Cytonuclear signaling is essential for long-term alterations of cellular properties. Several pathways involving regulated nuclear accumulation of Ser/Thr kinases have been described but little is known about cytonuclear trafficking of tyrosine kinases. Proline-rich tyrosine kinase 2 (Pyk2) is a cytoplasmic non-receptor tyrosine kinase enriched in neurons and involved in functions ranging from synaptic plasticity to bone resorption, as well as in cancer. We previously showed the Ca 2? -induced, calcineurin-dependent, nuclear localization of Pyk2. Here, we characterize the molecular mechanisms of Pyk2 cytonuclear localization in transfected PC12 cells. The 700-841 linker region of Pyk2 recapitulates its depolarizationinduced nuclear accumulation. This region includes a nuclear export motif regulated by phosphorylation at residue S778, a substrate of cAMP-dependent protein kinase and calcineurin. Nuclear import is controlled by a previously identified sequence in the N-terminal domain and by a novel nuclear targeting signal in the linker region. Regulation of cytonuclear trafficking is independent of Pyk2 activity. The region regulating nuclear localization is absent from the non-neuronal shorter splice isoform of Pyk2. Our results elucidate the mechanisms of Ca 2? -induced nuclear accumulation of Pyk2. They also suggest that Pyk2 nuclear accumulation is a novel type of signaling response that may contribute to specific long-term adaptations in neurons.

BackgroundVitiligo is a chronic disease characterized by the appearance of achromic macules caused by melanocyte destruction. Surgical treatments with melanocyte transplantation can be used for stable vitiligo cases. ObjectivesTo evaluate treatment response to the autologous transplantation of noncultured epidermal cell suspension in patients with stable vitiligo.MethodsCase series study in patients with stable vitiligo submitted to noncultured epidermal cell suspension transplantation and evaluated at least once, between 3 and 6 months after the procedure, to observe repigmentation and possible adverse effects. The maximum follow-up period for some patients was 24 months.ResultsOf the 20 patients who underwent 24 procedures, 25% showed an excellent rate of repigmentation, 50% good repigmentation, 15% regular, and 10% poor response. The best results were observed in face and neck lesions, while the worst in extremity lesions (88% and 33% of satisfactory responses, respectively). Patients with segmental vitiligo had a better response (84%) compared to non-segmental ones (63%). As side effects were observed hyperpigmentation of the treated area and the appearance of Koebner phenomenon in the donor area.Study limitationsSome limitations of the study included the small number of patients, a subjective evaluation, and the lack of long-term follow-up on the results. CONCLUSION: Noncultured epidermal cell suspension transplantation is efficient and well tolerated for stable vitiligo treatment, especially for segmental vitiligo on the face and neck.

Vitamins are organic compounds that play a vital role in the control of metabolic processes. The D complex is considered a nutrient with a hormonal action and has an important participation in the constant maintenance of serum and extracellular calcium levels. The present study aims to analyze the results of 105.588 vitamin D (25(OH)D) measurements obtained from a database from a clinical analysis laboratory in Brazil, between the years of 2011 and 2013. The values of 25(OH)D were correlated with age, gender, and values of PTH. The results show a high prevalence of values of 25(OH)D considered inadequate, characterizing 76% of the studied population. It was observed that 26,5% of the individuals had deficiency and 49,5% had insufficiency of vitamin D. It was also shown that there was a negative correlation between 25(OH)D and PTH levels. In conclusion, this study is in accordance with others that show a high prevalence of vitamin D deficiency in different populations and alerts us for the importance of these measurements and analysis in clinical practice and as a base for diagnosis and treatment of hypovitaminosis.

The aim of this study was to verify the acute effects of the application of local vibration on upper limbs during resistance training on the number of maximum repetitions, metabolic and hormonal responses. 32 volunteers performed a maximum voluntary contraction test during a lat pulldown exercise. After the test, all volunteers underwent one conventional resistance training session and one resistance training session with local vibration. In both interventions, volunteers performed 4 sets with the highest possible number of repetitions of the lat pulldown exercise at 55% of maximum voluntary contraction. During the vibratory resistance training intervention, vibration was locally applied (20-Hz and 12-mm). During the conventional resistance training, volunteers performed the same procedures without vibration. Blood samples were taken at each experimental session before and 5 min after the end of each intervention. No significant differences were observed in number of maximum repetitions between the series of vibratory and conventional training. Serum testosterone, cortisol and lactate were significantly increased after 2 interventions. Vibratory resistance training induced greater increases in testosterone and lactate concentrations. No significant changes were found in creatine kinase, creatinine or urea concentration. These data indicate that local vibration increases the metabolic and anabolic response to the resistance training, without changing the training volume.

Sexually transmitted diseases (STDs) are pathologies that have viruses, bacteria, protozoa and fungi as infectious agents, affecting millions of people worldwide and causing physical and psychological consequences for the carrier. Some of these infections such as HIV, HPV and Chlamydia trachomatis may present an asymptomatic phase, making the diagnosis difficult, which is often only performed when the couple looks for infertility treatment after not achieving spontaneous pregnancy. Infertility affects 15% of couples, 50% of cases are male-related, and it is estimated that STDs, which interfere with the physiology of the male reproductive system and may impair semen in parameters such as motility, concentration, morphology and number, cause 15% of male infertility cases. Since STDs treatments are increasing the expectation and quality of life of infected patients, discussing issues such as sexuality and reproduction is of great importance in clarifying unknown facts. This paper aims to discuss how the infectious processes associated with HIV, HPV and Chlamydia trachomatis can interfere with semen quality causing male infertility without apparent cause.

Swiss mice fed commercial or elemental diets and an oral short-chain fatty acid (SCFA) solution or saline were treated with the cytostatic drug Ara-C (cytarabine, 3.6 mg/mouse/day) for two or four days. Histopathological examination revealed less damage (atrophy, inflammation, or necrosis) to the small intestine and colon caused by Ara-C when SCFA was administered. Accordingly, protein and nucleotide concentrations in the intestinal mucosa were higher in the group receiving SCFA than in the group receiving a placebo of the same pH and osmolarity. Improvement by SCFA treatment was correlated with an increase in the height of the intestinal villi, with no alterations of the crypts. Furthermore, the number of intraepithelial lymphocytes was similar to normal values in animals receiving SCFA and Ara-C. When large doses of SCFA were administered, xanthomized enterocytes appeared, suggesting an accumulation of fatty acids in these cells. We conclude that oral administration of SCFA at close to physiological proportions reduces the inflammation and necrosis caused by Ara-C administration, thus representing a potential factor for the improvement of patients with mucositis caused by cancer treatment.

Background: Apoptosis is an essential form of cell death, the failure of which can lead to cancer development. Cancer including leukemia is usually treated with chemotherapeutic drugs that can be effective, but frequently problems are encountered that impair the success of the treatment. Butyrate is a short-chain fatty acid that can have many effects on different cells, including apoptosis. Methods: The effect of a combination treatment with butyrate and antineoplastic agents Ara-C, etoposide and vincristine is evaluate on the leukemic cell line THP-1. Results: We show that butyrate increased apoptosis induced by the three agents as seen by measurement of DNA content, annexin exposure and morphological characteristics. We also demonstrate that the process of apoptosis induced by butyrate and chemotherapeutic drugs involves the participation of caspases and induced activation of caspase-3, -8 and -9. Conclusions: We believe that butyrate could be a promising therapeutic agent for the treatment of leukemia in combination with other antineoplastic drugs.

Purpose To describe the frequencies of chromosomal abnormalities found in abortion material, and to observe its correlation to maternal age. Methods A retrospective study was conducted based on data obtained from the databank of a medical genetics laboratory in Belo Horizonte, MG, Brazil. A total of 884 results from products of conception analysis were included, 204 of which were analyzed by cytogenetics, and 680 by molecular biology based on quantitative fluorescence polymerase chain reaction (QF-PCR). The frequency of individual chromosomal aberrations and the relationship between the presence of anomalies and maternal age were also evaluated. Results The conventional cytogenetics technique was able to detect 52% of normal and 48% of abnormal results in the analyzed material. Quantitative fluorescence polymerase chain reaction revealed 60% of normal and 40% of abnormal results from the samples evaluated by this method. The presence of trisomy 15 was detected only by cytogenetics, as it was not included in the QF-PCR routine investigation in the laboratory. A significant increase in abnormal results was observed among women aged 35 years or older compared with younger women (p ¼ 0.02). Conclusion Chromosomal aberrations are still a major cause of spontaneous abortion, and the conventional cytogenetics technique is efficient for miscarriage material analysis, but molecular methods such as QF-PCR are adequate complementary strategies to detect the major chromosomal anomalies, leading to technical reports with reliable results.