GABA(B) receptor agonist only reduces ethanol drinking in light-drinking mice

Baclofen, a GABA(B) agonist, reduces ethanol intake in animals and humans, but the contrary or no effect was also reported. Our previous study demonstrated that mice characterized as "loss of control over ethanol intake" had different Gabbr1 and Gabbr2 transcription levels, which express, respectively, the GABA(B1) and GABA(B2) subunits in brain areas related to addictive behavior. In the present study, we tested baclofen on ethanol intake in mice exposed to the free-choice paradigm. Adult male Swiss mice, individually housed, had free access to three bottles: ethanol (5% and 10%) and water. The protocol had four phases: acquisition (AC, 10 weeks), withdrawal (W, 4 cycles during 2 weeks of 2 day-free-choice and 2 day-only-water), reexposure (RE, 2 weeks), and adulteration of ethanol solutions with quinine (AD, 2 weeks). Mice characterized as "loss of control" (A, n = 11, preference for ethanol in AC and maintenance of ethanol intake levels in AD), heavy (H, n = 11, preference for ethanol in AC and reduction of ethanol intake levels in AD), and light (L n = 16, preference for water in all phases) drinkers were randomly distributed into two subgroups receiving either intraperitoneal injections of all doses of baclofen (1.25, 2.5, and 5.0 mg/kg, given each dose twice in consecutive days) or saline, being exposed to free-choice. Fluid consumption was measured 24 h later. Baclofen reduced ethanol intake in group L In group H a reduction compared to AC was observed. Group A maintained their high ethanol intake even after baclofen treatment. Activation of the GABA(B) receptor depends on the precise balance between the GABA(B1) and GABA(B2) subunits, so the disproportionate transcription levels, we reported in group A, could explain this lack of response to baclofen. These data highlight the importance to test baclofen in individuals with different ethanol drinking profiles, including humans. (C) 2012 Elsevier Inc. All rights reserved.

Livros eletrônicos da área médica

O trabalho indica alguns livros eletrônicos gratuitos disponíveis na Internet e destinados à área médica.

Livros on-line da área médica

O trabalho indica alguns sites a serem considerados como alternativa para acesso gratuito a livros on-line disponíveis na Internet e destinados à área médica.

Seeking tools for image fusion between computed tomography, structural and functional magnetic resonance methods for applications in neurosurgery

OBJECTIVE: To evaluate tools for the fusion of images generated by tomography and structural and functional magnetic resonance imaging. METHODS: Magnetic resonance and functional magnetic resonance imaging were performed while a volunteer who had previously undergone cranial tomography performed motor and somatosensory tasks in a 3-Tesla scanner. Image data were analyzed with different programs, and the results were compared. RESULTS: We constructed a flow chart of computational processes that allowed measurement of the spatial congruence between the methods. There was no single computational tool that contained the entire set of functions necessary to achieve the goal. CONCLUSION: The fusion of the images from the three methods proved to be feasible with the use of four free-access software programs (OsiriX, Register, MRIcro and FSL). Our results may serve as a basis for building software that will be useful as a virtual tool prior to neurosurgery.

Influenza dell'Omeostasi Idrico-Elettrolitica sul Ciclo Veglia-Sonno

During the wake sleep (W-S) cycle in mammals, the alternation of the different states, wake, NREM sleep (NREMS) and REM sleep (REMS), is associated not only with electroencephalographic or behavioural changes, but also with modifications in the physiological regulations of the organism. The most evident change is the existence of a suspension of the somatic and autonomic thermoregulatory responses during REMS. Since thermoregulation is prevalently controlled by the Preoptic Area-Anterior Hypothalamus (PO-AH), its suspension during REM sleep has been taken as a sign of an impairment of the hypothalamic integrative activity that could explain the modifications in physiological regulation observed in this sleep stage. The recent finding from our laboratory that the secretion of the antidiuretic hormone arginine-vasopressin (AVP) in response to a central osmotic stimulation is quantitatively the same throughout the different stages of the W-S cycle, has shown that hypothalamic osmoregulation is not suspended during REMS. In order to clarify the extent of the hypothalamic involvement in the regulation of the W-S cycle, we have studied the effects of three days of water deprivation and of two days of recovery during which animals were allowed a free access to water, on the architecture of the W-S cycle. The condition of water deprivation represents a severe challenge involving neuroendocrine and autonomic hypothalamic regulations. In contradiction with thermoregulatory studies, in which it has been clearly demonstrated that a thermal challenge selectively reduces REMS occurrence, the results of this study show that REMS occurrence is mildly reduced only in the third day of water deprivation. The most striking effects produced by water deprivation appear to concern NREMS, which shows a selective and significant reduction in its slow EEG activity (delta-power) but not in its duration. The recovery period is mainly characterized by a disruption of the normal circadian rhythm of REMS occurrence and by a rebound of the delta power in NREMS. Thus, an autonomic challenge different from those related to thermoregulation and an endocrine challenge as the continuous secretion of AVP show to exert different effects on the stages of the wake-sleep cycle. Also, this study demonstrates that the impairment of the hypothalamic integrative activity thought to characterize the occurrence of REMS only involves thermoregulatory structures.

Trochanteric flip osteotomy for cranial extension and muscle protection in acetabular fracture fixation using a Kocher-Langenbeck approach

OBJECTIVE: To describe the advantages and surgical technique of a trochanteric flip osteotomy in combination with a Kocher-Langenbeck approach for the treatment of selected acetabular fractures. DESIGN: Consecutive series, teaching hospital. METHODS: Through mobilization of the vastus lateralis muscle, a slice of the greater trochanter with the attached gluteus medius muscle can be flipped anteriorly. The gluteus minimus muscle can then be easily mobilized, giving free access to the posterosuperior and superior acetabular wall area. Damage to the abductor muscles by vigorous retraction can be avoided, potentially resulting in less ectopic ossification. Ten consecutive cases of acetabular fractures treated with this approach are reported. In eight cases, an anatomic reduction was achieved; in the remaining two cases with severe comminution, the reduction was within one to three millimeters. The trochanteric fragment was fixed with two 3.5-millimeter cortical screws. RESULTS: All osteotomies healed in anatomic position within six to eight weeks postoperatively. Abductor strength was symmetric in eight patients and mildly reduced in two patients. Heterotopic ossification was limited to Brooker classes 1 and 2 without functional impairment at an average follow-up of twenty months. No femoral head necrosis was observed. CONCLUSION: This technique allows better visualization, more accurate reduction, and easier fixation of cranial acetabular fragments. Cranial migration of the greater trochanter after fixation with two screws is unlikely to occur because of the distal pull of the vastus lateralis muscle, balancing the cranial pull of the gluteus medius muscle.

Effect of voluntary exercise on number and volume of cardiomyocytes and their mitochondria in the mouse left ventricle

Voluntary exercise (VE) has a beneficial influence on the heart and mean lifespan. The present study evaluates structural adaptations of cardiomyocytes and their mitochondria due to VE by new, unbiased stereological methods. Female, 7-9-week-old mice were randomly assigned to a control (CG, n = 7) or VE group (EG, n = 7). EG animals were housed in cages with free access to a running wheel and had a mean running distance of 6.7 (1.8) km per day. After 4 weeks, the hearts of all mice were processed for light and electron microscopy. We estimated the number and volume of cardiomyocytes by the disector method and the number and volume of mitochondria by estimation of the Euler number. In comparison to CG, VE did not have an effect on the myocardial volume of the left ventricle (CG: 93 (10), EG: 103 (17) (mm(3))), the number of cardiomyocytes (CG: 2.81 (0.27), EG: 2.82 (0.43) (x10(6))) and their number-weighted mean volume. However, the composition of the cardiomyocytes changed due to VE. The total volume of mitochondria (CG: 21.8 (4.9), EG: 32.2 (4.3) (mm(3)), P < 0.01) and the total number (CG: 3.76 (0.44), EG: 7.02 (1.13) (x10(10)), P < 0.001) were significantly higher in EG than in CG. The mean number-weighted mitochondrial volume was smaller in EG than in CG (P < 0.05). In summary, VE does not alter ventricular volume nor cardiomyocyte volume or number but the oxidative capacity of cardiomyocytes by an increased mitochondrial number and total volume in the left ventricle. These structural changes may participate in the beneficial effects of VE.

Long-term trends of HIV type 1 drug resistance prevalence among antiretroviral treatment-experienced patients in Switzerland

BACKGROUND:Accurate quantification of the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance in patients who are receiving antiretroviral therapy (ART) is difficult, and results from previous studies vary. We attempted to assess the prevalence and dynamics of resistance in a highly representative patient cohort from Switzerland. METHODS:On the basis of genotypic resistance test results and clinical data, we grouped patients according to their risk of harboring resistant viruses. Estimates of resistance prevalence were calculated on the basis of either the proportion of individuals with a virologic failure or confirmed drug resistance (lower estimate) or the frequency-weighted average of risk group-specific probabilities for the presence of drug resistance mutations (upper estimate). RESULTS:Lower and upper estimates of drug resistance prevalence in 8064 ART-exposed patients were 50% and 57% in 1999 and 37% and 45% in 2007, respectively. This decrease was driven by 2 mechanisms: loss to follow-up or death of high-risk patients exposed to mono- or dual-nucleoside reverse-transcriptase inhibitor therapy (lower estimates range from 72% to 75%) and continued enrollment of low-risk patients who were taking combination ART containing boosted protease inhibitors or nonnucleoside reverse-transcriptase inhibitors as first-line therapy (lower estimates range from 7% to 12%). A subset of 4184 participants (52%) had >or= 1 study visit per year during 2002-2007. In this subset, lower and upper estimates increased from 45% to 49% and from 52% to 55%, respectively. Yearly increases in prevalence were becoming smaller in later years. CONCLUSIONS:Contrary to earlier predictions, in situations of free access to drugs, close monitoring, and rapid introduction of new potent therapies, the emergence of drug-resistant viruses can be minimized at the population level. Moreover, this study demonstrates the necessity of interpreting time trends in the context of evolving cohort populations.

Aeromonas salmonicida subsp. salmonicida in the light of its type-three secretion system

Aeromonas salmonicida subsp. salmonicida is an important pathogen in salmonid aquaculture and is responsible for the typical furunculosis. The type-three secretion system (T3SS) is a major virulence system. In this work, we review structure and function of this highly sophisticated nanosyringe in A. salmonicida. Based on the literature as well as personal experimental observations, we document the genetic (re)organization, expression regulation, anatomy, putative functional origin and roles in the infectious process of this T3SS. We propose a model of pathogenesis where A. salmonicida induces a temporary immunosuppression state in fish in order to acquire free access to host tissues. Finally, we highlight putative important therapeutic and vaccine strategies to prevent furunculosis of salmonid fish.

Does nest size matter to laying hens?

Laying hens in loose housing systems have access to group-nests which provide space for several hens at a time to lay their eggs. They are thus rather large and the trend in the industry is to further increase the size of these nests. Though practicality is important for the producer, group-nests should also cater to the egg-laying behaviour of hens to promote good welfare. One of the factors playing a role in the attractiveness of a nest is the amount of enclosure: hens prefer more enclosure when having a choice between different nest types. The aim of this study was to investigate if hens prefer smaller group-nests to lay their eggs given that they may seem more enclosed than larger nests. The relative preference of groups of laying hens for two nest sizes – 0.43m2 vs. 0.86m2 – was tested in a free-access choice test. The experiment was conducted in two consecutive trials with 100 hens each. They were housed from 18 to 36 weeks of age in five groups of 20 animals and had access to two commercial group-nests differing in internal size only. We counted eggs daily as a measure of nest preference. At 28 and 36 weeks of age, videos were taken of the pens and inside the nests on one day during the first 5h of lights-on. The nest videos were used to record the number of hens per nest and their behaviour with a 10min scan sampling interval. The pen videos were observed continuously to count the total number of nest visits per nest and to calculate the duration of nest visits of five focal hens per pen. We found a relative preference for the small nest as more eggs, fewer nest visits per egg and longer nest visit durations were recorded for that nest. In addition, more hens – including more sitting hens – were in the small nests during the main egg-laying period, while the number of standing hens did not differ. These observations indicate that even though both nests may have been explored to a similar extent, the hens preferred the small nest for egg-laying.

La política demográfica del tercer gobierno peronista: justificaciones, repercusiones y resistencias a las restricciones al control de la natalidad (1973-1976)

Desde mediados de la década del '50, el tamaño de la población comenzó a ser considerado en relación a necesidades geopolíticas y proyectos de desarrollo, mientras proliferaban organismos internacionales decididos a influir sobre las conductas reproductivas de los países del Tercer Mundo. En este contexto, Argentina defendió su autonomía e intentó diseñar una política de población que atendiera a su particular situación de caída demográfica. El tercer gobierno peronista incluyó esta problemática en su plan de gobierno y fue más allá de lo discursivo al implementar, por primera vez en el país, medidas coercitivas sobre el libre acceso a la anticoncepción. Estas disposiciones generaron importantes debates sociales que se expresaron en los medios de prensa escrita, al interior de la corporación médica y en las calles, a través del accionar del movimiento feminista y el Frente de Liberación Homosexual. En este artículo nos proponemos iluminar este aspecto poco estudiado por la historiografía, reconstruyendo la cosmovisión de la época sobre el problema demográfico, las contradicciones al interior del gobierno respecto a las medidas a seguir, sus repercusiones y las resistencias que generaron. Consideramos necesario conocer con mayor profundidad este tema y sus perdurables consecuencias negativas en la 'cultura anticonceptiva' del país.

La política demográfica del tercer gobierno peronista: justificaciones, repercusiones y resistencias a las restricciones al control de la natalidad (1973-1976)

Desde mediados de la década del '50, el tamaño de la población comenzó a ser considerado en relación a necesidades geopolíticas y proyectos de desarrollo, mientras proliferaban organismos internacionales decididos a influir sobre las conductas reproductivas de los países del Tercer Mundo. En este contexto, Argentina defendió su autonomía e intentó diseñar una política de población que atendiera a su particular situación de caída demográfica. El tercer gobierno peronista incluyó esta problemática en su plan de gobierno y fue más allá de lo discursivo al implementar, por primera vez en el país, medidas coercitivas sobre el libre acceso a la anticoncepción. Estas disposiciones generaron importantes debates sociales que se expresaron en los medios de prensa escrita, al interior de la corporación médica y en las calles, a través del accionar del movimiento feminista y el Frente de Liberación Homosexual. En este artículo nos proponemos iluminar este aspecto poco estudiado por la historiografía, reconstruyendo la cosmovisión de la época sobre el problema demográfico, las contradicciones al interior del gobierno respecto a las medidas a seguir, sus repercusiones y las resistencias que generaron. Consideramos necesario conocer con mayor profundidad este tema y sus perdurables consecuencias negativas en la 'cultura anticonceptiva' del país.

La política demográfica del tercer gobierno peronista: justificaciones, repercusiones y resistencias a las restricciones al control de la natalidad (1973-1976)

Desde mediados de la década del '50, el tamaño de la población comenzó a ser considerado en relación a necesidades geopolíticas y proyectos de desarrollo, mientras proliferaban organismos internacionales decididos a influir sobre las conductas reproductivas de los países del Tercer Mundo. En este contexto, Argentina defendió su autonomía e intentó diseñar una política de población que atendiera a su particular situación de caída demográfica. El tercer gobierno peronista incluyó esta problemática en su plan de gobierno y fue más allá de lo discursivo al implementar, por primera vez en el país, medidas coercitivas sobre el libre acceso a la anticoncepción. Estas disposiciones generaron importantes debates sociales que se expresaron en los medios de prensa escrita, al interior de la corporación médica y en las calles, a través del accionar del movimiento feminista y el Frente de Liberación Homosexual. En este artículo nos proponemos iluminar este aspecto poco estudiado por la historiografía, reconstruyendo la cosmovisión de la época sobre el problema demográfico, las contradicciones al interior del gobierno respecto a las medidas a seguir, sus repercusiones y las resistencias que generaron. Consideramos necesario conocer con mayor profundidad este tema y sus perdurables consecuencias negativas en la 'cultura anticonceptiva' del país.

開発政策としての優遇アクセスの成果と課題 -- マダガスカルに対する経済制裁を例に

世界貿易機関（WTO）のドーハ開発ラウンドでは、後発開発途上国が無税無枠で他国に輸出できる措置を実施することが協議されているが、ラウンド自体が合意に至っていないため、各国はWTOの枠組みとは別に、二国間で優遇的なアクセスを提供している。本稿では、アメリカおよびEU 市場への優遇アクセスの下で衣料品の輸出を成長させてきたマダガスカルの縫製産業を例に、二国間の優遇アクセスの成果と課題を検討した。マダガスカルでは2009年に政変が発生し、アメリカ政府は同国に対して輸入関税を免除するアフリカ成長機会法（AGOA）の適用を停止した。AGOAの中止は、同国からアメリカ市場向けの輸出を64～78%減少させ、その影響は政変そのものよりも大きいと推定された。また、企業レベルでは、アメリカ向けに輸出していた工場の閉鎖と、それに伴って非熟練労働者を中心に雇用が減少したことが企業データから明らかになった。低所得国に対する優遇アクセスの中止は、輸出額の減少を通じて、教育水準が低い女性の雇用に大きな影響を与える可能性がある。貧困削減の点からは、制度の運用変更が容易な2国間よりも、多国間の枠組みの下で安定的な優遇アクセスが提供されることが望ましい。

Novel application for exergy and thermoeconomic analysis of processes simulated with Aspen Plus

A visual basic application for Microsoft® Excel 2007 has been developed as a helpful tool to perform mass, energy, exergy and thermoeconomic (MHBT) calculations during the systematic analysis of energy processes simulated with Aspen Plus®. The application reads an Excel workbook containing three sheets with the matter, work and heat streams results of an Aspen Plus® simulation. The required information from the Aspen Plus® simulation and the algorithm/calculations of the application are described and applied to an Air Separation Unit (ASU). This application helps the designer when MHBT analyses are performed, as it increases the knowledge of the process simulated with Aspen Plus®. It’s a valuable tool not only because of the calculations performed, but also because it creates a new Excel workbook where the results and the formulae written on the cells are fully visible and editable. There is free access to the application and it has no protection allowing changes and improvements to be done.