Vector incrimination and effects of antimalarial drugs on malaria transmission and control in the Amazon Basin of Brazil

World ecosystems differ significantly and a multidisciplinary malaria control approach must be adjusted to meet these requirements. These include a comprehensive understanding of the malaria vectors, their behavior, seasonal distribution and abundance, susceptibility to insecticides (physiological and behavioral), methods to reduce the numbers of human gametocyte carriers through effective health care systems and antimalarial drug treatment, urban malaria transmission versus rural or forest malaria transmission, and the impact of vaccine development. Many malaria vectors are members of species complexes and individual relationship to malaria transmission, seasonal distribution, bitting behavior, etc. is poorly understood. Additionaly, malaria patients are not examined for circulating gametocytes and both falciparum and vivax malaria patients may be highly infective to mosquitoes after treatment with currently used antimalarial drugs. Studies on the physiological and behavioral effects of DDT and other insecticides are inconclusive and need to be evalusted.

Effects of antibacterial agents and drugs monitored by atomic force microscopy.

Originally invented for topographic imaging, atomic force microscopy (AFM) has evolved into a multifunctional biological toolkit, enabling to measure structural and functional details of cells and molecules. Its versatility and the large scope of information it can yield make it an invaluable tool in any biologically oriented laboratory, where researchers need to perform characterizations of living samples as well as single molecules in quasi-physiological conditions and with nanoscale resolution. In the last 20 years, AFM has revolutionized the characterization of microbial cells by allowing a better understanding of their cell wall and of the mechanism of action of drugs and by becoming itself a powerful diagnostic tool to study bacteria. Indeed, AFM is much more than a high-resolution microscopy technique. It can reconstruct force maps that can be used to explore the nanomechanical properties of microorganisms and probe at the same time the morphological and mechanical modifications induced by external stimuli. Furthermore it can be used to map chemical species or specific receptors with nanometric resolution directly on the membranes of living organisms. In summary, AFM offers new capabilities and a more in-depth insight in the structure and mechanics of biological specimens with an unrivaled spatial and force resolution. Its application to the study of bacteria is extremely significant since it has already delivered important information on the metabolism of these small microorganisms and, through new and exciting technical developments, will shed more light on the real-time interaction of antimicrobial agents and bacteria.

Efeitos da ingestão de cafeína Em exercício aeróbio de alta intensidade em hipóxia : parâmetros fisiológicos e perceptuais = Effects of caffeine ingestion on high-intensity aerobic exercise in hypoxia : physiological and perceptual parameters

Universidade Estadual de Campinas . Faculdade de Educação Física

EFFECTS OF 14-WEEK SWIMMING TRAINING PROGRAM ON THE PSYCHOLOGICAL, HORMONAL, AND PHYSIOLOGICAL PARAMETERS OF ELITE WOMEN ATHLETES

Santhiago, V, da Silva, ASR, Papoti, M, and Gobatto, CA. Effects of 14-week swimming training program on the psychological, hormonal, and physiological parameters of elite women athletes. J Strength Cond Res 25(3): 825-832, 2011-The purpose of the study was to investigate the influence of a 14-week swimming training program on psychological, hormonal, and performance parameters of elite women swimmers. Ten Olympic and international-level elite women swimmers were evaluated 4 times along the experiment (i.e., in T1, T2, T3, and T4). On the first day at 8: 00 AM, before the blood collecting at rest for the determination of hormonal parameters, the athletes had their psychological parameters assessed by the profile of mood-state questionnaire. At 3: 00 AM, the swimmers had their anaerobic threshold assessed. On the second day at 3: 00 AM, the athletes had their alactic anaerobic performance measured. Vigor score and testosterone levels were lower (p <= 0.05) in T4 compared with T3. In addition, the rate between the peak blood lactate concentration and the median velocity obtained in the alactic anaerobic performance test increased in T4 compared with T3 (p < 0.05). For practical applications, the swimming coaches should not use a tapering with the present characteristics to avoid unexpected results.

Rebound acid hypersecretion after withdrawal of gastric acid suppressing drugs: new evidence of similitude

Background: Homeopathy is based on the principle of similitude (similia similibus curentur) using medicines that cause effects similar to the symptoms of disease in order to stimulate the reaction of the organism. Such vital, homeostatic or paradoxical reaction of the organism is closely related to rebound effect of drugs. Method: Review of the literature concerning the rebound effects of drugs used to suppress gastric acidity, particularly proton pump inhibitors (PPIs). Results: The mechanism of action of these effects is discussed. Rebound in terms of clinical symptoms and physiological effects occur in about 40% of people taking PPIs, their timing depends on the half-life of the drug and the adaptation period of the physiological mechanisms involved. The wide use of PPIs may be linked to the rising incidence of carcinoid tumours. Conclusions: These findings support Hahnemann`s concept of secondary action of drugs. We are developing a homeopathic materia medica and repertory of modern drugs on the basis of reported rebound effects. Homeopathy (2011) 100, 148-156.

An evaluation of the genotoxic and cytotoxic effects of the anti-obesity drugs sibutramine and fenproporex

Anti-obesity medications deserve special considerations at the present time due to an increasing number of overweight and obese people who require these therapeutic alternatives. Obesity is positively associated with several chronic illnesses, including cancer. In this work, we evaluated the possible genotoxic and/or cytotoxic actions of two drugs, sibutramine and fenproporex, in the doses of 10, 20 and 40 mg/kg body weight (bw), administered intraperitoneally in male Swiss mice. The genotoxic effect was analyzed by comet assay and micronucleus test. We found that both drugs increased the frequency of genotoxic damage in Swiss mice, but did not present cytotoxic activities towards the polychromatic erythrocytes of the bone marrow of these animals.

Effects of the length and timing of nighttime naps on task performance and physiological function

OBJECTIVE: To examine the effects of the length and timing of nighttime naps on performance and physiological functions, an experimental study was carried out under simulated night shift schedules. METHODS: Six students were recruited for this study that was composed of 5 experiments. Each experiment involved 3 consecutive days with one night shift (22:00-8:00) followed by daytime sleep and night sleep. The experiments had 5 conditions in which the length and timing of naps were manipulated: 0:00-1:00 (E60), 0:00-2:00 (E120), 4:00-5:00 (L60), 4:00-6:00 (L120), and no nap (No-nap). During the night shifts, participants underwent performance tests. A questionnaire on subjective fatigue and a critical flicker fusion frequency test were administered after the performance tests. Heart rate variability and rectal temperature were recorded continuously during the experiments. Polysomnography was also recorded during the nap. RESULTS: Sleep latency was shorter and sleep efficiency was higher in the nap in L60 and L120 than that in E60 and E120. Slow wave sleep in the naps in E120 and L120 was longer than that in E60 and L60. The mean reaction time in L60 became longer after the nap, and faster in E60 and E120. Earlier naps serve to counteract the decrement in performance and physiological functions during night shifts. Performance was somewhat improved by taking a 2-hour nap later in the shift, but deteriorated after a one-hour nap. CONCLUSIONS: Naps in the latter half of the night shift were superior to earlier naps in terms of sleep quality. However performance declined after a 1-hour nap taken later in the night shift due to sleep inertia. This study suggests that appropriate timing of a short nap must be carefully considered, such as a 60-min nap during the night shift.

Effects of antihypertensive drugs in the differentiation and activation of human bone cells

O osso é um tecido metabolicamente ativo e a sua remodelação é importante para regular e manter a massa óssea. Esse processo envolve a reabsorção do material ósseo por ação dos osteoclastos e a síntese de novo material ósseo mediado pelos osteoblastos. Vários estudos têm sugerido que a pressão arterial elevada está associada a alterações no metabolismo do cálcio, o que leva ao aumento da perda de cálcio e da remoção de cálcio do osso. Embora as alterações no metabolismo ósseo sejam um efeito adverso associado a alguns fármacos antihipertensores, o conhecimento em relação a este efeito terapêutico ligado com os bloqueadores de canais de cálcio é ainda muito escasso. Uma vez que os possíveis efeitos no osso podem ser atribuídos à ação antihipertensiva dessas moléculas, ou através de um efeito direto nas atividades metabólicas ósseas, torna-se necessário esclarecer este assunto. Devido ao facto de que as alterações no metabolismo ósseo são um efeito adverso associado a alguns fármacos antihipertensores, o objetivo deste trabalho é avaliar o efeito que os bloqueadores dos canais de cálcio exercem sobre as células ósseas humanas, nomeadamente osteoclastos, osteoblastos e co-culturas de ambos os tipos celulares. Verificou-se que os efeitos dos fármacos antihipertensores variaram consoante o fármaco testado e o sistema de cultura usado. Alguns fármacos revelaram a capacidade de estimular a osteoclastogénese e a osteoblastogénese em concentrações baixas. Independentemente da identidade do fármaco, concentrações elevadas revelaram ser prejudiciais para a resposta das células ósseas. Os mecanismos intracelulares através dos quais os efeitos foram exercidos foram igualmente afetados de forma diferencial pelos diferentes fármacos. Em resumo, este trabalho demonstrou que os bloqueadores dos canais de cálcio utilizados possuem a capacidade de afetar direta- e indiretamente a resposta de células ósseas humanas, cultivadas isoladamente ou co-cultivadas. Este tipo de informação é crucial para compreender e prevenir os potenciais efeitos destes fármacos no tecido ósseo, e também para adequar e eventualmente melhorar a terapêutica antihipertensora de cada paciente.

Characterization of the effects of antiepileptic drugs on bone metabolism: in vitro studies with human osteoblastic and osteoclastic cells

Bone is constantly being molded and shaped by the action of osteoclasts and osteoblasts. A proper equilibrium between both cell types metabolic activities is required to ensure an adequate skeletal tissue structure, and it involves resorption of old bone and formation of new bone tissue. It is reported that treatment with antiepileptic drugs (AEDs) can elicit alterations in skeletal structure, in particular in bone mineral density. Nevertheless, the knowledge regarding the effects of AEDs on bone cells are still scarce. In this context, the aim of this study was to investigate the effects of five different AEDs on human osteoclastic, osteoblastic and co-cultured cells. Osteoclastic cell cultures were established from precursor cells isolated from human peripheral blood and were characterized for tartrate-resistant acid phosphatase (TRAP) activity, number of TRAP+ multinucleated cells, presence of cells with actin rings and expressing vitronectin and calcitonin receptors and apoptosis rate. Also, the involvement of several signaling pathways on the cellular response was addressed. Osteoblastic cell cultures were obtained from femur heads of patients (25-45 years old) undergoing orthopaedic surgery procedures and were then studied for cellular proliferation/viability, ALP activity, histochemical staining of ALP and apoptosis rate. Also the expression of osteoblast-related genes and the involvement of some osteoblastogenesis-related signalling pathways on cellular response were addressed. For co-cultured cells, osteoblastic cells were firstly seeded and cultured. After that, PBMC were added to the osteoblastic cells and co-cultures were evaluated using the same osteoclast and osteoblast parameters mentioned above for the corresponding isolated cell. Cell-cultures were maintained in the absence (control) or in the presence of different AEDs (carbamazepine, gabapentin, lamotrigine, topiramate and valproic acid). All the tested drugs were able to affect osteoclastic and osteoblastic cells development, although with different profiles on their osteoclastogenic and osteoblastogenic modulation properties. Globally, the tendency was to inhibit the process. Furthermore, the signaling pathways involved in the process also seemed to be differently affected by the AEDs, suggesting that the different drugs may affect osteoclastogenesis and/or osteoblastogenesis through different mechanisms. In conclusion, the present study showed that the different AEDs had the ability to directly and indirectly modulate bone cells differentiation, shedding new light towards a better understanding of how these drugs can affect bone tissue.

Schistosoma mansoni: effects of anesthetics and antimonial drugs on worm shift in the mouse

Mice experimentally infected with Schistosoma mansoni were injected with sodium thiopental or sodium antimonyl gluconate (Triostib R), or submitted to halothane inhalation, with or without a previous injection of thiopental. Data obtained showed that halothane and thiopental induce worm shift to the liver (99 and 76%, respectively). Sodium gluconate and antimonium (Triostib R) shifted 52% of worms towards the liver. These results seem to indicate that the use of antimonium would be unnecessary, when surgical removal of schistosomules is carried out through the extracorporeal filtration technique, in patients with portal hypertension.

A study of the endocervical columnar cells II - effects of physiological changes and of oathological lesions of the uterus on the specific numerical composition of the endocervical epithelium

In the second part of this paper we nalysed the correlation between the clinical pathological alterations and the sum of the types of columnar cells of 300 histological sections of cervix. Fifty histological sections of normal cervix of sexually mature women were selected and considered as normal in pattern. The specific counts of the columnar cells which line the endocervical mucosa and those of the glands of 50 normal cervices were compared with other similar counts made in 50 histological sections of cervices of old women and emphasized the differences. Comparisons were made also between 50 normal cervices and 50 sections of cervices with chronic inflammation, 50 cervices with epidermoid metaplasia and 50 cervices with myoma of the corpus. Counts were made from 50 cervices of patients who on the occasion of the surgical operation were in the proliferative phase of the menstrual cycle; these were compared with the counts of 50 cervices of uteri in the luteal phase. Finally, the numerical frequency of the following data encountered in the 300 cervices was recorded: 1. aspects of the ectocervical epithelium; 2. number of Nabothian cysts; 3. number of cervical glands; 5. number of deliveries and 6. aspect of the material within the cervical canal.

Effects of physiological self-crowding of DNA on shape and biological properties of DNA molecules with various levels of supercoiling.

DNA in bacterial chromosomes and bacterial plasmids is supercoiled. DNA supercoiling is essential for DNA replication and gene regulation. However, the density of supercoiling in vivo is circa twice smaller than in deproteinized DNA molecules isolated from bacteria. What are then the specific advantages of reduced supercoiling density that is maintained in vivo? Using Brownian dynamics simulations and atomic force microscopy we show here that thanks to physiological DNA-DNA crowding DNA molecules with reduced supercoiling density are still sufficiently supercoiled to stimulate interaction between cis-regulatory elements. On the other hand, weak supercoiling permits DNA molecules to modulate their overall shape in response to physiological changes in DNA crowding. This plasticity of DNA shapes may have regulatory role and be important for the postreplicative spontaneous segregation of bacterial chromosomes.

Effects of immunosuppressive drugs on T helper cells subsets and potential to promote tolerance in a stringent experimental transplantation model.

To achieve the goal of sustained donor-specifi c transplantation (Tx) tolerance, research efforts are now focusing on therapies based on specifi c cell subsets with regulatory properties. We and others have previously highlighted the therapeutic potential of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTreg) in promoting long-term graft acceptance. Using more stringent experimental Tx models, we were however confronted to limitations. Indeed, while the transfer of antigenspecifi c nTreg promoted long-term MHC-mismatched skin allograft acceptance in lymphopenic mice in the absence of any immunosuppressive drug, allograft survival was only slightly prolonged when nTreg were transferred alone into non-lymphopenic mice. This suggested that in more stringent conditions, adjuvant therapies may be needed to effectively control alloreactive T cells (Teff). Whether and how the expansion of the Treg pool could be best combined with current immunosuppressive regimens in clinical settings remains to be defi ned. In this study, we have used in vitro assays and an in vivo skin Tx model to investigate the effects of various immunosuppressive drugs on the survival, proliferation and effector function of Teff and nTreg in response to alloantigens. Teff proliferation was inhibited in a dose-dependent manner by rapamycin and cyclosporine A, while anti-CD154 mAb only marginally affected Teff survival, proliferation and effector fucntion in vitro. Rapamycin promoted apoptosis of Teff as compared to nTreg that were more resistant in the presence of IL-2. In vivo, the transfer and/or expansion of Treg could be advantageously combined with rapamycin and anti-CD154 mAb treatment to signifi cantly prolong MHC-mismatched skin allografts survival in non-lymphopenic recipients. Taken together our data indicate that immunosuppressive drugs differentially target T-cell subsets and that some regimens could promote Treg expansion while controlling the Teff pool in response to alloantigens.