Blebbistatin-Loaded Poly(d,l-lactide-co-glycolide) Particles For Treating Arthrofibrosis.

Joint immobility is a debilitating complication of articular trauma that is characterized by thickening and stiffening of the joint capsule and the formation of fibrotic lesions inside joints. Capsule release surgery can temporarily restore mobility, but contraction often recurs due to the contractile activities of fibroblasts, which exert tension on the capsule ECM via nonmuscle myosin II. Based on these findings we hypothesized that blebbistatin, a drug that reversibly inhibits the activity of this protein, would relax ECM tension imposed by fibroblasts and reduce fibrosis. In this study, we characterized the effectiveness of blebbistatin as an anticontractile treatment. Given that sustained suppression of contractile activity may be required to achieve capsule release and reduce fibrosis, we compared the effects on fibroblast-mediated collagen ECM displacement of blebbistatin-loaded poly(lactide-co-gylcolide) (PLGA) particles versus bolus blebbistatin dosing. Time-lapse imaging of fluorescent microspheres embedded in collagen gels confirmed that PLGA/blebbistatin inhibited force generation and reduced both gel displacement and rate of displacement. In addition, collagen production at 10 days was significantly reduced. Taken together, these data indicate that blebbistatin-loaded PLGA particles can be used to inhibit fibroblast force-generation and reduce collagen production and lay the foundation for optimization of drug delivery technology for treating arthrofibrosis.

In vivo growth inhibition of sarcoma 180 by Kielmeyera rugosa Choisy (Calophyllaceae).

The plant Kielmeyera rugosa Choisy (family Calophyllaceae), popularly known as 'pau-santo', is traditionally used in Brazilian folk medicine. Recently, the dichloromethane extract-dichloromethane partition from stems of K. rugosa (KR) has shown positive results in our cytotoxic screening programme. Therefore, the aim of this study was to validate the antitumour activity of KR on sarcoma 180 tumour-bearing mice. KR showed antitumour activity with both administration routes: intraperitoneal (50 and 100 mg/kg/day) and oral (100 and 200 mg/kg/day). Tumour growth inhibition rates were 40.8-34.9% and 25.4-51.8% after intraperitoneal and oral administrations, respectively. Treatment with KR did not significantly affect body mass, macroscopy of the organs or blood leukocyte counts. In conclusion, KR exhibited an in vivo antitumour effect without substantial toxicity.

How frequently should a patient taking amiodarone be screened for thyroid dysfunction?

Amiodarone-induced thyroid dysfunction (AITD) is a common complication of amiodarone therapy and its prevalence varies according to iodine intake, subclinical thyroid disorders and the definition of AITD. There is no consensus about the frequency of screening for this condition. We evaluated 121 patients on chronic regular intake of amiodarone (mean intake = 248.5 ± 89 mg; duration of treatment = 5.3 ± 3.9 years, range = 0.57-17 years) and with stable baseline cardiac condition. Those with noAITD were followed up for a median period of 3.2 years (range: 0.6-6.7) and the incidence rate of AITD, defined by clinical and laboratorial findings as proposed by international guidelines, was obtained (62.8 per 1000 patients/year). We applied the Coxproportional hazard model to adjust for potential confounding factors and used sensitivity analysis to identify the best screening time for follow-up. We detected thyroid dysfunction in 59 (48.7%) of the 121 patients, amiodarone-induced hypothyroidism in50 (41.3%) and hyperthyroidism in 9 (7.5%). Compared with patients without AITD, there was no difference regarding dosage or duration of therapy, heart rhythm disorder or baseline cardiac condition. During the follow-up of the 62 patients without AITD at baseline evaluation, 11 developed AITD (interquartile range, IR: 62.8 (95%CI: 31.3-112.3) cases per 1000 patients/year), 9 of them with hypothyroidism - IR: 11.4 (95%CI: 1.38-41.2), and 2 hyperthyroidism - IR: 51.3 (95%CI: 23.4-97.5). Age, gender,dose, and duration of treatment were not significant after adjustment. During the first 6 months of follow-up the incidence rate for AITD was 39.3 (9.2-61.9) cases per 1000 patients/year. These data show that AITD is quite common, and support the need for screening at 6-month intervals, unless clinical follow-up dictates otherwise or further information regarding the prognosis of untreated subclinical AITD is available.

Biological behavior of Leishmania amazonensis isolated from humans with cutaneous, mucosal, or visceral leishmaniasis in BALB/C mice.

Leishmania amazonensis causes a wide spectrum of disease in humans. In this study, we evaluated BALB/c mice infected with five strains of L. amazonensis isolated from patients with either cutaneous, mucosal, or visceral leishmaniasis. Mice infected with cutaneous and mucosal isolates developed ulcerating footpad lesions with parasite-loaded macrophages and extensive tissue destruction. Skin metastases, early dissemination of parasites to the spleen, and high anti-Leishmania antibody levels were also noted. Mice infected with L. amazonensis strains isolated from patients with visceral disease had a controlled infection, with small footpad lesions with mononuclear cell infiltration, few infected macrophages, and granuloma formation. They had no skin metastases, delayed dissemination of the parasite to the spleen, lower levels of IgG and higher levels of IgG2a against L. amazonensis. These findings demonstrate an unexpected resistance of BALB/c mice to the infection with L. amazonensis isolated from patients with visceral leishmaniasis. This resistance seems to be due to differences in these parasites that may be related to the altered course of the disease in humans and in isogenic BALB/c mice.

Correlation between cell-mediated immunity and degree of infection in subjects living in an endemic area of schistosomiasis.

Cell-mediated immunity to Schistosoma mansoni antigens, unrelated antigens and mitogens was evaluated in 50 subjects with the same degree of exposure to infection living in an endemic area of schistosomiasis. The degree of infection, assessed by the number of eggs/g of stool, was variable in this population (0-5604), suggesting differences in susceptibility to infection. Absence of lymphoproliferative response was observed in 56% of this group, despite having a response to purified protein derivative of tuberculin (PPD) and tetanus toxoid (TT) antigens and to pokeweed mitogen. The 50 subjects were divided into two groups, according to their degree of infection. The lymphoproliferative responses to schistosomula and adult worm antigens in the group with a low degree of infection (< 400 eggs/g of stool) were higher than the ones documented in patients with a high degree of infection (> 400 eggs/g of stool), and these differences were statistically significant (p < 0.001). An inverse correlation between the lymphocyte proliferation in response to S. mansoni antigens and the degree of infection was also observed (p = 0.02), indicating that subjects with a lower degree of infection have a higher lymphoproliferative response to schistosomula and adult worm antigens. No differences in the lymphocyte reactivity to other antigens (PPD and TT) were detected in these groups. An impairment of interferon-gamma in vitro production was observed when the lymphocytes from these subjects were stimulated with S. mansoni adult worm antigen, although they produced gamma interferon in response to phytohemagglutinin.

A medida da tensao arterial na pratica medica de rotina. / The determination of blood pressure in routine medical practice

Em 11 sevicos medicos da cidade de Salvador (Bahia) foram levantados dados das fichas ou prontuarios dos 1.084 adultos atendidos em primeiras consultas entre zero e 24 horas do dia 20/07/82. Tal levantamento visou analisar as frequencias da medida da tensao arterial ( TA ) na pratica medica de rotina e dos tratamentos efetuados nos casos de hipertensao arterial detectados. A TA foi medicada em l8,7% dos pacientes, sendo que naqueles com idade >/ 35 anos a TA foi medida em 22%. Dos 203 pacientes com TA medida, 22,7% eram hipertensos e 80,4% destes tiveram prescrito ou iniciado o tratamento. Comentou-se a necessidade da melhoria da educacao e resposabilidade medicas, a necessidade da integracao clinico-epidemiologica, alem da participacao ativa da populacao para a detecao precoce da hipertensao arterial, no sentido de minimizar a morbi-mortalidade a ela consequente