IL-4 receptor expression on CD8+ T cells is required for the development of protective memory responses against liver stages of malaria parasites

IL-4 receptor (IL-4R)-deficient CD8+ T cells specific for the circumsporozoite protein of Plasmodium yoelii develop a severely impaired memory response after priming with parasites. Memory CD8+ T cells lacking the IL-4R are unable to establish a stable population residing in nonlymphoid organs, although they develop normally in lymphoid organs. Because memory cells from nonlymphoid organs disappear shortly after immunization, the protective antiparasitic activity of this T cell response also is lost. These results demonstrate that IL-4/IL-4R interactions on CD8+ T cells play a critical role in modulating the development and tissue distribution of memory cells induced by parasite immunization. They also indicate that memory cells residing in nonlymphoid tissues are critical for protective immunity against malaria parasites

The behavior of kinetic parameters in production of pectinase and xylanase by solid-state fermentation

AbstractSolid-state fermentation (SSF) is defined as the growth of microbes without a free-flowing aqueous phase. The feasibility of using a citrus peel for producing pectinase and xylanase via the SSF process by Aspergillus niger F3 was evaluated in a 2kg bioreactor. Different aeration conditions were tested to optimize the pectinase and xylanase production. The best air flow intensity was 1VkgM (volumetric air flow per kilogram of medium), which allowed a sufficient amount of O2 for the microorganism growth producing 265U/g and 65U/g pectinases and xylanases, respectively. A mathematical model was applied to determine the different kinetic parameters related to SSF. The specific growth rate and biomass oxygen yield decreased during fermentation, whereas an increase in the maintenance coefficient for the different employed carbon sources was concurrently observed

Comparative Bioavailability Of Two Quetiapine Formulations In Healthy Volunteers After A Single Dose Administration

The study was performed to compare the bioavailability of two quetiapine 25 mg tablet formulations: the test formulation was quetiapine fumarate (kitapen®) manufactured by Cobalt Pharmaceuticals, Canada/ Arrow Farmacêutica Ltda* (Erowlabs). Seroquel® (quetiapine) from Astrazeneca Brazil was used as reference formulation. The study was conducted open with randomized two period crossover design and one week wash out period in 64 volunteers of both sexes. Plasma samples were obtained over a 48 hour interval. Quetiapine was analyzed by LC-MS-MS in the presence of quetiapine-D8 as internal standard. Plasma samples were obtained over a 48 hour interval. Quetiapine was analyzed by LC-MS-MS in the presence of quetiapine-D8 as internal standard. The mean ratio of parameters Cmax and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the bioequivalence. The means AUC 0-t for test and reference formulation were 432.41 ng.h/mL and 412.20 ng.h/mL, for AUC 0-∞ were 440.06 ng.h/mL and 418.90 ng.h/mL and, for Cmax 126.94 ng/mL and 108.71 ng/mL, respectively. Geometric mean of quetiapine (kitapen®)/Seroquel® 25 mg individual percent ratio was 97.68% AUC 0-t, 97.47% for AUC 0-∞ and 90.68% for C max. The 90% confidence intervals were 92.67 - 102.96%, 92.53 - 102.67%, 83.37 - 98.64%, respectively. Since the 90% confidence intervals for C max, AUC 0-t and AUC 0-∞ were within the 80 - 125% interval proposed by Food and Drug Administration, it was concluded that quetiapine (kitapen®) 25 mg tablet was bioequivalent to Seroquel® 25 mg tablet according to both the rate and extent of absorption. © 2011 Junior EA, et al.38178181Barrett, B., Capek, H.M., Huclova, J., Borek-Dohalsky, V., Fejt, P., Validated HPLC-MS/MS method for determination of quetiapine in human plasma (2007) Journal of Pharmaceutical and Biomedical Analysis, 44, pp. 498-505DeVane, C.L., Nemeroff, C.B., Clinical Pharmacokinetics of quetiapine: An Atypical Antipsychotic (2001) Clinical Pharmacokinet, 40, pp. 509-522Kasper, S., Müller-Spahn, F., Review of quetiapine and its clinical applications in schizophrenia (2000) Expert Opin Pharmacother, 1, pp. 783-801Tilden, D., Aristides, M., Meddis, D., Burns, T., An economic assessment of quetiapine and haloperidol in patients with schizophrenia only partially responsive to conventional antipsychotics (2002) Clin Ther., 24, pp. 1648-1667Mario, A., Michael, E., The Role of Quetiapine Extended Release in the Treatment of Bipolar Depression (2010) Adv Ther, 27, pp. 1-11Keck, P., McIntyre, R., Shelton, R., Bipolar depression: Best practices for the outpatient (2007) CNS Spectr., 12, pp. 1-16Judd, L., Akishal, H., Schettler, P., The long-term natural history of the weekly symptomatic status of bipolar I disorder (2002) Arch Gen Psychiatry., 59, pp. 530-537Goldstein, J.M., Atypical antipsychotic drugs: Beyond acute psychosis, new directions (1999) Emerging Drugs, 4, pp. 127-151Abi-Dargham, A., Laruelle, M., Aghajanian, G.K., Charney, D., Krystal, J., The role of serotonin in the pathophysiology and treatment of schizophrenia (1997) J Neuropsychiatry Clin Neurosci, 9, pp. 1-17Kapur, S., Remington, G., Serotonin-dopamine interaction and its relevance to schizophrenia (1996) Am J Psychiatry, 153, pp. 466-476Calabrese, J.R., Keck Jr., P.E., McFadden, W., Minkwitz, M., Ketter, T.A., Weisler, R.H., Cutler, A.J., Mullen, J., A randomized, doubleblind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression (2005) Am J Psychiatry, 162, pp. 1351-1360Copolov, D.L., Kowalcyk, B., A multicentre, double-blind, randomized comparison of quetiapine and haloperidol in schizophrenia (2000) Psychol Med, 30, pp. 95-105Figueroa, C., Brecher, M., Hamer-Maansson, J., Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release (2009) Prog Neuropsychopharmacol Biol Psychiatry, 33, pp. 199-204Goldstein, J.M., Litwin, L.C., Sutton, E.B., Malick, J.B., Seroquel: Electrophysiological profile of a potential atypical antipsychotic (1993) Psychopharmacology, 112, pp. 293-298Kasper, S., Tauscher, J., Küfferle, B., Barnas, C., Pezawas, L., Dopamine and serotonin-receptors in schizophrenia: Results of imaging-studies and implications for pharmacology in schizophrenia (1999) Eur. Arch. Psychiatry Clin. Neurosci., 249, pp. 83-89Peuskens, J., A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia (1997) Acta Psychiatr Scand, 96, pp. 265-273Saller, F., Salama, A.I., Seroquel: Biochemical profile of a potential atypical antipsychotic (1993) Psychopharmacology, 112, pp. 285-292Thase, M.E., McFadden, W., Weisler, R., Efficacy of quetiapine monotherapy in bipolar I and II depression: A double-blind, placebo-controlled study (2006) J Clin Psychopharmacol, 26, pp. 600-609Vieta, E., Mullen, J., Brecher, M., Paulsson, B., Jones, M., Quetiapine monotherapy for mania associated with bipolar disorder: Combined analysis of two international, double-blind, randomised, placebo-controlled studies (2005) Curr Med Res Opin, 21, pp. 923-93

Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects

Quadriplegic subjects present extensive muscle mass paralysis which is responsible for the dramatic decrease in bone mass, increasing the risk of bone fractures. There has been much effort to find an efficient treatment to prevent or reverse this significant bone loss. We used 21 male subjects, mean age 31.95 ± 8.01 years, with chronic quadriplegia, between C4 and C8, to evaluate the effect of treadmill gait training using neuromuscular electrical stimulation, with 30-50% weight relief, on bone mass, comparing individual dual-energy X-ray absorptiometry responses and biochemical markers of bone metabolism. Subjects were divided into gait (N = 11) and control (N = 10) groups. The gait group underwent gait training for 6 months, twice a week, for 20 min, while the control group did not perform gait. Bone mineral density (BMD) of lumbar spine, femoral neck, trochanteric area, and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline, and deoxypyridinoline) were measured at the beginning of the study and 6 months later. In the gait group, 81.8% of the subjects presented a significant increase in bone formation and 66.7% also presented a significant decrease of bone resorption markers, whereas 30% of the controls did not present any change in markers and 20% presented an increase in bone formation. Marker results did not always agree with BMD data. Indeed, many individuals with increased bone formation presented a decrease in BMD. Most individuals in the gait group presented an increase in bone formation markers and a decrease in bone resorption markers, suggesting that gait training, even with 30-50% body weight support, was efficient in improving the bone mass of chronic quadriplegics.1357136

Tratamento térmico do leite acondicionado em filme plástico em banho-maria

O presente trabalho foi realizado com a finalidade de se conseguir um procedimento de pasteurização prático e de baixo custo para pequenos produtores de leite, assegurando assim um aumento do tempo de conservação e consequentemente de comercialização do produto, sem riscos para o consumidor. Para tal, amostras de leite já acondicionadas em filme plástico (l litro) foram submetidas a diferentes tratamentos térmicos, sempre utilizando-se banho-maria a 70 ± 1,0°C e variando-se os tempos de exposição. Os resultados obtidos se mostraram satisfatórios sob o ponto de vista físico-químico e microbiológico, reduzindo drasticamente em pouco tempo de exposição a população microbiana e eliminando totalmente as bactérias coliformes totais e fecais presentes no leite cru.In this study one litre plastic bags, filled with raw milk were submited to heat treatments in water bath at 70 ± 1,0°C. The time of treatment varied from 5 to 25 minutes. The results found showed that the heat treatments did not affect the physical-chemical properties of milk at any time and reduced the total microbial population at levels compatible with the Brazilian legal standards and eliminated completely total and feacal coliforms present in the raw milk

Distributed situation awareness in nuclear, chemical, and maritime domains

The increase in size, automation and complexity of modern sociotechnical systems changed the dynamics of work environments and calls for new methodologies and metaphors towards safety of complex systems. Chemical, nuclear, and transportation (i.e. road, maritime, and aviation) industries are composed of various nested sub-systems where smooth coordination and communication are essential features to achieve continuous and safe operations. Even though such sub-systems exist since the industrial revolution, fewer studies have been conducted in these domains: to understand the work as it is done (rather than it is imagined), which is the only way to shed light about the variability in work performance and how these subsystems can combine to generate dangerous and unexpected outcomes. The theoretical framework of Distributed Situation Awareness provides a firm background to investigate the sub-systems that constitute the chemical, nuclear, and maritime industries/domains. This paper unfolds the key sub-systems (e.g., operators, human-computer interfaces, communication tools, and distant/different locations) that play a critical role in normal and abnormal situations in these industries. The complex interconnections among various artifacts are explained and their significance is assessed

Rational design of a (S)-selective-transaminase for asymmetric synthesis of (1S)-1-(1,1′-biphenyl-2-yl)ethanamine

Amine transaminases offer an environmentally sustainable synthesis route for the production of pure chiral amines. However, their catalytic efficiency toward bulky ketone substrates is greatly limited by steric hindrance and therefore presents a great challenge for industrial synthetic applications. We hereby report an example of rational transaminase enzyme design to help alleviate these challenges. Starting from the Vibrio fluvialis amine transaminase that has no detectable catalytic activity toward the bulky aromatic ketone 2-acetylbiphenyl, we employed a rational design strategy combining in silico and in vitro studies to engineer the transaminase enzyme with a minimal number of mutations, achieving an high catalytic activity and high enantioselectivity. We found that, by introducing two mutations W57G/R415A, detectable enzyme activity was achieved. The rationally designed variant, W57F/R88H/V153S/K163F/I259M/R415A/V422A, showed an improvement in reaction rate by more than 1716-fold toward the bulky ketone under study, producing the corresponding enantiomeric pure (S)-amine (enantiomeric excess (ee) value of >99%)

Environmental heterogeneity caused by anthropogenic disturbance drives forest structure and dynamics in Brazilian Atlantic Forest

We evaluated how tree community floristic composition, forest structure and dynamics varied over a period of 13 years across a topographic gradient of ravines created by anthropic disturbance in Brazilian Atlantic Forest. The study area is located within a fragment of Atlantic Forest (21° 09' S, 44° 54' W), in Minas Gerais state, Brazil. This work was based on data of tree diameter at 1.3 m from the soil, collected in four inventories. Each individual was recorded as being in one of three stratified topographic classes: hilltop, slope and bottom. We used direct gradient analysis to evaluate floristic compositional changes, phytosociological analysis to evaluate structural variations, and assessed demographic and biomass changes over time through analysis of rates of forest dynamics. The results did not reflect modifications in the patterns of floristic composition and species diversity along the topographic gradient, while differences in forest structural attributes and dynamics may be detected at these smaller spatial scales. Thus, the same species group may employ different strategies against different restrictive environmental factors. Finally, we suggest that floristic composition and species diversity may be less sensitive parameters for post-disturbance responses than forest dynamics and structure

Effect of methylprednisolone on perivascular pulmonary edema, inflammatory infiltrate, VEGF and TGF-beta immunoexpression in the remaining lungs of rats after left pneumonectomy

Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO2/FiO2 ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO2/FiO2 ratio, neutrophil density or TGF-β expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-β expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation