33 ± 5%), gadolinium-enhanced T₁ weighted images (36 ± 5%) and postmortem staining (30 ± 6%); strong correlations (r > 0.9) were noted in comparisons of these data. Dysprosium-enhanced images exhibited a smaller region of differential signal presumed to be infarction (20 ± 5%, P < 0.05) and weak correlations (r < 0.75) with the other measurements. We conclude that the smaller infarction depicted on dysprosium-enhanced images is a subregion of the true infarction in which myocardial necrosis is sufficiently advanced that the agent is homogeneously distributed throughout all tissue compartments, preventing T₂*-dependent phase loss on spin echo images.     

Laparoscopic flip-flap technique versus conventional inguinal hernia repair in children.

BACKGROUND AND OBJECTIVES: Inguinal hernia repair is one of the most frequently performed pediatric surgical operations. Several pediatric laparoscopic inguinal hernia repair techniques have been introduced. But debate is unresolved regarding the feasibility of laparoscopy for treating pediatric inguinal hernias. METHODS: A retrospective cohort study enrolled 33 patients who underwent congenital inguinal hernia repair by either the new laparoscopic flip-flap technique or conventional open repair. Patients were divided into 2 groups according to the type of surgery: Group A included those who underwent the new laparoscopic technique, and Group B included those who underwent conventional open repair. RESULTS: Group A comprised 15 patients (mean age, 39 months), and group B comprised 18 (mean age, 44 months). Mean operative time was 47.5 minutes for Group A versus 27.5 minutes for Group B. Intraoperative complications for Group A included 1 case (7%) of vas deferens injury, and 3 cases (20%) in which the flaps were torn during suturing. In Group B, no intraoperative complications were encountered. In both groups, the mean postoperative hospital stay was 5.5 hours. Postoperative follow-up of 3 months revealed recurrence in 4 patients in Group A (27%), while there were no recurrences in Group B. CONCLUSION: Our preliminary experience shows unsatisfactory outcomes with laparoscopic flip-flap hernia repair in children. In spite of advancement in the application of laparoscopy in pediatric surgery, conventional open hernia repair is still the gold standard for children, in our experience. Future studies with more numbers and longterm follow-up should be conducted.     

Bench-to-bedside review: Resuscitation in the emergency department

Over the past decade the practice of acute resuscitation and its monitoring have undergone significant changes. Utilization of noninvasive mechanical ventilation, goal-directed therapy, restricted fluid volume, blood transfusion and minimally invasive technology for monitoring tissue oxygenation have changed the practice of acute resuscitation. Early diagnosis and definitive treatment of the underlying cause of shock remains the mainstay for survival after successful resuscitation. Patient-centered outcome end-points, in addition to survival, are being utilized to appraise the effectiveness of treatment. Application of medical ethics to the ever changing practice of acute resuscitation has also become a societal expectation.