Do preservation solutions protect rat cremaster microcirculation during ischemia and reperfusion?

BACKGROUND: Our aim was to investigate the potential of the preservation solution Celsior to protect rat cremaster muscle microcirculation during ischemia and reperfusion, and to compare its effects with those of HTK (histidine-tryptophan-ketoglutarate-Bretschneider solution). Because of its anti-oxidant contents, we expected Celsior to be more protective than HTK. MATERIALS AND METHODS: Capillary perfusion and leukocyte-endothelium interactions were examined in rat cremaster muscle using intravital microscopy. After perfusion with Celsior or HTK (4 degrees C), the cremaster was subjected to 4 or 6 h of warm (33-34 degrees C) ischemia and 2 h of reperfusion. Measurements were performed prior to perfusion and/or ischemia, and 0, 1, and 2 h after restoration of flow. RESULTS: Without Celsior or HTK, capillary perfusion transiently decreased to 50% of baseline after 4 h of ischemia; it remained low (45%) after 6 h of ischemia. Whereas HTK had no significant influence, Celsior deteriorated capillary perfusion: it remained low after 4 h of ischemia (39-48%) and decreased even further after 6 h of ischemia (18-8%). Both preservation solutions similarly reduced the increase in leukocyte-endothelium interactions after ischemia. CONCLUSIONS: Preischemic tissue perfusion with Celsior had an adverse effect on capillary perfusion in rat cremaster muscle after 4 and 6 h of ischemia, whereas HTK did not significantly influence this parameter. Both preservation solutions similarly prevented the increase in leukocyte-endothelium interactions after ischemia. These data suggest that HTK is more suited as a preservation solution for muscular tissue than Celsior, especially when the known protective effects of HTK on muscle function are taken into account.     

Trial of zinc supplements in relation to pregnancy outcomes, hematologic indicators, and T cell counts among HIV-1-infected women in Tanzania

BACKGROUND: In observational studies, the zinc status of HIV-infected persons has been associated with both positive and adverse clinical outcomes. Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women. OBJECTIVE: We examined the effects of zinc supplements on birth outcomes, hematologic indicators, and counts of T lymphocyte subsets among 400 HIV-infected pregnant women. DESIGN: Eligible women between 12 and 27 wk of gestation were randomly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery. All women received iron, folic acid, and multivitamin supplements irrespective of the experimental assignment. RESULTS: We observed no significant differences in birth weight, duration of gestation, or fetal and neonatal mortality between women in the zinc and placebo groups. Hemoglobin concentrations increased between baseline and 6 wk postpartum in both groups. However, the rise in hemoglobin over this period was significantly lower (P = 0.03) in the zinc group (x +/- SD: 11.5 +/- 17.9 g/L) than in the placebo group (15.2 +/- 18.6 g/L). Similarly, the changes in red blood cell count and in packed cell volume over the same period were significantly lower in the zinc group (P < 0.01 and P = 0.01, respectively). Zinc had no effect on CD4(+), CD8(+), or CD3(+) cell counts during the follow-up period. CONCLUSION: Because of the lack of beneficial effects of zinc on adverse pregnancy outcomes and the likelihood of negative effects on hemoglobin concentrations, no compelling evidence exists to support the addition of zinc to prenatal supplements intended for pregnant HIV-infected women.     

Ein neues retrogrades Femurmarknagelsystem mit durchleuchtungsfreier proximaler Verriegelung

INTRODUCTION: Conventional retrograde nailing of the femur causes two important disadvantages: the proximal locking of the nail is difficult because of the anatomic conditions and a chondral defect was left into the knee. MATERIAL AND METHODS: After the retrograde implantation the new nail was lead through the greater trochanter. An additional proximal aiming device for proximal interlocking can be fixed. The entrance portal will be sealed by an osteochondral cylinder. 50 cases of femur fractures were selected for the prospective study. We recorded all intraoperative complications and technical difficulties. The cases were followed up for 52 weeks, both clinical and radiology examinations were performed. RESULTS: The mean follow up was 15.5+/-5 months. All fractures were healed. Knee movement was 125+/-14 degrees. The Leung Score was 84+/-12.6 points; HSS Score was 90+/-9 points. In two cases wound infections were developed. Mal-union was observed in three cases, in two cases nail brake down. CONCLUSIONS: The new retrograde interlocking nail could be used to manage femur fractures successfully. Two aiming devices enable a easy interlocking. Replacement of the osteochondral cylinder into the entry portal reduces cartilage damage.     

Glutaconyl-CoA is the main toxic agent in glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I)

Despite early diagnosis and treatment, 35% of the patients with glutaric aciduria type I (GA I) develop severe neurologic damage. Glutaric acid and 3-hydroxyglutaric acid have been suspected to cause neurodegeneration. Lately, this has been questioned, however. We postulate that glutaconyl Coenzyme A (glutaconyl-CoA) is responsible for brain damage. Chemically, glutaconyl-CoA is an analogue of acrylyl-CoA, the parent substance of the extremely reactive class of acrylates. It is expected to react spontaneously with sulfhydryl groups, thus modifying membranes, disturbing enzyme functions and trapping glutathione. Enhanced production of glutaconyl-CoA together with lack of glutathione precipitates brain damage. Such a mechanism is supported by three findings. (1) The addition product of glutaconyl-CoA to cysteine is present in small amounts in normal human urine. (2) Reaction of methacrylyl-CoA with free sulfhydryl groups has been reported previously in a patient with 3-hydroxyisobutyryl CoA deacylase deficiency. (3) Glutathione has been found to be decreased in homozygous glutaryl-CoA dehydrogenase-deficient knock-out mice.     

The requirement for monocytes in spontaneous cytotoxicity by lymphocytes from healthy donors and melanoma patients

Lymphocytes from 12 healthy donors were depleted of monocytes by velocity sedimentation at unit gravity (average monocyte contamination 0.2%) and tested for spontaneous cytotoxicity (SC) against tumor target cells in 24 h microcytotoxicity assays. Sixty percent of all lymphocytes were recovered in this monocyte-de-pleted lymphocyte fraction (LF). In contrast, with the corresponding unfractionated lymphocytes (UL) the LF cells were not spontaneously cytotoxic on T₂₄ bladder carcinoma, NKI-1, NKI-7, NKI-8, NKI-1O melanoma, and MC-1 mammary carcinoma cell line cells and target cells derived from two short-term melanoma cultures (Me 215 and Me 223). SC of the LF could be restored by reconstitution with autologous monocytes, which were obtained >80% pure in the same velocity sedimentation procedure. Addition of 4–8% monocytes was sufficient to restore the SC of the LF to the level achieved with the corresponding UL, whereas maximal induction of SC was observed after addition of 8–16% monocytes. Higher numbers of monocytes had suboptimal effects. SC of the LF could also be restored by monocyte culture supernatants. The spontaneous cytotoxic effector cells were characterized as non-E rosette-forming, membrane slg-negative Fc-receptor-bearing lymphocytes, a proportion of which probably also bear C₃-receptors. Since the LF was not spontaneously cytotoxic, in spite of the presence of Fc-receptor bearing lymphocytes, it is concluded that monocyte help, mediated via soluble factors, is required. Evidence is presented that the lack of SC by the LF might be attributable to the failure of these cells to make appropriate contact with the target cells. LF/target cell contact followed by target cell kill occurred after addition of monocytes. Effector/target cell contacts, artificially established by agglutinins, did not result in target cell kill. Thus the effector/target cell contacts observed in the presence of monocytes suggest recognition of particular membrane determinants involved in SC. An identical requirement for monocytes was observed with LF cells from 5 stage I and 5 stage II melanoma patients tested for SC against both melanoma and non-melanoma target cells. This indicates that either the cytotoxicity against melanoma cells with lymphocytes from melanoma patients is of the same nature as the SC of lymphocytes from healthy donors, or that specific melanoma-associated cellular cytotoxicity also requires monocyte help.     

Non-invasive imaging of the endocrine pancreas (review)

The non-invasive imaging of the endocrine pancreas is currently considered by concerned institutions as a priority theme of research. Because the endocrine pancreas represents only about one percent of the pancreatic gland, highly specific tools are required for labelling the insulin-producing cells. The present review deals with the possible use of D-mannoheptulose for the non-invasive quantification of insulin-producing cells in the pancreas. This heptose is transported into hepatocytes and insulin-producing cells, but not other cell types, at the intervention of GLUT2. Its uptake coincides with the intracellular accumulation of acidic metabolites generated by phosphorylation of D-mannoheptulose. These metabolites remain in the islet cells after prolonged washing, suggesting that imaging of the pancreas at a relatively late time after intravenous administration of D-mannoheptulose could avoid significant extracellular contamination. Using tritiated D-mannoheptulose as tracer, a new method was designed for quantification of the total mass of insulin-producing cells in either isolated perfused rat pancreata or isolated pancreatic islets. Likewise, a preferential labelling of hepatocytes and insulin-producing transplanted cells can be achieved in vivo after administration of tritiated D-mannoheptulose. In the light of results obtained with 6-deoxy-6-iodo-D-glucose, it is proposed that 7-deoxy-7-iodo-D-mannoheptulose could be used for the non-invasive imaging of the endocrine pancreas.     

Electroconvulsive therapy in Belgium: a questionnaire study on the practice of electroconvulsive therapy in Flanders and the Brussels Capital region

OBJECTIVES: We sought to review and describe the practice of electroconvulsive therapy (ECT) in Flanders and the Brussels Capital region, Belgium, in 2003. METHODS: A 30-item questionnaire was sent to all institutions that provided psychiatric care. Besides questions on training and general attitude toward ECT, most questions concerned technical aspects, quality, and organization of this treatment modality. RESULTS: All psychiatric departments offering ECT and 58% of the hospitals that do not conduct ECT replied to the questionnaire. Forty-three percent of the departments offering ECT indicated less than 10 treatment sessions per month. Forty-three percent of hospitals set a fixed number of treatments per course. Maintenance ECT and ECT on an outpatient basis were rather rare, except for a few departments. The major indication for ECT was depression (88%) rather than schizophrenia (8%), mania (3%), or other psychiatric disorders (1%). Propofol was the anesthetic most commonly used (74%). Seven departments (30%) used a sine wave device. Bilateral electrode placement was the preferred option in 91% of all departments and both fixed high dose and dose titration strategy were used equally (both 47.8%). CONCLUSION: The present findings demonstrate that the practice of ECT in Flanders and the Brussels Capital region in 2003 generally was not performed according to the available guidelines. ECT is underused in Flanders and the Brussels Capital region compared with other countries, although it is available in both specialized psychiatric facilities and in the psychiatric departments of general hospitals.     

Gut Permeability and Intestinal Mucins,Invertase, and Peroxidase in Control and Diabetes-Prone BB Rats Fed Either a Protective or a Diabetogenic Diet

This study deals with the enteropathy recently identified in diabetes-prone BB rats (BBdp). Diabetes-resistant BB rats (BBc) and BBdp rats were fed from days 32–39 onward either a protective diabetes-retardant hydrolyzed casein diet (HC) or a plant-based diabetogenic (NTP) diet. The NTP diet decreased body weight and plasma insulin in BBc and BBdp rats. The BBdp rats displayed low intestinal invertase and increased intestinal peroxidase activity. In the BBdp rats fed the HC diet, the mucin content 30–35 cm below the pylorus was higher and the gut permeability lower than in the other three rat groups. There was a significant inverse correlation between gut permeability and the insulinogenic index in the BBdp rats fed the HC or NTP diet. Thus, in BBdp rats, the HC diet somehow prevents the increase in gut permeability and the decrease in the insulinogenic index otherwise found in some of these diabetes-prone animals.