Cell-Cell Interaction-Mediated Signaling in the Testis Induces Reproductive Dysfunction-Lesson from the Toxicant/Pharmaceutical Models.

Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations.

Morphophenotypic Classification of Hepatocellular Carcinoma: the Biliary/Stem Cell Subgroup and Worst Outcome-Implications on Patient Selection.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Current clinical/pathological criteria contribute to risk stratification, but are far from the desired on individualized medicine. Recently, HCC classifications have been published based on immunohistochemical and morphological features. METHODS: A retrospective review of patients submitted to surgical treatment-partial hepatectomy (PH) or liver transplantation (LT), with pathological diagnosis of HCC, in a 9-year period (2007-2015) was performed. RESULTS: Applying the classification of Srivastava et al. (#1), based on the expression of CD31, p53, AFP and CD44, tumour size and presence of vascular invasion, HCC were categorized as low- and high-risk HCC. With the classification of Tsujikawa et al. (#2), HCC were classified into biliary/stem cell marker positive, Wnt signalling positive and the "all negative" HCC, according to the expression of CK19, SALL4, ß-catenin glutamine synthetase, EpCAM and p53. There were sixty-six patients (53 males; 13 females), with median age of 64.5 ± 9.46 years (range 38-86), with solitary HCC, comprehending 37 PH (56.1%) and 29 LT (43.9%). The mean overall survival (OS) was 75.4 ± 6.9 months. Biliary/stem cell type of HCC was a predictive factor of worse OS on the overall population (24.4 versus 78.3 months, p = 0.032) and in PH cohort (11.5 versus 64.01 months, p = 0.016), on uni- and multivariate analyses. CONCLUSION: These results support the relevance of a risk stratification classification of HCC. Classification #2 seems adequate to our reality demonstrating OS impact, allowing its application in future biopsies, prompting individualized medicine.

Uso terapêutico adjuvante de probióticos no efeito tardio da radioterapia pélvica: a retocolite ulcerativa / Therapeutic adjunctive use of probiotics in the late effect of pelvic radiotherapy: ulcerative colitis

A radioterapia pélvica é uma das formas de tratamento para as mulheres acometidas de câncer do colo uterino em todos os estágios. Suas radiações ionizantes agem diretamente no DNA celular, tendo a possibilidade de cura, no caso do câncer cervico uterino. Devido aos efeitos colaterais das radiações, acarreta danos às pacientes, que podem ser crônicos e um deles é a retocolite ulcerativa, uma moléstia que acomete o intestino e o reto. Uma das formas de auxiliar a paciente é o tratamento terapêutico adjuvante com probióticos, que restaura a microbiota intestinal e age como inibidor inflamatório. O objetivo da pesquisa é relatar a importância dos probióticos para que possam ser logo administrados às pacientes.

Macrodactilia na mão: relato de caso / Hand macrodactyly: a case report

Os autores descrevem a evolução de um caso de macrodactilia digital progressiva na mão ao longo de 10 anos e os programas cirúrgicos e de reabilitação utilizados. Criança do sexo feminino foi admitida no Hospital de Reabilitação aos 10 meses de idade, apresentava macrodactilia digital progressiva no II e III quirodáctilos da mão esquerda. Evoluiu com síndrome do túnel do carpo, atrofia e perda da oponência do polegar. Aos dois anos, foi submetida a amputação do III raio; aos seis anos, a encurtamento do II dedo, epifisiodese e, aos nove anos, a retinaculotomia dos flexores, amputação do II raio e restauração da oponência do polegar com a transferência do extensor próprio do índex. Foram necessários vários procedimentos e métodos de tratamento para o alívio dos sintomas de compressão do nervo mediano e resultado final funcional satisfatório. Os autores recomendam a amputação como opção cirúrgica e o tratamento precoce da síndrome do túnel do carpo.

The authors describe the progress over a ten year period of a single hand macrodactyly digital progressive case and corresponding surgical and rehabilitation procedures used. The female child was first evaluated at the hospital at the age of 10 months, with macrodactyly digital progressive at I and II fingers of the left hand. Afterwards she developed carpal tunnel syndrome, atrophy and lost of thumb opposition. The third ray was amputated at age 2. At age 6 she was realized finger shortening, physeal arrest and at age 9 a carpal tunnel release, II ray resection and proprius extensor tendon opponensplasty. Many interventions and treatment methods were required to relieve the compression symptoms of the median nerve and satisfactory final functional result. The authors recommend amputation as a surgical option and early carpal tunnel release.