Differences in tocopherol-lipid ratios in ARDS and non-ARDS patients

Plasma tocopherol, plasma total lipid levels and tocopherol-lipid ratio were measured every 6 h during 48 h in 12 critically ill patients and compared with those of a control group. The patients were divided into two groups. Group I comprised 6 critically ill patients with ARDS and group II comprised 6 severely ill patients without ARDS. The means for all observations of plasma tocopherol, total lipid levels and tocopherol-lipid ratio in groups I and II were significantly depressed relative to a control group (p<0.0001). The difference in the average tocopherol-lipid ratio between the three groups (p<0.0001) and between the groups I and II was statistically significant (p<0.0001). Our results indicated: (1) a decrease of vitamin E concentrations in the critically ill patients, particularly in ARDS patients; (2) the importance of the relationship between plasma tocopherol and plasma lipids levels in evaluating the deficiency in vitamin E which was evident in ARDS patients.     

Fos Immunoreactivity after Stimulation or Inhibition of Muscarinic Receptors Indicates Anatomical Specificity for Cholinergic Control of Striatal Efferent Neurons and Cortical Neurons in the Rat

Cholinergic neurons play a major role in the control of striatal activity via muscarinic receptors. The action of acetylcholine also appears to be dependent on the striosome – matrix compartmentalization of the striatum. This study was designed to find out whether modification of acetylcholine tone activates neurons in the striatum and forebrain of the rat. We looked for the appearance of immunoreactivity to Fos, a regulatory protein that is thought to convert synaptic signals into changes in gene expression. Pharmacological manipulation of muscarinic receptors was found to induce specific patterns of Fos immunoreactivity in distinct neuronal populations of the forebrain, including the striatum. Oxotremorine, a non-selective muscarinic agonist, induced Fos immunoreactivity in the striatum with a large predominance in striosomes (mostly in enkephalinergic neurons), in layers 4 and 6 of the cortex, and also in the piriform cortex and septum. The muscarinic agonist pilocarpine had an identical effect in the cortex, but the striosomal prevalence was less clear-cut than that observed after oxotremorine. Treatment with dopamine-depleting agents (6-hydroxydopamine or reserpine) and inhibitors of glutamate and opiate receptor (MK-801 and naloxone respectively) had no effect on the action of oxotremorine. This suggests that the induction of Fos provoked by oxotremorine does not involve dopamine, glutamate or opiates. Atropine, a non-specific muscarinic antagonist, also induced Fos immunoreactivity in the striatum but with matrix predominance (mostly in substance P neurons), as well as in the cingulate cortex, and the olfactory tubercle. Scopolamine, a muscarinic antagonist, induced Fos in both striosomal and matrix compartments in the striatum. No Fos immunoreactivity was observed after change in acetylcholine tone in cholinergic or somatostatinergic neurons of the striatum, or in dopaminergic neurons of the substantia nigra. Our results demonstrate that stimulation or inhibition of muscarinic receptors induces Fos activation in striatal efferent neurons with topological (striosome/matrix) and phenotypical (enkephalin/substance P) prevalence and specificity and also in cortical neurons with also topological prevalence. These data suggest that in humans, direct or indirect modifications of the cholinergic neurotransmission induced by pathological states or by drugs may lead to neuronal events in the forebrain triggered by Fos activation.     

Nutrition-aging influence of catecholamine-promoted lipolysis

Male SPF Fischer 344 rats were fed ad lib. (group A) or 60% ad lib. intake (group R) from 6 wk of age. The group R rats had a markedly increased median length of life. Starting at 6 mo of age, rats were periodically killed and free adipocytes prepared from the epididymal and perirenal depots. The free adipocytes were used for the in vitro study of the effects of age on the promotion of lipolysis by catecholamines. At 6 mo of age, the response of the adipocytes from group A and group R rats was similar when the data are expressed as μmole glycerol released/10⁶ adipocytes. With increasing age, however, this lipolytic response to catecholamines of group A rats markedly declined. The catecholamine-stimulated lipolysis/10⁶ adipocytes from group R rats changed little between 6 and 18 mo of age, and the decline noted after 18 mo of age was less marked than that occurring in adipocytes from group A rats. The data based on rates of lipolysis/10⁶ adipocytes indicate that it is the lifelong nutritional history of a rat population that determines the age-related changes in responsiveness of adipocytes to catecholamines. However, if the data are expressed per sq mm of adipocyte surface, a somewhat different picture emerges. These data are presented and their relevance is discussed.     

Apolipoprotein B immunochemical heterogeneity in dialysed patients with chronic renal failure and patients with coronary artery stenosis

Serum cholesterol, triglyceride, apolipoprotein B (apo B) and the cholesterol and phospholipid content of apo-B-containing particles was determined in 41 male patients on dialysis for chronic renal failure, in 41 male patients with coronary artery disease selected on the basis of a total cholesterol level below 6.72 mmol/l and in 41 male control subjects of similar age. Apo B was assessed as total B protein determined using polyclonal antibodies and also by measuring the expression of epitopes recognized by three different monoclonal antibodies (BL3, BL5 and BL7). Triglyceride was increased (p less than 0.01) and cholesterol was decreased (p less than 0.01) in the dialysed patients with chronic renal failure. Total apo B was similar in the three tested groups while the expression of the BL7 epitope was increased in the group of dialysed patients with chronic renal failure (p less than 0.001). The expression of BL3 and BL5 epitopes was increased in patients with coronary artery disease (BL3: p less than 0.05; BL5: p less than 0.02) but not in dialysed patients with chronic renal failure. These results suggest an abnormal composition and an immunological heterogeneity of apo-B-containing lipoprotein particles in patients with coronary artery stenosis and in dialysed patients with chronic renal failure.     

Improvement of diaphragmatic function by a thoracic extradural block after upper abdominal surgery

The effects on diaphragmatic function of a thoracic epidural block were assessed in 13 patients after upper abdominal surgery (UAS). Lung volumes and tidal changes in chest wall circumferences and gastric (delta Pgas) and esophageal (delta Pes) pressures were measured pre- and postoperatively. Volume displacement of the abdomen divided by tidal volume (delta VAB/VT) and delta Pgas/delta Pes were taken as indices of the diaphragmatic contribution to tidal breathing. These respiratory variables were obtained in the postoperative period, before and after epidural injection of 0.5% plain bupivacaine to achieve a block up to the T4 segment. UAS was constantly associated with a decrease in VT, delta VAB/VT, delta Pgas/delta Pes, and forced vital capacity (FVC). Epidural block was associated with an increase in VT, delta VAB/VT, and FVC. delta Pgas and delta Pgas/delta Pes returned to their preoperative values. It is concluded that: 1) diaphragmatic dysfunction observed after UAS is partially reversed by thoracic epidural block; and 2) that inhibitory reflexes of phrenic activity arising from the abdominal compartment (abdominal wall and/or viscera) could be involved in this diaphragmatic dysfunction.     

Refractory metastatic breast cancer: salvage therapy with fluorouracil and high-dose continuous infusion leucovorin calcium

Sixty women with metastatic breast cancer refractory to at least one chemotherapeutic regimen were treated with fluorouracil (FUra) and high-dose continuous infusion folinic acid (leucovorin calcium). One complete remission lasting 8.7 months and nine partial remissions ranging in duration from 1.3 to 12.8 months were observed, for an objective response rate of 17% (95% confidence interval for response, 8% to 27%). Nine of the ten responding patients had metastatic disease that had objectively progressed on previous chemotherapy with a FUra-containing regimen. This program was well tolerated, with toxicities consisting mainly of stomatitis and granulocytopenia. These results suggest that augmentation of the reduced folate levels of metastatic breast carcinomas may enhance the effectiveness of the fluoropyrimidines in this disease.     

Effects of a one-year administration of phosphate and intermittent calcitonin on bone-forming and bone-resorbing cells in involutional osteoporosis: A histomorphometric study

Summary The bone histomorphometric effects of intermittent phosphate and calcitonin therapy during 1 year were analyzed in 15 involutional osteoporotic patients. Phosphate was administered continuously (1.5 g/day) and calcitonin was injected during 5 days every third week (50 IU/day). The bone cell response was analyzed in two separate groups, according to the amount of trabecular bone present in the iliac bone biopsy: patients with trabecular bone volume (TBV) beyond the histomorphometric spontaneous fracture threshold (0.16 mm3/mm3) (group 1; 11 patients) and patients with TBV above this threshold (group 2; 4 patients). In group 1, the treatment significantly increased TBV from 0.113±0.025 to 0.156±0.046 mm3/mm3 by thickening the existing trabeculae rather than by creating new trabeculae; stimulation of bone formation rate (+50%) and significant reduction in active trabecular resorption surfaces (from 0.021±0.013 to 0.010±0.006 mm2/mm2;P<.05) may have led to positive bone balance. In group 2, TBV was not changed because of the treatment's relative inefficiency for reducing the bone-resorbing cell activity, leading to likely persistent negative bone balance. Cortical thickness did not change in either group. This study confirms the positive effectiveness of continuous treatment with phosphate and intermittent calcitonin during 1 year on bone balance in involutional osteoporosis with low amount of bone. The lack of response in patients with normal amount of bone must be verified before raising the hypothesis of different bone cell activity and before anticipating the therapeutic response according to local bone mass besides bone remodeling status in osteoporosis.