Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways.

Skeletal muscle regeneration is ensured by satellite cells (SC), which upon activation undergo self-renewal and myogenesis. The correct sequence of healing events may be offset by inflammatory and/or fibrotic factors able to promote fibrosis and consequent muscle wasting. Angiotensin-II (Ang) is an effector peptide of the renin angiotensin system (RAS), of which the direct role in human SCs (hSCs) is still controversial. Based on the hypertrophic and fibrogenic effects of Ang via transient receptor potential canonical (TRPC) channels in cardiac and renal tissues, we hypothesized a similar axis in hSCs. Toward this aim, we demonstrated that hSCs respond to acute Ang stimulation, dose-dependently enhancing p-mTOR, p-AKT, p-ERK1/2 and p-P38. Additionally, sub-acute Ang conditioning increased cell size and promoted trans-differentiation into myofibroblasts. To provide a mechanistic hypothesis on TRPC channel involvement in the processes, we proved that TRPC channels mediate a basal calcium entry into hSCs that is stimulated by acute Ang and strongly amplified by sub-chronic Ang conditioning. Altogether, these findings demonstrate that Ang induces a fate shift of hSCs into myofibroblasts and provide a basis to support a benefit of RAS and TRPC channel blockade to oppose muscle fibrosis.

Selective Blockade of HCN1/HCN2 Channels as a Potential Pharmacological Strategy Against Pain.

A prominent role of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels has been suggested based on their expression and (dys)function in dorsal root ganglion (DRG) neurons, being likely involved in peripheral nociception. Using HCN blockers as antinociceptive drugs is prevented by the widespread distribution of these channels. However, tissue-specific expression of HCN isoforms varies significantly, HCN1 and HCN2 being considered as major players in DRG excitability. We characterized the pharmacological effect of a novel compound, MEL55A, able to block selectively HCN1/HCN2 isoforms, on DRG neuron excitability in-vitro and for its antiallodynic properties in-vivo. HEK293 cells expressing HCN1, HCN2, or HCN4 isoforms were used to verify drug selectivity. The pharmacological profile of MEL55A was tested on mouse DRG neurons by patch-clamp recordings, and in-vivo in oxaliplatin-induced neuropathy by means of thermal hypersensitivity. Results were compared to the non-isoform-selective drug, ivabradine. MEL55A showed a marked preference toward HCN1 and HCN2 isoforms expressed in HEK293, with respect to HCN4. In cultured DRG, MEL55A reduced I h amplitude, both in basic conditions and after stimulation by forskolin, and cell excitability, its effect being quantitatively similar to that observed with ivabradine. MEL55A was able to relieve chemotherapy-induced neuropathic pain. In conclusion, selective blockade of HCN1/HCN2 channels, over HCN4 isoform, was able to modulate electrophysiological properties of DRG neurons similarly to that reported for classical I h blockers, ivabradine, resulting in a pain-relieving activity. The availability of small molecules with selectivity toward HCN channel isoforms involved in nociception might represent a safe and effective strategy against chronic pain.

Transplante renal em pacientes HIV positivos: relato de dois casos da experiência inicial do Hospital de Clínicas de Porto Alegre / Kidney transplantation in HIV positive patients: two case reports from Hospital de Clínicas de Porto Alegre initial experience

Recentemente, o transplante renal passou a ser uma modalidade terapêutica aceita para o tratamento de pacientes renais crônicos terminais infectados pelo HIV. Para tal, há necessidade de estabilidade de parâmetros clínicos e laboratoriais relacionados à infecção pelo HIV e do uso de terapia antiretroviral de elevada eficiência. Neste relato, apresentamos os dois primeiros casos no Brasil de pacientes portadores de infecção pelo HIV transplantados com órgãos de doadores falecidos realizados com sucesso em nossa instituição. As interações entre os imunossupressores e as drogas antiretrovirais, as coinfecções, o perfil de risco cardiovascular e a elevada incidência de rejeição aguda permanecem os maiores problemas a serem equacionados nestes pacientes.

Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.

[Kidney transplantation in HIV positive patients: two case reports from Hospital de Clínicas de Porto Alegre initial experience]. / Transplante renal em pacientes HIV positivos: relato de dois casos da experiência inicial do Hospital de Clínicas de Porto Alegre.

Recently kidney transplantation has become an accepted treatment modality for the treatment of HIV infected patients with end-stage renal diseases. For such treatment it is required stability of clinical and laboratory parameters related to HIV infection and the use of highly active antiretroviral therapy. In this report we present the first two cases in Brazil of patients with HIV infection transplanted with organs from deceased donors performed successfully in our institution. The interactions between immunosuppressive and antiretroviral drugs, the co-infections, cardiovascular risk profile and the high incidence of acute rejection remain the major problems to be dealt with in these patients.

[Profile of prostate cancer at the general hospital of Porto Alegre]. / Perfil do câncer de próstata no hospital de clínicas de Porto Alegre.

OBJECTIVES: To describe prevalence and features of prostate cancer in the sample. METHODS: A five year long voluntary screening program was carried out in the "Hospital das Clínicas de Porto Alegre" with the participation of 3,056 patients in a cross sectional study. For statistical analysis the chi square test was used, considering a significance level of p < 0.05 RESULTS: Mean age of the sample was of 60.4 years and prevalence of prostate cancer was of 2.61%, increasing with age. Sensitivity and specificity of PSA were respectively 93.8% (CI = 85.4% to 97.7%) and 82.5% (CI = 81.1% to 83.8%), considering 4 ng/ml as the cut-off point for PSA. Rectal examination had a sensitivity of 60% (CI = 48.4% to 70.6%) and a specificity of 83.3% (CI = 81.9% to 84.6%) The number of biopsies performed for the diagnosis of a patient with prostate cancer was 11.9 and varied according to age. As for clinical staging, 51.3% of patients were T1C and 83.75% of the tumors were clinically confined to the organ. CONCLUSION: Screening programs can be performed in our environment and direct to a frequent diagnosis of patients with prostate cancer confined to the organ.

Perfil do câncer de próstata no hospital de clínicas de Porto Alegre / Profile of prostate cancer at the general hospital of Porto Alegre

OBJETIVO: Determinar as características do adenocarcinoma prostático em um programa de rastreamento voluntário realizado no Hospital de Clínicas de Porto Alegre. MÉTODOS: Durante cinco anos consecutivos, 3.056 pacientes foram submetidos a um estudo transversal com o objetivo de determinar a prevalência e características do câncer de próstata na amostra. Foram biopsiados os pacientes com PSA = 4 ng/ml e /ou toque retal alterado. Para a análise estatística foi utilizado o teste qui-quadrado com nível de significância de p < 0,05. RESULTADOS: A prevalência do câncer de próstata foi de 2,61 por cento, sendo crescente com o aumento da idade. A taxa de positividade do PSA apresentou uma sensibilidade e especificidade do PSA foram, respectivamente, 93,8 por cento (IC = 85,4 por cento a 97,7 por cento) e 82,5 por cento (IC = 81,1 por cento a 83,8 por cento), utilizando como ponto de corte do PSA o valor de 4ng/ml. O toque retal apresentou sensibilidade de 60 por cento (IC = 48,4 por cento a 70,6 por cento) e especificidade 83,5 por cento (IC = 81,9 por cento a 84,6 por cento). O número de biópsias realizadas para se diagnosticar um paciente com câncer de próstata foi de 11,9 e variou conforme a faixa etária. No estadiamento clínico, 51,3 por cento dos pacientes eram T1C e 83,75 por cento dos tumores estavam clinicamente confinados ao órgão. CONCLUSAO: Programas de rastreamento de câncer de próstata em nosso meio são exeqüíveis e permitem diagnosticar com freqüência pacientes com neoplasia confinada ao órgão.

[Diagnostic efficiency on digital snapshots of the standard radiology imaging]. / Validità della diagnosi su fotogrammi digitali ottenuti da radiografie convenzionali.

The authors had experienced the telediagnosis on digital snapshots of standard radiology imaging (chest, abdomen, and bones), sent by e-mailing, to support the medical doctors working in remote areas of developing countries. In order to validate the overall procedure, the authors have set up a simulating model and estimated some parameters of accuracy of the diagnosis on digital snapshots against the golden standard of the diagnosis by direct look. The study concerned the standard X-ray tests of one hundred randomly-selected patients out of a hospital archive. Four years later the diagnosis by direct look, the team of radiologists carried out the blind cross check on the digital snapshots of the radiograms and stated their second diagnosis. Sensibility, specificity, predictive value of positives, predictive value of negatives and efficiency of the whole series have been 83.0, 95.1, 96.1, 79.6 and 88.0%. By breaking up the series by apparatus, the skeleton test shows similar data of the whole series. The chest test shows a specificity and predictive value of positives of 100.0%. Although the number of cases is low, the abdomen test apparently shows a sensibility and predictive value of negatives as high as 100%, but a lower specificity and predictive value of negatives (85.7 and 87.5%). Though this data is supportive to the validation of the procedure, even better results are supposedly achieved by increasing the quality of the snapshots and by improving the skills of using the software.

Abscesso esplênico / Splenic abscess

Abscesso esplênico isolado é uma afecção rara, encontrada em 0,14 por cento a 0,7 por cento em séries ne necropsias. A apresentação clínica é inespecífica e o diagnóstico é muitas vezes protelado. Na maioria dos casos o foco hematogênico pode ser identificado. Os autores relatam um raro caso de abscesso esplênico, enfatizando a etiologia, o diagnóstico, terapêutica e evolução.

Isolated splenic abscess is an uncommon condition and are encountered in 0,4% to 0,7% of the autopsy series. The clinical presentation is nonespecific and diagnosis is usually delayed. In most cases an hematogenous focus can be identified. The authors report a case of splenic abscess emphasizing the etiology, diagnosis, treatment and evolution.