Advances in the crosstalk between maternal separation and voluntary ethanol consumption and effects on reproduction.

Maternal separation (SM) is an event caused by early stress and may be associated with behavioral changes and vulnerabilities, enhancing ethanol consumption in adulthood. The aim of the study was to evaluate whether MS potentiates the effects of ethanol ingestion on physiological hormone regulation and its interference in testicular and epididymal morphofunctional aspects in voluntary ethanol-consuming rats. Therefore, for the first time, we investigated the effect of maternal separation and ethanol consumption in adulthood and for this we used free choice ethanol-consuming strains. Responses of metabolic and hormonal parameters were also addressed, as well as their effects on reproductive function. In summary, MS promoted an increase in voluntary ethanol consumption in UChA and UChB animals. There was an influence of MS on the increase of circulating corticosterone and testosterone in UChB animals (high-ethanol-preferring 10 % v/v). MS performed in the hyporesponsive period to stress promoted an increase in glucose and circulating lipids, as well as a reduction in lactate dehydrogenase levels. Daily sperm production and transit time through the epididymis in UChB animals were increased by MS. Together, these findings show that MS potentiates the effects of ethanol ingestion and promotes an imbalance in plasma hormone concentrations, interfering with the reproductive functional imbalance of ethanol-consuming rats.

Strength training protects against prostate injury in alcoholic rats.

Alcoholic injury can alter the hormonal signaling pathway and lead to glucose and lipid metabolism disorders. In this study, we investigated whether the strength training could exert protective effects against the alterations caused by ethanol consumption on prostatic metabolism. A UChB, ethanol-preferring rats were used in this study. Strength training was conducted for 3 days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a strength training protocol. The reduced alcohol consumption by strength training was accompanied by increased glucose, serum lipid profile, total protein levels, and reduced hormonal levels. The results of protein expression of prostatic tissues in the ethanol- and strength training-treated groups indicated that "steroidal hormone receptors," "fatty acid translocation," and "cell regulation" were significantly different between ethanol- and strength training-treated groups. Taken together, these findings show that strength training effectively ameliorated prostatic injuries in alcoholic rats at least partially by acting on lipids receptors and steroidal hormone receptors pathway, suggesting the strength training as a potential novel therapeutic strategy for treating prostate injuries caused by ethanol.

Increased toll-like receptors and p53 levels regulate apoptosis and angiogenesis in non-muscle invasive bladder cancer: mechanism of action of P-MAPA biological response modifier.

BACKGROUND: The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network). This study detailed and characterized the mechanisms of action of P-MAPA based on activation of mediators of Toll-like Receptors (TLRs) 2 and 4 signaling pathways and p53 in regulating angiogenesis and apoptosis in an animal model of NMIBC, as well as, compared these mechanisms with BCG treatment. RESULTS: Our results demonstrated the activation of the immune system by BCG (MyD88-dependent pathway) resulted in increased inflammatory cytokines. However, P-MAPA intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway (TRIF-dependent pathway), which was more effective in the NMIBC treatment. Interferon signaling pathway activation induced by P-MAPA led to increase of iNOS protein levels, resulting in apoptosis and histopathological recovery. Additionally, P-MAPA immunotherapy increased wild-type p53 protein levels. The increased wild-type p53 protein levels were fundamental to NO-induced apoptosis and the up-regulation of BAX. Furthermore, interferon signaling pathway induction and increased p53 protein levels by P-MAPA led to important antitumor effects, not only suppressing abnormal cell proliferation, but also by preventing continuous expansion of tumor mass through suppression of angiogenesis, which was characterized by decreased VEGF and increased endostatin protein levels. CONCLUSIONS: Thus, P-MAPA immunotherapy could be considered an important therapeutic strategy for NMIBC, as well as, opens a new perspective for treatment of patients that are refractory or resistant to BCG intravesical therapy.

Chronic ethanol consumption alters all-trans-retinoic acid concentration and expression of their receptors on the prostate: a possible link between alcoholism and prostate damage.

BACKGROUND: Ethanol (EtOH) alters the all-trans-retinoic acid (ATRA) levels in some tissues. Retinol and ATRA are essential for cell proliferation, differentiation, and maintenance of prostate homeostasis. It has been suggested that disturbances in retinol/ATRA concentration as well as in the expression of retinoic acid receptors (RARs) contribute to benign prostate hyperplasia and prostate cancer. This study aimed to evaluate whether EtOH consumption is able to alter retinol and ATRA levels in the plasma and prostate tissue as well as the expression of RARs, cell proliferation, and apoptosis index. METHODS: All animals were divided into 4 groups (n = 10/group). UChA: rats fed 10% (v/v) EtOH ad libitum; UChACo: EtOH-naïve rats without access to EtOH; UChB: rats fed 10% (v/v) EtOH ad libitum; UChBCo: EtOH-naïve rats without access to EtOH. Animals were euthanized by decapitation after 60 days of EtOH consumption for high-performance liquid chromatography and light microscopy analysis. RESULTS: EtOH reduced plasma retinol concentration in both UChA and UChB groups, while the retinol concentration was not significantly different in prostate tissue. Conversely, plasma and prostate ATRA levels increased in UChB group compared with controls, beyond the up-regulation of RARß and -γ in dorsal prostate lobe. Additionally, no alteration was found in cell proliferation and apoptosis index involving dorsal and lateral prostate lobe. CONCLUSIONS: We conclude that EtOH alters the plasma retinol concentrations proportionally to the amount of EtOH consumed. Moreover, high EtOH consumption increases the concentration of ATRA in plasma/prostate tissue and especially induces the RARß and RARγ in the dorsal prostate lobe. EtOH consumption and increased ATRA levels were not associated with cell proliferation and apoptosis in the prostate.

The expression of aquaporins 1 and 9 in adult rat epididymis is perturbed by chronic exposure to ethanol.

Aquaporins (AQPs), notably AQP-1 and AQP-9, may contribute to reabsorption of fluid and solute across the epididymis. Ethanol is related to be a toxicant affecting directly or indirectly the epididymis and the sperm motility. This study examined the expression of AQP-1 and AQP-9 in adult epididymis of the UChA and UChB 10% (v/v) ethanol-preferring rats, focusing the ethanol-induced hormonal disturbances upon the regulation of these AQPs. Chronic ethanol intake significantly decreased body weight, while UChA and UChB rats displayed a marked loss of epididymal weights. Both ethanol-consuming animals had a severe reduction of testosterone levels, whereas LH and 17ß-estradiol were unchanged. Throughout the epididymis, a strong reaction to AQP-1 was observed in myoid and endothelial cells of the UChB ethanol-preferring rats, differently from a moderate intensity in the initial segment of the UChA rats. In addition, AQP-9 showed a strong immunoreaction in the apical membrane of principal cells at initial segment. In cauda epididymis, the level of AQP-9 was reduced along the microvillus projections in both UChA and UChB rats compared to controls. We conclude that chronic ethanol consumption modulates the androgen levels, thereby modifying the expression pattern of AQP-1 and 9 in the epididymis.

Long-term exogenous melatonin treatment modulates overall feed efficiency and protects ovarian tissue against injuries caused by ethanol-induced oxidative stress in adult UChB rats.

BACKGROUND: Chronic ethanol intake leads to reproductive damage including reactive oxygen species formation, which accelerates the oxidative process. Melatonin is known to regulate the reproductive cycle, food/liquid intake, and it may also act as a potent antioxidant indoleamine. The aim of this study was to verify the effects of alcoholism and melatonin treatment on overall feed efficiency and to analyze its protective role against the oxidative stress in the ovarian tissue of UChB rats (submitted to 10% [v/v] voluntary ethanol consumption). METHODS: Forty adult female rats (n = 10/group) were finally selected for this study: UChB Co: drinking water only; and UChB EtOH: drinking ethanol at 2 to 6 ml/100 g/d + water, both receiving 0.9% NaCl + 95% ethanol 0.04 ml as vehicle. Concomitantly, UChB Co + M and UChB EtOH + M groups were infused with vehicle + melatonin (100 µg/100 g body weight/d) intraperitoneally over 60 days. All animals were euthanized by decapitation during the morning estrus (4 am). RESULTS: Body weight gain was reduced with ethanol plus melatonin after 40 days of treatment. In both melatonin-treated groups, it was observed a reduction in food-derived calories and liquid intake toward the end of treatment. The amount of consumed ethanol dropped during the treatment. Estrous cycle was longer in rats that received both ethanol and melatonin, with prolonged diestrus. Following to oxidative status, lipid hydroperoxide levels were higher in the ovaries of ethanol-preferring rats and decreased after melatonin treatment. Additionally, antioxidant activities of superoxide dismutase, glutathione peroxidase activity, and glutathione reductase activity were increased in melatonin-treated groups. CONCLUSIONS: We suggest that melatonin is able to affect feed efficiency and, conversely, it protects the ovaries against the oxidative stress arising from ethanol consumption.

COMPLICATIONS FOLLOWING MEDIAL OPENING WEDGE OSTEOTOMY OF THE KNEE: RETROSPECTIVE STUDY.

OBJECTIVE: To retrospectively survey the most frequent complications from medial opening wedge high-tibial osteotomy. This procedure is becoming increasingly important in treating knee arthrosis, as one of the options for young and active patients. Despite satisfactory results and its benefits, it is not a complication-free procedure. METHODS: All cases of medial opening wedge high-tibial osteotomy above the tibial tubercle with fixation using a Puddu plate that were performed at the Celso Pierro Hospital and Maternity Hospital, Pontifical Catholic University of Campinas (PUC-Campinas) and the Wilson Mello Institute, Campinas, between October 1, 1987, and October 30, 2008, were evaluated retrospectively. Patients with less than 12 months of follow-up or incomplete medical files, and those who underwent bilateral osteotomy, were excluded. RESULTS: Out of the 67 cases evaluated, 55 were males and 12 were females, with a mean age of 49.5 years. The mean wedge size was 10.15 mm and the most common complications were moderate to severe pain (13.04%), stiffness (6.52%), material breakage (4.4%), intraoperative fracture of the lateral cortical bone (4.4%) and infection (4.4%). It was observed that patients with delayed consolidation of the osteotomy had a greater chance of presenting complications (p < 0.05). CONCLUSION: Complications from medial wedge osteotomy are more frequent when associated with delayed consolidation.

Complicações da osteotomia em cunha de abertura medial do joelho: estudo retrospectivo / Complications following medial opening wedge osteotomy of the knee: retrospective study

OBJETIVO: Realizar um levantamento retrospectivo das complicações mais frequentes da osteotomia tibial alta (OTA) em cunha de abertura medial. Esse procedimento vem a cada vez ganhando mais espaço no tratamento da artrose do joelho como uma das opções para pacientes jovens e ativos. Apesar dos resultados satisfatórios e seus benefícios, não é procedimento isento de complicações. MÉTODOS: Foram avaliados, retrospectivamente, todos os pacientes submetidos à OTA supratuberositária medial de cunha de abertura e fixados com placa do tipo Puddu, realizadas no período de 1 de outubro de 1987 a 30 de outubro de 2008, no Hospital e Maternidade Celso Pierro da Pontifícia Universidade Católica de Campinas (PUC-Campinas) e no Instituto Wilson Mello em Campinas. Foram excluídos pacientes com menos de 12 meses de seguimento, com prontuários incompletos, e os que tinham osteotomias bilaterais. RESULTADOS: Dos 67 casos avaliados, 55 eram do sexo masculino e 12 do feminino, com média de idade de 49,5 anos. O tamanho médio da cunha foi de 10,15mm e as complicações mais frequentes foram dor moderada e grave (13,04 por cento), seguida de rigidez (6,52 por cento), quebra de material (4,4 por cento), fratura da cortical lateral intraoperatória (4,4 por cento) e infecção (4,4 por cento). CONCLUSÃO: Foi observado aumento de probabilidade de complicações quando há retardo na consolidação da osteotomia (p < 0,05). Foi possível concluir que as complicações da osteotomia de cunha medial são mais frequentes quando há associação de retardo de consolidação.

OBJECTIVE: To retrospectively survey the most frequent complications from medial opening wedge high-tibial osteotomy. This procedure is becoming increasingly important in treating knee arthrosis, as one of the options for young and active patients. Despite satisfactory results and its benefits, it is not a complication -free procedure. METHODS: All cases of medial opening wedge high-tibial osteotomy above the tibial tubercle with fixation using a Puddu plate that were performed at the Celso Pierro Hospital and Maternity Hospital, Pontifical Catholic University of Campinas (PUC -Campinas) and the Wilson Mello Institute, Campinas, between October 1, 1987, and October 30, 2008, were evaluated retrospectively. Patients with less than 12 months of follow-up or incomplete medical files, and those who underwent bilateral osteotomy, were excluded. RESULTS: Out of the 67 cases evaluated, 55 were males and 12 were females, with a mean age of 49.5 years. The mean wedge size was 10.15 mm and the most common complications were moderate to severe pain (13.04 percent), stiffness (6.52 percent), material breakage (4.4 percent), intraoperative fracture of the lateral cortical bone (4.4 percent) and infection (4.4 percent). It was observed that patients with delayed consolidation of the osteotomy had a greater chance of presenting complications (p < 0.05) . CONCLUSION: Complications from medial wedge osteotomy are more frequent when associated with delayed consolidation.

Confiabilidade e validade de um dinamômetro isométrico modificado na avaliação do desempenho muscular em indivíduos com reconstrução do ligamento cruzado anterior / Reliability and validity of a modified isometric dynamometer in the assessment of muscular performance in individuals with anterior cruciate ligament reconstruction

OBJETIVO: Analisar a confiabilidade e validade de um dinamômetro isométrico modificado (DIM) na avaliação dos déficits no desempenho muscular dos extensores e flexores do joelho em indivíduos normais e com reconstrução do LCA. MÉTODOS: Foram convidados 60 voluntários do sexo masculino a participar do estudo, divididos em três grupos de 20 indivíduos: grupo controle (GC), grupo com reconstrução do LCA com tendão patelar (GTP) e grupo com reconstrução do LCA com tendões flexores (GTF). Todos os indivíduos realizaram teste isométrico dos extensores e flexores do joelho no DIM; os déficits de força muscular coletados foram comparados posteriormente com os testes realizados no Biodex System 3 operando no modo isométrico e isocinético nas velocidades de 60º/s e 180º /s. Foram realizados cálculos de correlação intraclasse ICC para avaliar a confiabilidade do DIM, cálculos da especificidade, sensibilidade e coeficiente de concordância Kappa, respectivamente, para avaliar a validade do DIM em detectar déficits musculares e comparações intragrupos e intergrupos na realização dos quatro testes de força utilizando-se do método ANOVA. RESULTADOS: O DIM demonstrou excelente confiabilidade teste-reteste e validade na avaliação do desempenho muscular dos extensores e flexores do joelho. Na comparação intergrupos. o GTP demonstrou déficits significativamente maiores dos extensores comparados com os grupos GC e GTF. CONCLUSÃO: Dinamômetros isométricos conectados em equipamentos de mecanoterapia podem ser uma alternativa para coletar dados referentes a déficits no desempenho muscular dos extensores e flexores do joelho em indivíduos com reconstrução do LCA.

OBJECTIVES: The aim of this study was to evaluate the reliability and validity of a modified isometric dynamometer (MID) in performance deficits of the knee extensor and flexor muscles in normal individuals and in those with ACL reconstructions. METHODS: Sixty male subjects were invited to participate of the study, being divided into three groups with 20 subjects each: control group (GC), group of individuals with ACL reconstruction with patellar tendon graft (GTP, and group of individuals with ACL reconstruction with hamstrings graft (GTF). All individuals performed isometric tests in the MID, muscular strength deficits collected were subsequently compared to the tests performed on the Biodex System 3 operating in the isometric and isokinetic mode at speeds of 60º/s and 180o/s. Intraclass ICC correlation calculations were done in order to assess MID reliability, specificity, sensitivity and Kappa's consistency coefficient calculations, respectively, for assessing the MID's validity in detecting muscular deficits and intra-and intergroup comparisons when performing the four strength tests using the ANOVA method. RESULTS: The modified isometric dynamometer (MID) showed excellent reliability and good validity in the assessment of the performance of the knee extensor and flexor muscles groups. In the comparison between groups, the GTP showed significantly greater deficits as compared to the GTF and GC groups. CONCLUSION: Isometric dynamometers connected to mechanotherapy equipments could be an alternative option to collect data concerning performance deficits of the extensor and flexor muscles groups of the knee in subjects with ACL reconstruction.

Análise da correlação entre pico de torque, desempenho funcional e frouxidão ligamentar em indivíduos normais e com reconstrução do ligamento cruzado anterior / Functional performance and knee laxity in normal individuals and in individuals submitted to anterior cruciate ligament reconstruction

Objetivo: Analisar a correlação entre os déficits musculares dos extensores e flexores do joelho através do pico de torque isocinético com os testes de salto monopodal, frouxidão ligamentar pós-operatória e questionário de função em indivíduos normais e indivíduos submetidos à reconstrução do LCA com enxerto autólogo do tendão patelar e dos tendões flexores. Métodos: Foramrecrutados 60 indivíduos, formando três grupos: 20 indivíduos sem lesões no joelho (grupo GC) e dois grupos de 20 indivíduos submetidos à reconstrução do LCA com tendão patelar (grupo GTP) ou tendões flexores (grupo GTF). Resultados: Os resultados demonstraram correlação significativa entre déficits no pico de torque e testes funcionais no torque extensor nos grupos GTF e GC. Não foram observadas correlações significativas entre frouxidão ligamentar pós-operatória e questionário de Lysholm com os testes de salto e déficits no pico de torque. Em relação à diferença entre os grupos, foi observado que o grupo GTP demonstroumaior déficit do torque extensor, menor pontuação no questionário de Lysholm e maior percentagem dos indivíduos com índice de simetria entre membros (ISM) < 90% em ambos os testes de saltomonopodal quando comparado com os demais grupos. Conclusão: Na avaliação funcional de pacientes submetidos à reconstrução do LCA, não é aconselhável a utilização de apenas um instrumento de medida, porque a correlação significativa entre déficit no pico de torque, questionários de função, frouxidão ligamentar e testes de salto não é encontrada em todos os grupos testados.

Objectives: The aim of this study was to analyze the correlation between deficits in the isokinetic peak torque of the knee extensors and flexors with hop tests, postoperative knee laxity and functional scores in normal and ACL- reconstructed subjects with patellar tendon and hamstring tendon autografts. Methods:Sixty male subjects were enrolled and subdivided into three groups: Twenty subjects without knee injuries (GC group) and two groups of 20 subjects submitted to ACL reconstruction withpatellar tendon (GTP group) and hamstrings autograft (GTF group). Results: The results showed significant correlation between knee extensors peak torque and performance in the hoptests for GTF and GC groups. There are no significantly correlations between post op knee laxity and Lysholm score compared with the hop tests and peak torque deficits. Concerning the differences between groups, the GTP group showed greater peak torque deficits in knee extensors, worst Lysholm scores and higher percentage of individuals with lower limb symmetryindex (ISM) < 90% in both hop tests when compared to the other two groups. Conclusion: It is not recommendable to use only one measurement instrument for the functional evaluation of ACL-reconstructed patients, because significant correlation between peak torque, subject's functional score, knee laxity and hop tests were not observed in all groups.

FUNCTIONAL PERFORMANCE AND KNEE LAXITY IN NORMAL INDIVIDUALS AND IN INDIVIDUALS SUBMITTED TO ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.

UNLABELLED: The aim of this study was to analyze the correlation between deficits in the isokinetic peak torque of the knee extensors and flexors with hop tests, postoperative knee laxity and functional scores in normal and ACL- reconstructed subjects with patellar tendon and hamstring tendon autografts. METHODS: Sixty male subjects were enrolled and subdivided into three groups: Twenty subjects without knee injuries (GC group) and two groups of 20 subjects submitted to ACL reconstruction with patellar tendon (GTP group) and hamstrings autograft (GTF group). RESULTS: The results showed significant correlation between knee extensors peak torque and performance in the hop tests for GTF and GC groups. There are no significantly correlations between post op knee laxity and Lysholm score compared with the hop tests and peak torque deficits. Concerning the differences between groups, the GTP group showed greater peak torque deficits in knee extensors, worst Lysholm scores and higher percentage of individuals with lower limb symmetry index (ISM) < 90% in both hop tests when compared to the other two groups. CONCLUSION: It is not recommendable to use only one measurement instrument for the functional evaluation of ACL-reconstructed patients, because significant correlation between peak torque, subject's functional score, knee laxity and hop tests were not observed in all groups.

Anatomia, histologia e ultra-estrutura do lobo ventral da próstata de ratos (Rattus norvegicus) vasectomizados / Anatomy, histology and ultrastructure of prostate ventral lobe of vasectomized (Rattus norvegicus)

A vasectomia é um método de contracepçäo amplamente utilizado, que tem sido associado ao carcinoma da próstata em estudos epidemiológicos. Contudo, poucos estudos morfológicos foram realizados sobre a possibilidade da vasectomia alterar a estrutura da próstata. Este trabalho apresenta uma revisäo de literatura que associa a vasectomia ao câncer da próstata, bem como resultados de estudo experimental em ratos. Dividiu-se um total de 48 ratos machos albinos (Rattus norvegicus), com 6 a 8 semanas de idade, em dois grupos : simulado e vasectomizado. Perfundiu-se, com glutaraldeído a 2,5 por cento, seis ratos de cada grupo após 60, 120, 180 e 360 dias pós-vasectomia. Coletou-se o lobo ventral da próstata para análise microscópica. No estudo ao microscópio de luz, näo se observaram diferenças estruturais entre os grupos estudados. Em ambos grupos näo se encontraram evidências de carcinoma da próstata. A análise morfométrica da altura do epitélio prostático näo demonstrou diferença significativa entre vasectomizados e simulados. Ultra-estruturalmente, as células epiteliais do grupo simulado apresentaram núcleo basal com contorno irregular, retículo endoplasmático rugoso amplamente distribuído, complexo de Golgi bem desenvolvidos, grânulos de secreçäo em diferentes graus de maturidade no citoplasma apical, e microvilos na superfície luminal. Detectou-se características similares nas células prostáticas dos animais vasectomizados, porém, nos períodos iniciais pós-cirurgia, o citoplasma apical continha menor quantidade de grânulos de secreçäo. Os resultados permitem sugerir que a secreçäo prostática diminui logo após a vasectomia, voltando à normalidade posteriormente. Nos ratos vasectomizados, as células epiteliais do lobo ventral da próstata näo demonstraram quaisquer sinais de degeneraçäo ou de carcinoma como efeito da vasectomia.