Cannabinoid receptor type 1 activation by arachidonylcyclopropylamide in rat aortic rings causes vasorelaxation involving calcium-activated potassium channel subunit alpha-1 and calcium channel, voltage-dependent, L type, alpha 1C subunit.

Cannabinoids are key regulators of vascular tone, some of the mechanisms involved include the activation of cannabinoid receptor types 1 and 2 (CB); the transient receptor potential cation channel, subfamily V, member 1 (TRPV1); and non-(CB(1))/non-CB2 receptors. Here, we used the potent, selective CB(1) agonist arachidonylcyclopropylamide (ACPA) to elucidate the mechanism underlying vascular tone regulation. Immunohistochemistry and confocal microscopy revealed that CB(1) was expressed in smooth muscle and endothelial cells in rat aorta. We performed isometric tension recordings in aortic rings that had been pre-contracted with phenylephrine. In these conditions, ACPA caused vasorelaxation in an endothelium-independent manner. To confirm that the effect of ACPA was mediated by CB(1) receptor, we repeated the experiment after blocking these receptors with a selective antagonist, AM281. In these conditions, ACPA did not cause vasorelaxation. We explored the role of K(+) channels in the effect of ACPA by applying high-K(+) solution to induce contraction in aortic rings. In these conditions, the ACPA-induced vasorelaxation was about half that observed with phenylephrine-induced contraction. Thus, K(+) channels were involved in the ACPA effect. Furthermore, the vasorelaxation effect was similarly reduced when we specifically blocked calcium-activated potassium channel subunit alpha-1 (KCa1.1) (MaxiK; BKCa) prior to adding ACPA. Finally, ACPA-induced vasorelaxation was also diminished when we specifically blocked the calcium channel, voltage-dependent, L type, alpha 1C subunit (Ca(v)1.2). These results showed that ACPA activation of CB(1) in smooth muscle caused vasorelaxation of aortic rings through a mechanism involving the activation of K(Ca)1.1 and the inhibition of Ca(v)1.2.

Effects of chronic caffeine administration on blood glucose levels and on glucose tolerance in healthy and diabetic rats.

OBJECTIVE: To analyse the effect of chronic caffeine use on risk reduction and prognosis of diabetes mellitus. METHODS: In this 60-day study, five groups of 11 healthy male Wistar rats were selected to receive one of four doses (37.5, 56.2, 75.0 or 93.0 mg/kg per day) of caffeine orally or no caffeine (control). The effect of caffeine on glycaemia and glucose tolerance was evaluated. After 15 days, each group was treated with 60 mg/kg of streptozotocine to induce diabetes mellitus, and glycaemia and glucose tolerance were assessed for a further 45 days. RESULTS: In nondiabetic rats, caffeine had no effect on blood glucose. Compared with controls, the fasting blood glucose levels declined significantly in two caffeine-treated groups (93.0 mg/kg per day and 56.2 mg/kg per day) during the first 15 days following diabetes induction. Glucose tolerance was significantly improved 120 min after glucose loading in all caffeine-treated groups. The mean ± SE half-maximal effective concentration of caffeine was 35.79 ± 2.44 mg/dl. CONCLUSIONS: Blood glucose levels decreased, and glucose tolerance improved, in diabetic rats administered increasing doses of caffeine.

[Gastrointestinal damage in osteoarthritis patients]. / Lesão gastroduodenal assintomática em portadores de osteoartrose.

Seventy-seven patients with symptomatic osteoarthritis of the hip and/or knee, with clinical indication for nonsteroidal anti-inflammatory drugs were studied. However, no patient was submitted to any anti-inflammatory medication seven days, prior the beginning of the study and did not complain of any gastrointestinal disease. Shortly before starting the anti-inflammatory drug therapy all patients were submitted to gastroduodenal endoscopy. This diagnostic procedure revealed that 54.6% of the patients presented at least one gastroduodenal damage, 22.1%, hyperemia, 3.9%, petechias, 23.4%, erosions and 5.2%, peptic ulcers. There results permitted to conclude that to identify and/or exclude damage of the gastrointestinal tract, data obtained in the anamnese are not sufficient. For these patients the endoscopic examination is a need. Anti-inflammatory therapy must be careful associated with dietetic orientation and the prescription of drugs to protect the gastrointestinal mucosa.

Cardiac and skeletal muscle scintigraphy in dermato- and polymyositis: clinical implications.

To determine the role of scintigraphy in the detection of skeletal and cardiac involvement in dermato- and polymyositis (DM/PM), we studied 30 patients with a confirmed diagnosis of DM/PM (23 females, 7 males; mean age: 35 years). Technetium-99m pyrophosphate (99mTc-PYP) and gallium-67 scans showed similar sensitivity, specificity and accuracy in the detection of skeletal muscle involvement when compared with serum enzymes (70%, 100% and 80%, respectively). Compared with the clinical parameters, 99mTc-PYP showed 70% and 67Ga 65% accuracy. Abnormal PYP cardiac uptake was observed in 57% of patients, whereas abnormal 67Ga cardiac uptake was seen in only 15%. Electrocardiography was abnormal in 40%, rest gated blood pool study in 23%, and chest X-ray in 13%. In conclusion, both 99mTc-PYP and 67Ga can be useful in the detection of the active phase of muscle disease. However, 99mTc-PYP seems to be more effective than 67Ga in the early diagnosis of cardiac involvement.

[Non steroidal anti-inflammatory drugs and rheumatic diseases]. / Antiinflamatórios não esteróides e doenças reumatológicas.

Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

[Radiological staging index of osteoarthrosis]. / Indice de estadiamento radiológico na osteoarthrose.

The association of joint pain with radiological changes (such as osteophytes, joint space narrowing, and sometimes, bone cysts and erosion) is the most commonly criteria used in daily medical practice for the diagnosis of osteoarthrosis. However, these findings do not allow objective quantification of the intensity of the joint involvement. In an attempt to measure quantitatively the radiological lesions encountered in osteoarthrosis the authors elaborated a radiological index based on the following parameters: I. severity of radiological changes, II. area of the affected joint and III. number of affected joints. The application of this index in the medical practice allows a simple way of quantification of radiological lesions of osteoarthrosis and thus, a better clinical monitorization of the disease.

[Minipulses of cyclophosphamide in the treatment of dermatopolymyositis with lung involvement]. / Mini-pulsos de ciclofosfamida no tratamento da dermatopolimiosite com envolvimento pulmonar.

A new scheme for the treatment of dermatopolymyositis with pulmonary fibrosis not responding to corticosteroid therapy is presented. Monthly endovenous administration of a small dose of cyclophosphamide is advocated. Two patients with dermatopolymyositis not responding to prednisone were treated for two years with small doses of cyclophosphamide given monthly after which recovered from muscular and pulmonary involvement showing at present normal clinical parameters.

[Physiatric treatment of pain in osteoarthrosis]. / Tratamento fisiátrico da dor na osteoartrose.

The osteoarthrosis is a disease of high incidence in the population affecting chiefly middle-aged women. The chronic pain is the main cause of incapacity and may be responsible for the secondary articular alterations in theses patients. This paper reviews the physiopathology and the treatment of the pain in osteoarthrosis.

Vasculite urticariforme.Relato de caso e revisao de literatura. / Urticarial vasculitis. A case report and review of the literature

Relatamos o caso do paciente do sexo masculino, de 27 anos, com urticaria cronica como manifestacao de vasculite necrosante cutanea, associada a artrite, febre, emagrecimento e hipocomplementemia. A sindrome caracterizada neste paciente e semelhante aos casos previamente relatados como "vasculite hipocomplementemica", "vasculite necrosante associada a urticaria cronica" e "vasculite urticariforme". Apresentamos revisao de literatura e discussao do diagnostico diferencial e tratamento. Acreditamos que essa nova sindrome constitui uma subpopulacao distinta de patologia colageno-vascular