Spontaneous fertility in a male patient with testotoxicosis despite suppression of FSH levels.

Testotoxicosis is a rare cause of peripheral precocious puberty in boys caused by constitutively activating mutations of the LHCG receptor. Affected males usually have normal gonadotropin profiles and fertility in their adult life. Here, we described the long-term follow-up of a 24-year-old young man with severe testotoxicosis due to a de novo activating mutation in the third transmembrane helix of the LHCGR (p.Leu457Arg). This patient was treated with different medications, including medroxyprogesterone acetate, ketoconazole, cyproterone acetate and aromatase inhibitor from age 2.5 to 9.5 years. His basal and GnRH-stimulated gonadotropin levels were continually suppressed during and after medical treatment. At adulthood, extremely high serum testosterone levels (>35 nmol/L), undetectable gonadotropin levels (LH < 0.15 IU/L and FSH < 0.6 IU/L) and oligozoospermia were evidenced. Despite his suppressed FSH levels and an unfavorable spermogram, the patient fathered a healthy girl and biological paternity was confirmed through analysis of microsatellites. Spontaneous fertility in a young man with severe testotoxicosis and chronic suppression of FSH levels reinforces the key role of high intratesticular testosterone levels in human spermatogenesis.

Effect of AT1 receptor blockade on cardiovascular outcome after cardiac arrest: an experimental study in rats.

Angiotensin II receptor 1(AT1) antagonists are beneficial in focal ischemia/reperfusion (I/R). However, in cases of global I/R, such as cardiac arrest (CA), AT1 blocker's potential benefits are still unknown. Wistar male rats were allocated into four groups: Control group (CG)-animals submitted to CA by ventricular fibrillation induced by direct electrical stimulation for 3 min, and anoxia for 5 min; Group AT1 (GAT1)-animals subjected to CA and treated with 0.2 mg/kg of candesartan diluted in dimethylsulfoxide (DMSO) (0.1%); Vehicle Group (VG): animals subjected to CA and treated with 0.2 ml/kg of DMSO and Sham group (SG)-animals submitted to surgical interventions, without CA. Cardiopulmonary resuscitation consisted of group medications, chest compressions, ventilation, epinephrine (20 mcg/kg) and defibrillation. The animals were observed up to 4 h after spontaneous circulation (ROSC) return, and survival rates, hemodynamic variables, histopathology, and markers of tissue injury were analyzed. GAT1 group had a higher rate of ROSC (62.5% vs. 42.1%, p < 0.0001), survival (100% vs. 62.5%, p = 0.027), lower incidence of arrhythmia after 10 min of ROSC (10% vs. 62.5%, p = 0.000), and lower neuronal and cardiac injury scores on histology evaluation (p = 0.025 and p = 0.0052, respectively) than GC group. The groups did not differ regarding CA duration, number of adrenaline doses, or number of defibrillations. AT1 receptor blockade with candesartan yielded higher rates of ROSC and survival, in addition to neuronal and myocardial protection.

Field study on nematode resistance in Nelore-breed cattle.

The present study evaluated Nelore cattle with different degrees of resistance to natural infections by gastrointestinal nematodes. One hundred weaned male cattle, 11-12 months of age, were kept on the same pasture and evaluated from October 2003 to February 2004. Faecal and blood samples were collected for parasitological, haematological and immunological tests. In February 2004, the 10 most resistant and the 10 most susceptible animals were selected based on individual means of nematode faecal egg counts (FEC). Such animals were slaughtered for worm burden determination and nematode species identification. The repeatability estimates for FEC (+/-S.D.), log-transformed FEC and packed-cell volume (PCV) in all animals were 0.3 (+/-0.05), 0.26 (+/-0.04) and 0.42 (+/-0.05), respectively. The resistant group showed lower FEC and worm burdens than the susceptible group (P<0.05). There were no significant differences between groups regarding mean body weight, weight gain, PCV and total serum protein values (P>0.05). The resistant group showed higher total serum IgE levels (P<0.05) and higher mean eosinophil blood counts. However, the latter was statistically significant only 42 days after the beginning of the study. Nematodes Cooperia punctata and Haemonchus placei were predominant and the correlation between Cooperia and Haemonchus burdens was 0.64 (P<0.05), which indicated that animals presenting increased numbers of one of those genera probably had increased numbers of the other. The current study provides further evidence of IgE active role in nematode immunity and suggests that total serum IgE level might serve as an additional marker to select Nelore cattle that are responsive to H. placei and C. punctata infections.

Evaluation of stallion sperm motility with ImageJ using a cell phone camera and a light microscope / [Avaliação da motilidade espermática de garanhões com ImageJ usando-se câmera de celular e microscópio óptico]

This study aimed to determine the accuracy of assessing stallion sperm motility using a light microscope, a cell phone camera, and a free computer-assisted semen analysis (FCASA) package for ImageJ. The total motility of frozen (n=22) and cooled (n=48) equine semen was determined by FCASA and compared to the results of subjective visual analysis (SVA) by two technicians. Frozen samples were also evaluated by a commercial computer-assisted semen analysis (CCASA) system. The Friedman test revealed no significant differences (P>0.05) between cooled samples analyzed by FCASA (38.0) and SVA (technician 1, 40.0; technician 2, 40.0), nor between frozen samples analyzed by FCASA (23.36 ± 15.9), SVA (25.5 ± 18.8 and 25.8 ± 18.5), and CCASA (25.2 ± 18.3). However, mean FCASA results were underestimated by 7.2% compared with CCASA. The correlation between FCASA and CCASA was significant and strong (P<0.0001, r=0.95). Chi-squared tests indicated that FCASA provided similar results (P=0.14) to the reference method (CCASA), but SVA had lower accuracy (P=0.04). ImageJ analysis of cell phone videos captured under a light microscope can be used for estimation of stallion sperm motility with comparable accuracy to commercial systems.(AU)

O objetivo deste estudo foi testar as configurações necessárias para avaliar a motilidade espermática total de garanhões, mediante o uso de ImageJ, microscópio óptico e câmera de celular. Os valores de motilidade total das amostras de sêmen equino congeladas (22) e refrigeradas (48) foram comparados por análise visual (SVA) e pelo plugin do ImageJ (CASAF). Amostras congeladas também foram comparadas por um CASA comercial (CCASA). O teste de Friedman não resultou em diferença estatística (P>0,05) entre as 48 amostras analisadas com CASAF (38,0) e SVA de dois avaliadores (40,0 e 40,0). A comparação das 22 amostras congeladas entre CASAF (23,36±15,9), SVA (25,5±18,8 e 25,8±18,5) e CCASA (25,2±18,3) também não resultou em diferença estatística, sendo que a média dos resultados obtidos com CASAF subestimou a obtida com o CCASA em 7,2%. A correlação entre CASAF e CCASA foi significativamente elevada (r=0,95, P<0,0001). O teste de qui-quadrado resultou em proporção de acertos semelhantes entre o CASAF e o CCASA (P=0,14), enquanto SVA resultou em proporção diferente (P=0,04), indicando menor acurácia. O uso de microscópio óptico e câmera de celular foi útil para obter vídeos de sêmen de garanhões a serem analisados com ImageJ, proporcionando resultados de motilidade total equiparáveis a sistemas comerciais.(AU)

Variation in population density of horn flies (Haematobia irritans irritans) (L.) (Diptera: Muscidae) in Nellore cattle (Bos indicus).

The population density of horn flies was evaluated in the year 1998 in the municipality of Araçatuba, São Paulo Brazil, in relation to temperature and rainfall conditions. Two lots of 30 Nellore steers (Bos indicus) were used which had no insecticidal treatment and were naturally infested with horn flies. The infestations were assessed by two counting methods, i.e., the traditional estimate method and the filming method. The highest fly frequencies were recorded in spring, summer, autumn and the lowest frequencies were recorded in winter. The increase in fly number was positively correlated (P<0.05) with rainfall.

Comparison of two methods (visual estimates and filming) for counts of horn flies (Haematobia irritans irritans) (L.) (Diptera: Muscidae).

Visual estimates are generally used for counts of horn flies, Haematobia irritans (L.) and play an important role as an instrument to quantify fly populations in scientific studies. In this study, horn fly counts were performed on 30 Nelore steers in the municipality of Araçatuba, SP Brazil, from January to December 1998. Flies were counted weekly by two methods: the estimate method whereby estimates of the number of flies on one side of the animal are obtained by visual observation, and the filming method whereby images of flies from both sides of the animal are recorded with a video camera. The tape was then played on a videotape recorder coupled to a television and the flies were counted on the screen. Both methods showed variations in horn fly population density during the period studied. However, significant differences (p < 0.05) were observed between the two methods with the filming method permitting the visualization of a larger number of flies than the estimate method. In addition, the filming method permitted safe and reliable counts hours after the images were taken, with the advantage that the tape can serve as an archive for random re-counts.

Bovine semen thermoresistance tests and their correlation with pregnancy rates after fixed-time artificial insemination / Testes de termorresistência do sêmen bovino e sua correlação com taxas de prenhez após inseminação artificial em tempo fixo

The objective of the study was to determine whether or not there is a correlation between thermoresistance tests (TT) after semen thawing and pregnancy rate (PR) after fixed-time artificial insemination (FTAI). Four different TT were performed on ten samples used for AI; a rapid test (RTT) (30min / 46°C) and three slow tests (STT): STT1 (60min/38°C), STT2 (180min/38°C), and STT3 (300min/38°C). Two hundred and fifteen multiparous crossbred cows were submitted to FTAI under the following protocol: on day zero (d0) the animals received a P4 device +EB; on d7 PGF2α; on d8 P4 was removed and eCG+EC were administered; IATF was performed on d10. Three gestational diagnoses (G D) were performed on d40, d70 and d120. The mean sperm motility (%) in RTT and STTs were 19.84±6.13, 28.55±10.48, 17.62±5.87 and 8.63±3.46, respectively, and TP in the three DG 61.86%, 57.67%, and 55.81%, respectively. Through Person test a significant negative correlation (P< 0.05) was found between STT2 and PR at 60 days (r= -0.644) and between STT3 and all TPs (r= -0.774, -0.752, 0.748). It was concluded that TT parameters are not able to determine correlation between semen quality and TP.(AU)

O objetivo do presente estudo foi determinar se há ou não correlação entre testes de termorresistência (TT) após descongelamento do sêmen e taxa de prenhez (TP) após inseminação artificial em tempo fixo (IATF). Quatro diferentes TT foram realizados nas 10 amostras utilizadas para a IA; um teste rápido (RTT) (30min/46°C) e três testes lentos (STT): STT1 (60min/38°C), STT2 (180min/38°C) e STT3 (300min/38°C). Duzentas e quinze vacas cruzadas multíparas foram submetidas à IATF sob o seguinte protocolo: no dia zero (d0), os animais receberam um dispositivo de P4+EB; em d7, PGF2α; em d8, retirou-se P4 e eCG+EC administrados; no d10, foi realizada IATF. Três diagnósticos gestacionais (DG) foram feitos, em d40, d70 e d120. As médias de motilidade espermática (%) em RTT e STTs foram 19,84±6,13, 28,55±10,48, 17,62±5,87 e 8,63±3,46, respectivamente, e TP nos três DG 61,86%, 57,67% e 55,81%, respectivamente. Por meio do teste de Person, uma correlação negativa significativa (P<0,05) foi encontrada entre os resultados de STT2 e PR aos 60 dias (r=-0,644) e entre STT3 e todas TPs (r=-0,774, -0,752 e -0,748). Concluiu-se que parâmetros de TT não são capazes de determinar correlação entre qualidade do sêmen e TP.(AU)

Structural basis for the interaction of human ß-defensin 6 and its putative chemokine receptor CCR2 and breast cancer microvesicles.

Human ß-defensins (hBDs) are believed to function as alarm molecules that stimulate the adaptive immune system when a threat is present. In addition to its antimicrobial activity, defensins present other activities such as chemoattraction of a range of different cell types to the sites of inflammation. We have solved the structure of the hBD6 by NMR spectroscopy that contains a conserved ß-defensin domain followed by an extended C-terminus. We use NMR to monitor the interaction of hBD6 with microvesicles shed by breast cancer cell lines and with peptides derived from the extracellular domain of CC chemokine receptor 2 (Nt-CCR2) possessing or not possessing sulfation on Tyr26 and Tyr28. The NMR-derived model of the hBD6/CCR2 complex reveals a contiguous binding surface on hBD6, which comprises amino acid residues of the α-helix and ß2-ß3 loop. The microvesicle binding surface partially overlaps with the chemokine receptor interface. NMR spin relaxation suggests that free hBD6 and the hBD6/CCR2 complex exhibit microsecond-to-millisecond conformational dynamics encompassing the CCR2 binding site, which might facilitate selection of the molecular configuration optimal for binding. These data offer new insights into the structure-function relation of the hBD6-CCR2 interaction, which is a promising target for the design of novel anticancer agents.

Salt and insulin sensitivity after short and prolonged high salt intake in elderly subjects.

Salt sensitivity and insulin resistance are correlated with higher cardiovascular risk. There is no information about changes in salt sensitivity (SS) and insulin sensitivity (IS) after a chronic salt overload in humans. The aim of this study was to evaluate these parameters in the elderly. Seventeen volunteers aged 70.5 +/- 5.9 years followed a low-salt diet (LSD) for 1 week and a high-salt diet (HSD) for 13 weeks. We evaluated SS after one week (HSD1) and after 13 weeks (HSD13), and subjects' IS and lipids on their usual diet (UD) at HSD1, and at HSD13. Blood pressure (BP) was measured at each visit and ambulatory blood pressure monitoring (ABPM) was performed twice. SS was the same at HSD1 and HSD13. Systolic BP was lower on LSD than on UD (P = 0.01), HSD1 (P < 0.01) and HSD13 (P < 0.01). When systolic and diastolic BP were evaluated by ABPM, they were higher at HSD13 during the 24-h period (P = 0.03 and P < 0.01) and during the wakefulness period (P = 0.02 and P < 0.01) compared to the UD. Total cholesterol was higher (P = 0.04) at HSD13 than at HSD1. Glucose and homeostasis model assessment (HOMA) were lower at HSD1 (P = 0.02 and P = 0.01) than at HSD13. Concluding, the extension of HSD did not change the SS in an elderly group. The higher IS found at HSD1 did not persist after a longer HSD. A chronic HSD increased BP as assessed by ABPM.

Procoagulant properties of human MV3 melanoma cells.

A correlation between cancer and prothrombotic states has long been described. More recently, a number of studies have focused on the procoagulant mechanisms exhibited by tumor cells. In the present study, we dissected the molecular mechanisms responsible for the procoagulant activity of MV3, a highly aggressive human melanoma cell line. It was observed that tumor cells strongly accelerate plasma coagulation as a result of: i) expression of the blood clotting initiator protein, a tissue factor, as shown by flow cytometry and functional assays (factor Xa formation in the presence of cells and factor VIIa), and ii) direct activation of prothrombin to thrombin by cells, as evidenced by hydrolysis of the synthetic substrate, S-2238, and the natural substrate, fibrinogen. This ability was highly potentiated by the addition of exogenous factor Va, which functions as a co-factor for the enzyme factor Xa. In contrast, prothrombin activation was not observed when cells were previously incubated with DEGR-factor Xa, an inactive derivative of the enzyme. Moreover, a monoclonal antibody against bovine factor Xa reduced the prothrombin-converting activity of tumor cells. In conclusion, the data strongly suggest that MV3 cells recruit factor Xa from the culture medium, triggering an uncommon procoagulant mechanism.

Controle estatístico de processo univariado: monitoramento da produção de comprimidos de dipirona / Univariate Statistical Process Control: monitoring the production of dipyrone tablets

Investigou-se, através de histogramas e cartas de controle X e S, a ferramenta do Controle Estatístico de Processo (CEP) univariado e os parâmetros físicos dureza, peso médio e friabilidade da produção de dez lotes de dipirona sódica comprimidos. Por sua complexidade e influência no processo, a etapa de granulação de cada lote foi concomitantemente caracterizada através de determinações de densidade bruta, densidade compactada, índice de compressibilidade e fator de Hausner, além dos ângulos de repouso, tempos de escoamento e repartições granulométricas. As caracterizações dos granulados serviram como base na investigação da possível influência da etapa de granulação como uma das prováveis causas que poderiam levar o processo a se apresentar fora de controle estatístico. Os resultados da caracterização indicaram certa uniformidade entre os granulados, o que pode significar que não há ligação aparente entre a etapa de granulação e a falta de controle estatístico do processo, demonstrada na avaliação das cartas de controle. Na medida em que permitiu uma maior compreensão do processo, o CEP univariado mostrou sua importância no monitoramento da produção de comprimidos.

In this study, by means of histograms and and s control charts, the production control tool, univariate Statistical Process Control (SPC), was assessed for monitoring the physical variables hardness, weight and friability during the production of ten batches of sodium dipyrone tablets. In view of its complexity and influence on the process, the granulation step was concurrently characterized by determining the gross density, compacted density, compressibility index and Hausner factor, plus the angle of repose, flow time and particle size distributions of each batch. The properties of the granules were used as a basis for testing the hypothesis that the granulation step is probably the cause when the process runs out of statistical control. The results of the characterization indicated a degree of uniformity among the granules, which may mean that the lack of statistical process control demonstrated in the control charts does not arise from the granulation step. To the extent that it enabled a greater understanding of the process, univariate SCP proved its importance in the monitoring of tablet production.

[Working women and health of 4 groups of women in Guadalajara, Mexico]. / El trabajo femenino y la salud de cuatro grupos de mujeres en Guadalajara, México.

Today, the incorporation of women into the work force has changed the profile of health concerns of this population, extending it beyond the traditional gynecological/obstetrical framework. In order to describe the health problems of women in the context of their activities both inside and outside the home, a descriptive study was carried out using a four-part questionnaire (sociodemographic characteristics, domestic activities, renumerated activities, and the Cornell Medical Index) to identify similarities and differences among nurses, teachers, secretaries, and housewives living in Guadalajara, Mexico, in 1989. The results showed that the working woman's schedule, defined as the time devoted to work both inside and outside the home, is very long in all the groups studied, amounting to a total of between 66 and 78 hours a week. The housewives spend an average of 70 hours a week on domestic tasks, while the nurses, teachers, and secretaries spend between 34 and 42 hours a week on such activities. With regard to work-related risks, occupational diseases were the most common complaint of all the groups, especially the teachers. On the other hand, housewives had the highest overall morbidity according to the Cornell Medical Index. These observations point out that different occupational health risks and morbidity indexes are associated with different activities performed by women, and it is suggested that these differences should be examined more fully through descriptive studies on women's health such as the one presented here.

[Alveolar proteinosis: report of 4 cases]. / Proteinose alveolar: apresentação de quatro casos.

Pulmonary alveolar proteinosis is a rare disease characterized by the filling of the alveolar spaces of the lung by a PAS-positive lipoproteinaceous material. Despite the clear characterization of this material, the etiopathogenesis of the disease remains obscure. We present four patients who were admitted in our Department over the last seven years. The diagnosis was confirmed by lung biopsy in all cases. Three patients improved after bronchoalveolar lavage. Spontaneous remission was observed in one case.

Salt and insulin sensitivity after short and prolonged high salt intake in elderly subjects

Salt sensitivity and insulin resistance are correlated with higher cardiovascular risk. There is no information about changes in salt sensitivity (SS) and insulin sensitivity (IS) after a chronic salt overload in humans. The aim of this study was to evaluate these parameters in the elderly. Seventeen volunteers aged 70.5 ± 5.9 years followed a low-salt diet (LSD) for 1 week and a high-salt diet (HSD) for 13 weeks. We evaluated SS after one week (HSD1) and after 13 weeks (HSD13), and subjects’ IS and lipids on their usual diet (UD) at HSD1, and at HSD13. Blood pressure (BP) was measured at each visit and ambulatory blood pressure monitoring (ABPM) was performed twice. SS was the same at HSD1 and HSD13. Systolic BP was lower on LSD than on UD (P = 0.01), HSD1 (P < 0.01) and HSD13 (P < 0.01). When systolic and diastolic BP were evaluated by ABPM, they were higher at HSD13 during the 24-h period (P = 0.03 and P < 0.01) and during the wakefulness period (P = 0.02 and P < 0.01) compared to the UD. Total cholesterol was higher (P = 0.04) at HSD13 than at HSD1. Glucose and homeostasis model assessment (HOMA) were lower at HSD1 (P = 0.02 and P = 0.01) than at HSD13. Concluding, the extension of HSD did not change the SS in an elderly group. The higher IS found at HSD1 did not persist after a longer HSD. A chronic HSD increased BP as assessed by ABPM.

Procoagulant properties of human MV3 melanoma cells

A correlation between cancer and prothrombotic states has long been described. More recently, a number of studies have focused on the procoagulant mechanisms exhibited by tumor cells. In the present study, we dissected the molecular mechanisms responsible for the procoagulant activity of MV3, a highly aggressive human melanoma cell line. It was observed that tumor cells strongly accelerate plasma coagulation as a result of: i) expression of the blood clotting initiator protein, a tissue factor, as shown by flow cytometry and functional assays (factor Xa formation in the presence of cells and factor VIIa), and ii) direct activation of prothrombin to thrombin by cells, as evidenced by hydrolysis of the synthetic substrate, S-2238, and the natural substrate, fibrinogen. This ability was highly potentiated by the addition of exogenous factor Va, which functions as a co-factor for the enzyme factor Xa. In contrast, prothrombin activation was not observed when cells were previously incubated with DEGR-factor Xa, an inactive derivative of the enzyme. Moreover, a monoclonal antibody against bovine factor Xa reduced the prothrombin-converting activity of tumor cells. In conclusion, the data strongly suggest that MV3 cells recruit factor Xa from the culture medium, triggering an uncommon procoagulant mechanism.

Aplicação do controle estatístico de processo na indústria farmacêutica / The application of statistical process control to the pharmaceutical industry

O controle estatístico de processo (CEP) é uma das mais poderosas metodologias desenvolvidas visando auxiliar no controle eficaz da qualidade. Através das cartas ou gráficos de controle, podem-se detectar desvios de parâmetros representativos do processo, reduzindo a quantidade de produtos fora de especificações e com isso os custos da produção. O controle estatístico de processo embora pouco utilizado na indústria farmacêutica, é uma ferramenta de grande utilidade, pois incorpora também o conceito de boas práticas de fabricação, além de fornecer informações imprescindíveis para a validação de processos, uma vez que permitem a investigação detalhada de todos os pontos críticos de controle, diagnosticando as possíveis não conformidades em todas as etapas do processo, além de sinalizar as possíveis fontes desses desvios de qualidade possibilitando correções e interações com o processo. Apesar de não existir muitas publicações do CEP na indústria farmacêutica, os exemplos de aplicações desta ferramenta provam sua grande importância para a compreensão dos processos que envolvem a obtenção de medicamentos

Métodos de controle da dor pós-operatória / Methods of control of postoperatory pain

A dor pós-operatória é um problema de considerável magnitude e transcendência. Além do sofrimento, ela está geralmente associada a muitos efeitos adversos. Uma melhor compreensäo dos mecanismos neurais envolvidos no processamento da informaçäo nociceptiva e da farmacocinética e farmacodinâmica das drogas usadas em anestesia e controle da dor nos permitiram usar eficazmente métodos farmacológicos e näo farmacológicos para o seu tratamento no pós-operatório. Opióides por via sistêmica, peridural e intratecal; analgesia com quetamina; analgésicos antiinflamatórios näo esteróides; bloqueios neurais; terapia psicológica; eletro-estimulaçäo transcutânea; crioanalgesia e inalaçäo de analgésicos gasosos e voláteis säo discutidos nesta revisäo