Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.

Exercícios em cadeia cinética fechada (CCF) são comumente empregados na reabilitação da Síndrome do Impacto do Ombro (SIO), condição dolorosa comum em atletas, relacionada ao desequilíbrio muscular entre os estabilizadores da escápula. O objetivo do estudo foi comparar a atividade eletromiográfica (EMG) do serrátil anterior (SA), trapézio superior (TS), trapézio médio (TM) e trapézio inferior (TI) e a razão EMG destes músculos durante variações do exercício push up em indivíduos assintomáticos e com SIO. Foram avaliados 30 voluntários divididos em dois grupos: controle e SIO. A atividade EMG foi registrada durante a realização do knee push up (KPU) e one-arm knee push up (OKP), em base instável e estável de apoio. Para inferência estatística foi utilizada a análise de variância (ANOVA), pós teste Tukey, com nível de significância de 5%. A superfície instável acarretou diminuição na ativação do SA nos dois grupos e aumento da razão TS/SA (p < .03) no grupo SIO. Os resultados do estudo evidenciaram diferentes respostas de ativação muscular nos indivíduos assintomáticos e com SIO frente a condições que alteram a estabilidade da base de apoio.

Closed Kinetic Chain exercises (CKC) are commonly employed in the rehabilitation of Shoulder Impingement Syndrom (SIS), painful condition common in athletes, related to muscle imbalance between the scapular stabilizers. The objectives of this study was to compare the electromyographic activity (EMG) of the serratus anterior (SA), upper trapezius (UT), middle trapezius (MT) and lower trapezius (LT) and the electromyographic ratio during exercises push up in asyntomatic individuals and SIS. Thirty volunteers divided into two groups: control and SIS. The EMG activity was recorded during the knee push up (KPU) and one-arm knee push up (OKP), on stable and unstable bases of support. For statistical inference was used an analysis of variance (ANOVA) and Tukey post-test, with significance level of 5%. The unstable surface provided in decreased activation of SA in both groups and increased ratios of UT / SA (p < .03) in the SIS. The results of the study showed different responses of muscle activation, in individuals with asymptomatic and SIS, face to conditions that alter the stability of the base of support.

O objetivo do presente estudo foi avaliar os efeitos da fisioterapia convencional e do feedback eletromiográfico (EMG) associados ao treino de tarefas específicas na recuperação da função motora do membro superior de pacientes com hemiparesia em consequência do acidente vascular encefálico. Doze pacientes foram avaliados e divididos de forma aleatória em dois grupos: Grupo 1 - Fisioterapia convencional, Grupo 2 -feedback EMG. Todos os pacientes receberam três sessões semanais de 50 minutos de duração, por oito semanas. Foram avaliados o comprometimento motor, funcionalidade e espasticidade, por meio do teste Fugl-Meyer (FMA), TEMPA e Escala Modificada de Ashworth, respectivamente. Os resultados mostraram que em ambos os grupos não houve alteração da espasticidade e que ocorreu melhora significativa nos valores de FMA, após os programas de reabilitação. Em relação aos escores do TEMPA, somente o grupo 2 apresentou ganhos significativos. A comparação dos ganhos obtidos na escala modificada de Ashworth e FMA não revelou diferenças entre os grupos. No entanto, o grupo 2 apresentou ganhos superiores ao grupo 1 em duas tarefas do teste TEMPA. Os resultados sugerem que o treino funcional utilizando o feedback EMG pode ter efeitos positivos na melhora da função motora do braço, no entanto, devido às pequenas diferenças encontradas entre os grupos, concluiu-se que o feedback EMG não foi superior à outra forma de tratamento.

The purpose of the present study was to evaluate the effects of conventional physical therapy and task specific training associated with electromyographic (EMG) feedback to recover upper limb motor function in patients with hemiparesis caused by stroke. Twelve patients were evaluated and then randomly assigned to either of two groups: Group 1 - Conventional physiotherapy; Group 2 - EMG feedback. Patients attended three weekly 50-min sessions, for eight weeks. The evaluated aspects were motor impairment, motor function, and spasticity, using the Fugl-Meyer Assessment (FMA) test, TEMPA, and the Modified Ashworth Scale (MAS), respectively. Results showed that, in both groups, there were no changes in spasticity in the groups, but there was a significant improvement in FMA values after the rehabilitation programs. Regarding TEMPA scores, only Group 2 presented significant gains. The comparison of the MAS and FMA gains showed no differences between groups. However, group 2 showed greater gains in the two tasks of TEMPA. The results suggest that functional training using EMG feedback can have positive results in improving arm function. However, due to small differences between groups, concluded that EMG/Biofeedback therapy was not superior to other form of treatment.

O objetivo do presente estudo foi analisar o efeito da crioterapia e do aquecimento muscular sobre a flexibilidade dos isquiotibiais associados com 3 minutos de alongamento estático. Para isso, 40 jovens voluntários, de ambos os sexos, foram distribuídos de forma aleatória em quatro grupos: Grupo 1 - Controle, Grupo 2 - Alongamento estático mantido por 3 minutos, Grupo 3 - Alongamento e aquecimento por 20 minutos e Grupo 4 - Alongamento e crioterapia por 20 minutos. Foram realizadas três series de alongamento durante cinco dias consecutivos, sendo realizadas avaliações do ângulo extensor do joelho ao início do protocolo, depois de cada dia e ao final do protocolo. Para a comparação intergrupos foi utilizada a ANOVA com post-hoc Tukey e para a análise intragrupo foi utilizado o teste t pareado, todos com nível de significância de 5%. Os resultados demonstraram que todos os grupos submetidos ao alongamento apresentaram ganho de flexibilidade em relação ao grupo controle. No entanto, não houve diferença estatística entre os grupos submetidos aos diferentes programas de alongamento. Conclui-se que o aumento da flexibilidade se deve ao alongamento e independe da aplicação prévia de hipertermia e/ou hipotermia.

The objective of the present study was to analyze the effect of cryotherapy and muscular warming on the flexibility of the hamstring muscles associated with three minutes of static stretching. Forty young male and female volunteers were randomly included in one of four groups: Group 1 - Control group, Group 2 - Three minutes of static stretching, Group 3 - Stretching preceded by warming using shortwave diathermy (20 minutes), and Group 4 - Stretching preceded by applying cryotherapy (20 minutes) to the posterior thigh region. The program consisted of three series of stretching during five consecutive days and flexibility was assessed by goniometric evaluations of the extensor angle of the knee at the beginning of the protocol, at the end of the day and at the end of the protocol. The intergroup comparison was made through ANOVA post-hoc Tukey and the intragroup by paired t test, all with 5% level of significance. The three experimental groups significantly increased their range of motion in relation to the control group. However, differences were not observed among groups submitted to the different stretching programs. In conclusion, increases in flexibility were due to stretching and did not depend on previous application of hyperthermia and/or hypothermia.

Carboxypeptidase M (CPM) is an extracellular glycosylphosphatidyl-inositol-anchored membrane glycoprotein, which removes the C-terminal basic residues, lysine and arginine, from peptides and proteins at neutral pH. CPM plays an important role in the control of peptide hormones and growth factor activity on the cell surface. The present study was carried out to clone and express human CPM in the yeast Pichia pastoris in order to evaluate the importance of this enzyme in physiological and pathological processes. The cDNA for the enzyme was amplified from total placental RNA by RT-PCR and cloned in the vector pPIC9, which uses the methanol oxidase promoter and drives the expression of high levels of heterologous proteins in P. pastoris. The cpm gene, after cloning and transfection, was integrated into the yeast genome, which produced the active protein. The recombinant protein was secreted into the medium and the enzymatic activity was measured using the fluorescent substrate dansyl-Ala-Arg. The enzyme was purified by a two-step protocol including gel filtration and ion-exchange chromatography, resulting in a 1753-fold purified active protein (16474 RFU mg protein-1 min-1). This purification protocol permitted us to obtain 410 mg of the purified protein per liter of fermentation medium. SDS-PAGE showed that recombinant CPM migrated as a single band with a molecular mass similar to that of native placental enzyme (62 kDa), suggesting that the expression of a glycosylated protein had occurred. These results demonstrate for the first time the establishment of a method using P. pastoris to express human CPM necessary to the development of specific antibodies and antagonists, and the analysis of the involvement of this peptidase in different physiological and pathological processes

Os autores relatam o resultado de um ensaio terapêutico em sagüis com uma cepa de Leishmania donovani isolada de um caso humano fatal de calazar, clinicamente resistente aos antimoniais (Glucantime e Pentostam), Anfotericina B ePentamidina. Os testes cutâneos realizados no paciente para avaliação da imunidade celular foram negativos à exceção do DNCB a 2%. Quatro sangüis adultos (Callithrix jacchus) foram inoculados por via intraperitoneal com uma suspensão deformas amastigotas de L. donovani. Duzentos e dez dias após, todos os animais mostravam formas amastigotas do protozoário, evidenciadas através de punção hepática por aspiração. Iniciou-se então um esquema terapêutico com glucantime (28 mgSb v/kg/dia) em três séries de 10 dias com cinco dias de intervalo entre elas em três dosprimatas,ficando o quarto animal como controle. Nos três animais tratados houve curaparasitológica da doença, o mesmo não ocorrehdo com o controle. O fato de a amostra de L. donovani ter sido, no paciente, resistente aos vários tratamentos e ter sido sensível em modelo experimental à terapêutica com glucantime, sugere a possibilidade de que fatores imunológicos do paciente possam ter contribuído para a evolução fatal da doença.

The authors describe a therapeutic study in marmosets (Callithrix jacchus) of a strain of Leishmania donovani isolated from a fatal human case of Kala-azar. The patient failed to respond to antimoniais (Glucantime and Pentostam), Amphotericin B and pentamidine therapy. Skin tests for the evaluation of cellular immunity were negative with the exception of 2% dinitrochlobenzene. Four adult marmosets were inoculated intraperitoneally with a suspension of amastigotes of L. donovani isolated from the hamster liver and spleen. Two hundred and ten days later all the animals had amastigotes in aspirates obtained by liver puncture. Glucantime treatment 28 mg/kilogram body weightper day for 3 series of 10 days was begun in three animals while the fourth was kept as a control. The three treated animals became parasite free in contrast to the control marmoset. The fact that this strain of L. donovani was unresponsive in the patient, inspite of various attempts at treatment, and yet responded to antimoniais in marmosets suggest that the patients immune response was defective leading to a fatal outcome.