Peripheral analgesic activities of peptides related to alpha-melanocyte stimulating hormone and interleukin-1 beta 193-195.

1. The hyperalgesic effects of interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) were measured in rats. 2. Hyperalgesic responses to IL-1 beta were inhibited in a dose-dependent manner by alpha-melanocyte stimulating hormone (alpha-MSH)-related peptides with the following order of potency: [N1(4),D-Phe7]alpha-MSH greater than alpha-MSH greater than Lys-D-Pro-Val greater than Lys-Pro-Val greater than Lys-D-Pro-Thr greater than D-Lys-Pro-Thr. 3. Hyperalgesic responses to PGE2 were not inhibited by Lys-D-Pro-Thr and D-Lys-Pro-Thr but were inhibited in a dose-dependent manner by the other peptides with the same order of potency as against IL-1 beta. 4. The potencies of [N1(4), D-Phe7]alpha-MSH and alpha-MSH were greatly diminished by deletion of their C-terminal tripeptide, Lys11-Pro-Val13. 5. Nor-binaltorphimine (Nor-BNI) largely reversed the analgesic effects of alpha-MSH, [N1(4), D-Phe7]alpha-MSH, Lys-Pro-Val and Lys-D-Pro-Val indicating that kappa-opioid receptors mediated the analgesic activity of these peptides. 6. Nor-BNI did not antagonize the inhibition by Lys-D-Pro-Thr and D-Lys-Pro-Thr of IL-1 beta evoked hyperalgesia indicating that these peptides were not acting via kappa-opioid receptors.     

Histopathological effects of [D-Leu]Microcystin-LR variants on liver, skeletal muscle and intestinal tract of Hypophthalmichthys molitrix (Valenciennes, 1844)

This study evaluated the effects of [D-Leu¹]Microcystin-LR variants, by the exposure of Hypophthalmichthys molitrix to Microcystis aeruginosa NPLJ4. Fish was placed in aquariums and exposed to 10⁵ cells mL⁻¹. For 15 days, 05 individuals were removed every 05 days, and tissue samples of liver, skeletal muscle and intestinal tract were collected for histopathologic analyses. Following exposure, those surviving were placed in clean water for 15 days to evaluate their recovery. A control without toxins was maintained in the same conditions and exhibited normal histology and no tissue damage. In exposed fish, samples were characterized by serious damages that similarly affected the different organs, such as dissociation of cells, necrosis and haemorrhage. Samples showed signs of recovery but severe damages were still observed. The results should be valuable to analyze the potency of microcystin toxicity and to help in the diagnosis of fish deaths.     

Skin cancers and precancerous lesions in Parkinson's disease patients.

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.     

Ultrastructural identification of oligodendrocyte/myelin proteins in corpus callosum of hypothyroid animals

Thyroid hormone (T3) deficiency impairs the development of the CNS, particularly myelination. We have previously described an increase in the frequency of morphological abnormalities in the central myelin sheath in a hypothyroidism model, which reinforced the hypothesis of a role for T3 in myelin compaction. However, there are no data concerning the cellular distribution of myelin proteins in hypothyroid animals. In the present work, we describe the distribution of 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), myelin basic protein (MBP) and proteolipid protein (PLP) throughout the central myelin sheath of a hypothyroidism model. We used euthyroid and hypothyroid adult rats at 90 days of age. In order to induce hypothyroid status, animals received 0.02% methimazol from the 19th gestation day onwards. After perfusion with a fixative mixture, small pieces of corpus callosum were obtained, dehydrated and embedded in LR White resin. Ultrathin sections were immunoreacted, using specific antibodies revealed by a secondary antibody coupled to colloidal gold particles of 10 nm. Gold particle density per region of myelin sheath for each one of these proteins was obtained. In normal animals, CNPase, PLP and MBP were identified in sites that had already been described in previous studies. In hypothyroid animals, CNPase was identified in the region corresponding to compact lamellae, which normally does not contain this protein, while, in this same region, PLP and MBP immunolabeling were decreased. These results suggest that thyroid hormone deficiency impairs the distribution of the major oligodendrocyte/myelin markers. This effect may justify the reduction in myelin sheath compaction previously demonstrated in a similar model of hypothyroidism.     

Is chronic nitrate therapy associated with a different clinical presentation of acute coronary syndrome?

BACKGROUND: Nitrate therapy can induce ischemic preconditioning with a consequent increase in tolerance to ischemia. In the context of acute coronary syndromes (ACS), nitrates may result in a different presentation. with greater protection. OBJECTIVES: To investigate in a population of patients with ACS whether previous chronic use of nitrates results in a different presentation of ACS. METHODS: We studied 287 patients (65 +/- 13 years, 66% male) admitted to our department in the first six months of 2005 with ACS (with and without ST-segment elevation). Of these, 8% were under nitrate therapy at the time of admission. In this group, 27% presented ACS without ST-segment elevation, while in the group without nitrates this value was 58% (p = 0.005). By univariate analysis, the use of nitrates was a predictor of the preferential occurrence of non-ST-segment elevation ACS (OR 0.27, 95% CI 0.10-0.71). After correction for the potential influence of variables (age, gender, previous revascularization and smoking) by multivariate logistic regression, nitrate therapy remained a borderline predictor of clinical presentation as non-ST-segment elevation ACS (OR 0.37, 95% CI 0.13-1.04, p = 0.059). CONCLUSIONS: Previous use of nitrates was associated with a tendency to present as non-ST-segment elevation ACS. This finding may be explained by the hypothesis that nitrates induce pharmacological preconditioning, reducing the transmural extent of myocardial infarction.     

Genomic ancestry of a sample population from the state of São Paulo,Brazil

Allelic frequencies of eight autosomal short‐tandem repeat (STR) loci (TH01, TPOx, CSF1PO, vWA, FES/FPS, F13A1, F13B, and CD4) were determined in 400 individuals born in the State of São Paulo. No significant deviations from Hardy‐Weinberg equilibrium were found in any loci analyzed. The Unweighted Pair‐Group Method with Arithmetic Mean (UPGMA) tree constructed based on genetic distances revealed that the present population was grouped with Europeans, and separated from African and Amerindian populations. Estimates of admixture components based on the gene identity method revealed 79% European, 14% African, and 7% Amerindian contributions to this Brazilian population sample. Am. J. Hum. Biol. 18:702–705, 2006. © 2006 Wiley‐Liss, Inc.     

Superficial femoral artery recanalization with self-expanding nitinol stents: long-term follow-up results.

PURPOSE: Since long-term patency and device integrity of nitinol stents in SFA lesions are not well studied, we examined clinical outcome, patency and device integrity after stenting long lesions using a standardized implantation technique. METHODS: Between 2001 and 2006, 59 patients (74 lesions) were treated with the same nitinol self-expandable stent (Zilver, Cook, USA) and technique for SFA recanalization. Clinical charts and imaging were retrospectively reviewed for patency (primary and assisted-primary), and device integrity. RESULTS: Patients were 74.5 (10.9) years old (range 49 to 93), 64% male, 42% diabetic, 62% hypertensive and 67% current or former smokers. Lesions were 23% TASC B, 16% TASC C, or 61% TASC D. Mean recanalization length was 19 cm (range 3 to 53). Mean number of stents per patient was 2.8 (total 210). Mean follow-up time was 2.4 years (range 3 days to 4.8 years). Kaplan-Meier estimates for primary patency rates were 90%, 78%, 74%, 69%, and 69% at 1, 2, 3, 4 and 4.8 years, respectively. Ten restenoses at a mean of 500 (388) days (1-1251 days) were successfully recanalized. The assisted primary patency rates were 96%, 90%, 90%, 90% and 90% at 1, 2, 3, 4 and 5 years, respectively. Six complete occlusions could not be reverted by a second recanalization procedure, and were treated by surgical bypass (1 case), amputation (3 cases), or medical management (2 cases). One (1.04%) Class II stent fracture was noted. CONCLUSIONS: SFA recanalization with a standardized implantation technique and nitinol stents provides good long-term primary and assisted-primary patency.     

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.