Synthetic derivatives of curcumin and their activity against Leishmania amazonensis

In a previous work, the in vitro and in vivo activity of a series of diarylheptanoid derivatives against Leishmania amazonensis has been described. Based on the promising results, ten new compounds belonging to the same chemical class were synthesized and have been investigated in relation to their leishmanicidal activity. The compounds were obtained through several chemical modifications on the basic structure of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in an attempt to increase its effectiveness and decrease the potential toxic effects. The drugs were assayed in vitro against L. amazonensis promastigotes and using pentamidine isethionate as reference drug. The results showed that the most effective compound is 1,7-bis-(4-propargyl-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, which is about ten times more efficient than the original curcumin. Nevertheless, these results did not allow us to make any correlation between the leishmanicidal activity and the chemical structure of the compounds.     

Early benefits of pravastatin to experimentally induced atherosclerosis

There is little information regarding the time of hypolipidemic treatment of changes in atherosclerotic plaque, tissue cholesterol content, and also for the recovery of endothelial function. To assess the early effects of lipid-lowering treatment on these parameters, six groups of New Zealand male rabbits were studied. Animals in groups I and II were fed regular chow; groups III and IV received a 12-week 0.5% cholesterol diet followed by 12 weeks of 0.05% cholesterol diet. Finally, groups V and VI were fed a 12-week 0.5% cholesterol diet and were then shifted to a regular diet for 12 weeks. During the last four weeks, the rabbits in groups I, III, and V received low-dose pravastatin (2 mg/day), added to the diet. Group IV animals had the highest cholesterol plasma levels (vs. groups I, II, III, and V, p < 0.01) and presented atherosclerotic plaques in a more advanced stage. Nonatherogenic diet was insufficient to restore endothelial function in animals previously fed cholesterol-enriched diets (groups IV and VI). Conversely, pravastatin treatment promoted significant improvement in endothelial function and reduced the progression of atherosclerosis. Marked increase in cholesterol content was seen in aorta and liver in response to the atherogenic diet. However, neither treatment with pravastatin nor nonatherogenic diet was capable of modifying the tissue cholesterol content. Our study supports the hypothesis that the early use of statins can attenuate the progression of atherosclerosis and ameliorate endothelial function. In addition, significant changes in the tissue cholesterol pool probably need a longer period of treatment.     

Role of nitric oxide/cyclic GMP in myocardial adenosine A1 receptor-inotropic response

In this study we have determined the different signalling pathways involved in adenosine A(1)-receptor (A(1)-receptor)-dependent inhibition of contractility in rat isolated atria. N-cyclopentyladenosine (CPA) stimulation of A(1)-receptor exerts: negative inotropic response, inositol phosphates accumulation, stimulation of nitric oxide synthase (NOS), increased production of nitric oxide (NO) and cyclic GMP. Inhibitors of phospholipase C (PLC), protein kinase C (PKC), calcium/calmodulin, NOS and guanylate cyclase shifted the dose-response curve of CPA on contractility to the right. Those inhibitors also attenuated the A(1)-receptor-dependent increase in cyclic GMP and activation of NOS. These results suggest that CPA activation of A(1)-receptors exerts a negative inotropic effect associated with increased production of nitric oxide and cyclic GMP. The mechanism appears to occur secondarily to stimulation of phosphoinositide turnover via PLC activation. This, in turn, triggers cascade reactions involving calcium/calmodulin and PKC, leading to activation of NOS and soluble guanylate cyclase.     

Antihypertensive,vasodilator and antioxidant effects of a vinifera grape skin extract

Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol-free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g(-1)) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate-salt and N(G)-nitro-L-arginine methyl ester (L-NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre-contracted with norepinephrine, bolus injections of GSE induced endothelium-dependent vasodilatation that was substantially inhibited by L-NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration-dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.     

Evaluation of mandibular implant sites: correlation between panoramic and linear tomography

The reliability of the linear tomography and panoramic radiography made with X-ray equipment was evaluated (Vera View Scope X-600; Morita). The sample was composed of 20 dry human hemimandibles, in which the area selected for analysis was 1.5 cm distal from the limit set before the mental foramen. Four measurements were made. The images obtained were drawn on acetate paper and the hemimandibles cut at the demarcated area. The measurements were made using a digital electronic pachymeter. The values found for the radiographic images were compared to those obtained in the mandibular specimens and submitted to statistical evaluation by the Wilcoxon test. It was concluded that both techniques were reliable for the accomplishment of vertical linear measurements in the selected area. However, a 2.0 mm safety margin is recommended.     

Goldenhar's syndrome--case report

Goldenhar's syndrome is a rare condition described initially in the early 1950's. It is characterized by a combination of anomalies: dermal epibulbar cysts, auricular appendices and malformation of the ears. In 1963, Gorlin suggested the name oculo-auriculo-vertebral (OAV) dysplasia for this condition and also included vertebral anomalies as signs of the syndrome. The etiology of this rare disease is not fully understood, as it has shown itself variable genetically and of unclear causes. This work reports a case of Goldenhar's syndrome in an 11-year-old female, who presented all classical signs of this rare condition     

Changes in plaque fluoride levels by school-based fluoride rinsing and tablet programs in Bangladesh

The aim of this study was to evaluate the effects of school-based fluoride rinsing and tablet programs on plaque fluoride levels. A total of 42 children (8-9 years) were selected from two neighboring schools in Dhaka, Bangladesh. After caries recordings, vestibular plaque samples from the maxillary central incisors and mandibular first molars were collected and frozen on day 0 (baseline). The subjects of one school (rinsing group, n = 15) rinsed with 0.05% NaF, while those from the other school (tablet group, n = 16) used a 0.5 mg F tablet on the 5 school days during a 3-week period. The surfaces were sampled on the first and last school day every week. The fluoride and protein contents of each sample were analyzed using micro-techniques. The median plaque fluoride levels were 9.1 ppm at baseline in the rinsing group and 2.5 ppm in the tablet group (P < 0.05). This difference could in part be related to reported fluoride toothpaste usage. After 4 days on the fluoride programs, plaque fluoride levels in the rinsing group increased to 27.3, 24.5 and 14.2 ppm in the 3 consecutive weeks. The corresponding values after tablet usage were 8.0, 6.5 and 7.1 ppm, respectively. After 3 days without fluoride during the weekends, levels declined towards baseline values in both groups. Hence, the plaque fluoride levels in 8 to 9-year-old Bangladeshi children were increased by both rinsing and tablet programs, but the effect was not detectable 3 days later.     

Melatonin induces changes to serum cytokines in mice infected with the Venezuelan equine encephalomyelitis virus

We determined the influence of melatonin (MLT) on the induction of interleukin (IL)-2, IL-1 beta, IL-4, tumour necrosis factor-alpha (TNF-alpha) and gamma interferon (IFN-gamma) on mice infected with the Venezuelan equine encephalomyelitis (VEE) virus. Levels of IFN-gamma in the MLT-treated group were significantly increased (P < 0.001) when compared with the control non-infected group from day 1 to 6 post-infection (p.i.), while in infected mice treated with 500 micrograms MLT/kg of bodyweight enhanced levels of IFN-gamma were evident from 4 to 6 days p.i. No differences were detected in the levels of IL-2 between the controls, the infected mice treated with MLT and the infected untreated group, from day 2 p.i. No changes in serum levels of IL-4 were detected. In infected mice treated with MLT, blood levels of IL-1 beta were elevated almost 10-fold from day 1 to day 6 p.i. when compared to the control, the infected and the non-infected MLT-treated mice (P < 0.001). A highly significant rise (P < 0.001) of TNF-alpha was found in infected mice treated with MLT, from day 1 to 6 p.i. when compared to the other groups. A significant rise (P < 0.001) was also evident in the infected non-MLT-treated group and a less pronounced rise in the non-infected mice treated with MLT when compared to controls. The blockade of IFN-gamma and TNF-alpha did not inhibit the protective effect of MLT but when IL-1 beta was neutralized, 100% of the infected mice died suggesting that IL-1 beta induced by MLT treatment is a target cytokine to generate an immune response against the viral infection.     

Long lasting protection against canine kala-azar using the FML-QuilA saponin vaccine in an endemic area of Brazil (São Gonçalo do Amarante,RN)

Naturally exposed dogs of an endemic area were vaccinated with the fucose mannose ligand (FML) antigen of Leishmania donovani in formulation with QuilA saponin. The 100% of vaccinees were seropositive to FML and showed intradermal reaction to L. donovani lysate, 2 months after vaccination. The absorbency values and size of intradermal reaction were both significantly higher in vaccinees than in controls along a 3.5 years period (ANOVA, P<0.0001). The 25% of the control animals (two dogs on the first year and six dogs on the fourth year, respectively) and 5% of the vaccinees (one dog during the fourth year) developed clinical and fatal disease until the end of experiment. This difference was significant (chi(2)=3.93, P<0.05). This means that 95% protection against kala-azar was achieved in vaccinees, after FML-QuilA vaccination (80% of vaccine efficacy (VE)). Leishmania infection was also confirmed, 3.5 years after vaccination, in saline controls that showed positive polymerase chain reaction (PCR) for Leishmania DNA and FML-serology with no intradermal reaction. Higher seropositivities and intradermal reactions with no Leishmanial DNA were detected in vaccinees. The FML-QuilA vaccine induced a significant, long lasting and strong protective effect against canine kala-azar in the field.     

Validation of a questionnaire for measurement of beliefs about the climacteric

OBJECTIVE: To design an instrument for measuring beliefs about the social, psychological, and physiological consequences of women's climacteric stage. MATERIAL AND METHODS: The study included 340 women affiliated to Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (Institute for Social Services and Security for State Workers, ISSSTE) (age mean = 49.46, (SD 7.92). The mean number of pregnancies in the sample was 3.75 (SD 2.57), and the mean number of born children was 3.21 (SD 2.19); 48% of women were premenopausal, 10.9% perimenopausal, and 40.6% postmenopausal. The instrument consisted of 25 items. RESULTS: A factorial analysis with Varimax rotation was carried out. Four factors were confirmed: disadvantages (alpha = 0.769), advantages (alpha = 0.839), physiological (alpha = 0.659), and psychological (alpha = 0.711). CONCLUSION: This instrument shows good internal consistency, and measures four climacteric belief groups: a) beliefs on disadvantages, b) beliefs on advantages, c) beliefs on physiological ailments, and d) beliefs on psychological symptoms. All three confirmed dimensions of the climacteric phase have been proposed in other studies.