Relationship between digestive and killing abilities of neutrophils against Paracoccidioides brasiliensis.

Peripheral blood neutrophils (PMN) from patients with paracoccidioidomycosis killed and digested Paracoccidioides brasiliensis much less than did PMN from normal individuals or from patients with other diseases. However, deficiency in killing ability was less specific than digestive deficiency and correlated poorly with it. We conclude that the capacities of PMN to digest and kill P. brasiliensis are not intimately related phenomena, and that in paracoccidioidomycosis the key deficiency of neutrophil function is that of digestion of P. brasiliensis.     

Cost–Utility Analysis of Paclitaxel in Combination with Cisplatin for Patients with Advanced Ovarian Cancer

The standard treatment for patients with advanced ovarian cancer (AOC) has been cyclophosphamide and cisplatin (CP). Recently, the results of a large randomized comparative trial demonstrated that the combination of paclitaxel and cisplatin (TP) provided a progression-free survival benefit of 5 months. In this study, a cost–utility analysis was performed from a Canadian health care system perspective to estimate the incremental cost-effectiveness of the TP combination. Twelve AOC patients who received treatment with TP were matched for age and disease stage on a 1-to-2 basis with a CP control. Total hospital resource consumption was then collected for all patients. Treatment preferences were estimated from a cohort of 20 patients and 40 healthy female volunteers using the time trade-off technique. The outcomes were then generated through a decision-analytic model. First-line treatment costs with TP were approximately fourfold greater on a per-cycle basis than the CP alternative (Can$1911 vs Can$459). When progression-free survival benefit and patient treatment preferences were incorporated into the analysis, the results of the decision model revealed an incremental cost between Can$12,000 and Can$24,000 per quality-adjusted progression-free year with the TP protocol. Even though the TP combination has a considerably higher drug acquisition cost, the results of the current analysis suggest that this new chemotherapy regimen does provide patients with substantial quality-adjusted progression-free survival benefit at a reasonable cost to the Canadian health care system.     

Carcinogenesis in rats by nitrosodialkylureas containing methyl and ethyl groups given by gavage and in drinking water

The carcinogenic effects in male and female F344 rats of four nitrosodialkylureas containing methyl or ethyl groups have been compared by two modes of administration, gavage in oil solution or dissolved in drinking water. Weekly doses of 20 and 40 mumol were given to each rat by either route and treatment lasted usually 30 wk, resulting in a total dose per rat of 0.6 or 1.2 mmol. Nitrosodimethylurea and nitroso-1-methyl-3-ethylurea gave rise primarily to tumors of the nervous system, whereas nitrosodiethylurea and nitroso-1-ethyl-3-methylurea gave rise to tumors of the mammary gland, lung, intestinal tract, nervous system, and testicular mesotheliomas. The effect of nitrosodimethylurea was weaker than that of the other three compounds, as measured by rate of mortality with tumors. Drinking water treatment was less effective than treatment by gavage, by the same criterion. The tumorigenic effects paralleled those of the corresponding monoalkylnitrosourea, suggesting the presence in the target organs of receptors for which ethylnitrosoureas or methylnitrosoureas, respectively, have affinity.     

Phospholipid determination in platelets,plasma and red cells of patients with chronic myeloproliferative disorders

Abstract: Red cell phospholipids (PLs) were assessed in 11 patients with essential thrombocythemia and 5 patients with polycythemia vera. Platelet and plasma PLs were also determined in 10 of these patients, and the results were compared with studies performed in 16 healthy volunteers. The amount of platelet PLs in patients was similar to controls (556 ± 90 nmol/10⁹cells, versus 481 ± 91 nmol/10⁹cells), as was the percentage of the main specimens of these compounds, including phosphatidylserine (11.1 ± 0.8%), which is relevant for platelet procoagulant activity. We did not find differences between red cell PLs of patients (300 ± 60 nmol/10⁹cells), versus controls (289 ± 71 nmol/10⁹cells), and the sphingomyelin/phosphatidylcholine ratio in these cells was the same in both groups (0.75 ± 0.1). Finally, we did not detect any alteration in the amount of plasma PLs specimens.     

Intravenous magnesium sulphate effect on maternal serum and amniotic fluid cytokines levels in preterm labour patients.

Our objective was to evaluate the effect of intravenous magnesium sulphate administration to patients with preterm labour on maternal serum and amniotic fluid IL-1beta, IL-6, IL-10 and TNFalpha concentrations. Thirty-six patients at 24-34 weeks of singleton gestation, who presented with contractions (> or = 8 in 60 min) had amniocentesis to rule out intrauterine infection. The patients received intravenous MgSO4 for tocolysis. Twenty-six patients had amniocentesis performed before initiation of MgSO4 (controls) while 10 others had the procedure during tocolytic therapy (study patients). Magnesium, IL-1beta, IL-6, TNFalpha and IL-10 concentrations were measured. Study and control groups were statistically compared using Student t test. Mean magnesium levels were significantly higher in the study group (P < 0.01). There were no significant differences between the cytokines levels in maternal serum and in amniotic fluid between the groups. Our results suggest that the mechanism of magnesium as a tocolytic agent may not be mediated via the examined cytokines.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Risk factors for asthma in adolescents in a large urban region of Brazil.

BACKGROUND: Identify risk factors for asthma in adolescents from S?o Paulo, Brazil. METHODS: total of 528 adolescents (141 asthmatics, 387 control subjects) from the ISAAC study (phase III) were submitted to a complementary questionnaire to evaluate risk factors, through response to questions regarding personal history, environment, and diet and an agreement to undergo the skin prick test (SPT) for aeroallergens. RESULTS: Positive SPT to at least one allergen occurred in 49.4% adolescents. The risk factors for asthma were: prematurity (OR: 3.84, 95% CI: 1.54-9.64), rhinitis (OR: 3.18, 95% CI: 1.71-5.91), positivity in the SPT (OR: 2.81, 95% CI: 1.48-5.32), eczema in characteristic skin-folds (OR: 2.86, 95% CI: 1.13-7.26), and an allergic mother (OR: 2.01, 95% CI: 1.02-3.93). The consumption of cooked vegetables was a protective factor for asthma (OR: 0.37, 95% CI: 0.18-0.79) CONCLUSIONS: Asthma is a multifatorial disease. An allergic mother, aeroallergen sensitization, rhinitis, eczema and prematurity were considered risk factors and the consumption of cooked vegetables was considered a protective factor for asthma in this population.     

Immunohistological study of grumose degeneration of the dentate nucleus in progressive supranuclear palsy

The grumose degeneration observed in the dentate nuclei of 7 cases of progressive supranuclear palsy (PSP) was studied with a panel of antibodies which included 2 neurofilaments, Tau and ubiquitin. Dentate nucleus neurons were negative with all antibodies except ubiquitin which showed a slightly positive homogeneous pattern of staining. The amorphous material surrounding swollen or normal neurons was strongly positive for neurofilament and subunits and numerous torpedoes were observed in the granular layer of the cerebellar cortex. Our results confirm that grumose degeneration consists in degeneration of terminal axons of Purkinje cells in the dentate nucleus. The positivity of dentate nucleus neurons for ubiquitin may support the concept of synaptic dysfunction between Purkinje cells and dentate nucleus neurons.