Evidence of involvement of the nNOS and the kappa-opioid receptor in the same intracellular network of the rat periaqueductal gray that controls morphine tolerance and dependence

Tolerance and dependence are the most important side effects of opioid-mediated pain therapies. However, the mechanisms through which these phenomena are produced still remain unknown. Among the opioid receptors, the kappa-opioid receptor has been the focus of strong research efforts, since it contributes to the reversal of morphine-induced tolerance and dependence. Parallel to this, neuronal nitric oxide synthase has been shown to play a key role in the development of these unwanted effects. Both the kappa-opioid receptor and neuronal nitric oxide synthase are abundantly located in the CNS. One of the areas where these cellular agents are best represented is a key encephalic nucleus in the development of tolerance to the analgesic action of opioid drugs, the periaqueductal gray. In this work, we studied whether morphine-induced tolerance and dependence causes changes (a) in the activity of neuronal nitric oxide synthase and (b) in kappa-opioid receptor expression in the rat periaqueductal gray. Besides, we examined the colocalization of both molecules. Our results point to an involvement of KOR and nNOS in the same intracellular network that controls the development of morphine tolerance and dependence.     

CT and MR imaging findings of malignant cardiac tumors

This article reviews CT and MRI features of malignant cardiac and pericardial tumors, most of which originate from the lung, breast, melanoma, leukemia, or lymphoma through lymphatic, hematogenous, transvenous, and direct pathways. Although echocardiography establishes the diagnosis in most cases, CT and MRI provide additional physical, spatial, and functional information that further aids the evaluation of metastases. For instance, CT provides superior resolution for detecting calcification or fat, while MRI with its direct multiplanar ability more completely characterizes the heart, pericardium, mediastinum, and lungs. MRI also helps elucidate the pathophysiological effects of these tumors on cardiac function through gated cine-loop sequences. Beyond tumor characterization, both modalities can help confirm diagnosis through the addition of contrast, which helps distinguish tumor from myocardium, thrombus, and blood flow artifact. Ultimately, MRI best facilitates surgical planning and posttreatment follow-up in large part because of its unparalleled ability to locate and delimit these tumors.     

Simultaneous pancreas-kidney transplantation: infectious complications and microbiological aspects

OBJECTIVE: The purpose of this study was to describe the clinical and microbiological characteristics of the infectious complications among simultaneous pancreas-kidney transplantations (SPKT). MATERIALS AND METHODS: Among the first 45 SPKT the mean age was 34 years (range, 21 to 49) and the mean duration of follow-up 13 months (range, 2 to 27 months). RESULTS: Twenty-three patients (51%) presented at least one to three episodes (1.7 mean) of infectious complications that needed hospitalization. The etiology of the infections included 71% bacterial (44% gram-negative rods and 27% gram-positive cocci), 16% viral (12% from CMV and 4% from Herpes sp) and 13% fungal (8% by Candida sp and 4% by others fungus). Wound and urinary infections were most frequent, occurring in 22% and 28% of the patients, respectively. All patients who were submitted to vesical drainage developed infections in contrast a rate of only 44% among patients undergoing enteric drainage. CONCLUSION: Infectious complications are the main cause of morbidity and mortality following simultaneous pancreas-kidney transplantation, especially with vesical drainage. The use of enteric drainage combined with administration of broad spectrum prophylactic antibiotics is recommended.     

Mechanism of the endothelium-dependent vasodilation and the antihypertensive effect of Brazilian red wine

The mechanisms involved in the cardioprotector effect of red wine have not yet been completely elucidated but probably an endothelium-dependent vasodilator action may play a significant role in this effect. Experiments were undertaken to determine whether a Brazilian red wine (BRW) induces vasodilation in the mesenteric vascular bed (MVB) and an antihypertensive effect was also assessed in rats with NO-deficient hypertension. In MVB precontracted with norepinephrine, BRW (alcohol-free lyophilized) induces a long-lasting endothelium-dependent vasodilation that is not reduced by indomethacin. Inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of BRW. In vessels precontracted with norepinephrine and depolarized with KCl (25 Mm) or treated with Ca-dependent K channel blockers charybdotoxin (ChTx) plus apamin, the effect of BRW was significantly reduced. However, this effect is not affected by ATP-dependent K (KATP) channel blocker (glibenclamide). The residual vasodilator effect of BRW observed in vessels pretreated with ChTx plus apamin is completely abolished by ChTx plus apamin plus L-NAME. Concentrations of atropine, pyrilamine, yohimbine, and HOE 140 that significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine, and bradykinin, respectively did not change the vasodilator effect of BRW. Chronic oral administration of BRW induced a significant reduction in systolic, mean and diastolic arterial pressure in rats with L-NAME hypertension. The present results demonstrated that vasodilator effect of BRW is dependent on endothelium-derived hyperpolarizing factor (EDHF) in combination with nitric oxide (NO). The antihypertensive effect of red wine demonstrated in the present study may play a significant role on the cardioprotective action of chronic red wine consumption.     

Value of the Congenital Hypertrophy of the Retinal Pigment Epithelium in the Diagnosis of Familial Adenomatous Polyposis

BACKGROUND: Several kinds of congenital hypertrophy of the retinal pigment epithelium (CHRPE) have been described in patients with familial adenomatous polyposis (FAP). This study aims to assess which properties of CHRPE better predict FAP and investigate whether a relationship exists between specific CHRPE characteristics and FAP variants. METHODS: We examined 286 subjects, Group I--patients with FAP plus individuals "at risk"; n = 173; Group II--controls n = 113. Retinal lesions were classified in five types (A-E) and different characteristics (distribution, number, shape, size, pigmentation and site) were evaluated. RESULTS: The most common lesions in affected subjects were types A-D (83.4%) whilst in the "at risk" and control groups were type E. Greater numbers of lesions and bilateral distribution occurred more frequently among affected subjects than in other participants (p < 0.001). Large lesions with mixed pigmentation were associated with polyposis (p > 0.5). Controls had solitary CHRPE lesions (3.5%) and types C and E lesions (23%). The cumulative sensitivities and specificities of CHRPE were 42 and 97%, respectively. CHRPE was most common among those with classical FAP, but no specific characteristic was associated with any particular FAP variant. CONCLUSIONS: Pigmented fundal lesions are highly pleomorphic and represent the variable expression of a common genetic defect of growth regulation. No association was found between CHRPE characteristics and specific FAP variants.     

Synthesis and evaluation of 9-anilinothiazolo[5,4-b]quinoline derivatives as potential antitumorals

Five new 9-anilinothiazolo[5,4-b]quinoline derivatives (compounds 5, 7, 9, 10, 11) have been prepared. Some of the compounds were prepared by coupling properly substituted anilines to the novel compound 9-chloro-2-(methylthio)thiazolo[5,4-b]quinoline. Of these, compound 7 (9-anilino-2-[[2-(N,N-diethylamino)ethyl]amino]thiazolo[5,4-b]quinoline) showed the best cytotoxic activity in several cell lines. All compounds demonstrated DNA binding in nanomolar range. Compound 7 inhibited the (14)C-thymidine incorporation into DNA. Results indicate that these derivatives deserve more considerations as potential antitumoral drugs.