Synthesis and evaluation of antimicrobial and anticonvulsant activities of some new 3-[2- (5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxymethylthiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and investigation of their structure-activity relationships

In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I-XII) and 3-[2-(4-carbethoxymethylthiazol-2-yl)imino-4-thiazoldinon-5-ylidenel-5-substituted/nonsubstituted IH-indole-2-one (XIII-XX) systems were synthesized. The structures were confirmed by spectral methods (UV, IR, 1H-NMR, 13C-NMR, 13C-DEPT (135), electron impact mass spectrometry) and elemental analysis. All compounds were tested for in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found to be active. Especially, compound I was more active than cefuroxime sodium (CAS 56238-63-2) which was used as a standard, and the activity of compound XII was close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228. Primary screening for antituberculous activity was conducted at 6.25 microg/ml against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. The anticonvulsant activities of selected prototoype compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200 mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice.     

Preliminary information on sandflies in the north of Paraná State, Brazil

The results from sandfly collections in 10 municipalities in Paraná State, Brazil are reported. The captures were done using Falc?o traps in homes, domestic animal shelters and forested areas, from 1999 to 2002. A total of 13,653 sandflies were collected from 10 species of the genera Brumptomyia, Expapillata, Evandromyia, Migonemyia, Pintomyia, Nyssomyia and Psathyromyia. The species Nyssomyia neivai was predominant in five municipalities. N. whitmani predominated in the other five, in greater numbers than for N. neivai in the first five municipalities. High frequencies of sand flies were found in forests, homes, pigpens and henhouses. Investigations on the participation of domestic animals and phlebotomine fauna in the epidemiology of tegumentary leishmaniasis should be routine in health surveillance, especially where this disease is endemic.     

Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer

BACKGROUND: Alcohol intake and tobacco smoke, in addition to other environmental and genetic factors, have been associated with head and neck cancer. We evaluated the role of metabolic enzyme polymorphisms on the risk of head and neck cancer in a hospital-based case-control study. METHODS: CYP1A1MspI, CYP2E1PstI, GSTM1, and GSTT1polymorphisms were evaluated in 103 histologically confirmed head and neck cancer cases and 102 controls by means of polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: GSTM1null increased the risk of head and neck cancer (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 1.24-3.79), oral cancer (OR, 2.8; 95% CI, 1.28-5.98), and pharyngeal cancer (OR, 2.2; 95% CI, 1.08-4.63). CYP2E1PstI polymorphism indicated a risk for oral cancer (OR, 3.6; 95% CI, 1.29-11.56). The joint effect of GSTM1 null and CYP1A1 polymorphism increased the risk of head and neck cancer (OR, 2.4; 95% CI, 1.13-5.10). CONCLUSIONS: GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer.     

A novel type of familial proximal axonal dystrophy: three cases and a review of the axonal dystrophies

Three related infants of Roma ancestry, two of them siblings, showed hypotonia, predominantly axial, from birth, difficulty swallowing, myoclonic seizures, and respiratory difficulty. Dysmorphic features, principally micrognathia were present. EEGs showed focal epileptiform abnormalities. All three died in their 5th month from respiratory insufficiency complicated by pneumonia. Autopsy showed small brains without malformation. Microscopy revealed numerous axonal spheroids involving particularly the brain stem and spinal cord, with especial prominence in the middle cerebellar peduncle, the anterior part of the thalamic reticular nuclei, and the anterior horns and columns of the spinal cord. Spheroids that appeared to be on axons of lower motor neurons were especially large. No spheroids were seen in peripheral nerves; electron microscopy did not show spheroids in skin. By electron microscopy spheroids contained neurofilaments, sparse mitochondria, and electron dense granules. The material did not allow identification of microtubules. Closely packed vesicles excluded neurofilamanets from the center of many spheroids, especially in the middle cerebellar peduncle. Sprouting of axons from the surface of many spheroids was seen. This disease is distinct from the well described type of infantile neuroaxonal dystrophy (Seitelberger's disease) in view of the distribution of spheroids, presence of spheroids on proximal rather than distal parts of axons, sparing of the peripheral nerves, lack of staining for synuclein, presence of sprouting, and lack of membranous profiles in the spheroids. A review of reported types of axonal dystrophy has not shown identical cases.     

Progression of periodontitis in a sample of regular and irregular compliers under maintenance therapy: a 3-year follow-up study

Background: To our knowledge, prospective studies (matched for sex, smoking, and diabetes) that investigated the influence of compliance in the progression of periodontitis and tooth loss in periodontal maintenance therapy (PMT) programs were not previously reported. Methods: A total of 58 regular complier (RC) and 58 erratic complier (EC) individuals were recruited from a prospective cohort with 238 patients under PMT and matched by sex, diabetes, and smoking habits. A full‐mouth periodontal examination that included bleeding on probing (BOP), probing depths (PDs), clinical attachment levels, and number of teeth were determined at all PMT visits during a 3‐year interval. The influence of variables of interest was tested through multivariate logistic regression. Results: The progression of periodontitis and tooth loss was significantly lower among RC compared to EC patients. A higher progression of periodontitis was observed among EC patients who smoked. The final logistic model for the progression of periodontitis in the RC group included smoking (odds ratio [OR]: 4.2) and >30% of sites with BOP (OR: 2.8), and the final logistic model for the progression of periodontitis in the EC group included smoking (OR: 7.3), >30% of sites with BOP (OR: 3.2), PDs of 4 to 6 mm in 10% of sites (OR: 3.5), diabetes (OR: 1.9), and number of lost teeth (OR: 3.1). Conclusions: RC patients presented a lower progression of periodontitis and tooth loss compared to EC patients. This result highlighted the influence of the pattern of compliance in maintaining a good periodontal status. Moreover, important risk variables such as smoking and diabetes influenced the periodontal status and should be considered when determining the risk profile and interval time for PMT visits.     

Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality

The proliferation of counterfeit and poor-quality drugs is a major public health problem; especially in developing countries lacking adequate resources to effectively monitor their prevalence. Simple and affordable field methods provide a practical means of rapidly monitoring drug quality in circumstances where more advanced techniques are not available. Therefore, we have evaluated refractometry, colorimetry and a technique combining both processes as simple and accurate field assays to rapidly test the quality of the commonly available antimalarial drugs; artesunate, chloroquine, quinine, and sulfadoxine. Method bias, sensitivity, specificity and accuracy relative to high-performance liquid chromatographic (HPLC) analysis of drugs collected in the Lao PDR were assessed for each technique. The HPLC method for each drug was evaluated in terms of assay variability and accuracy. The accuracy of the combined method ranged from 0.96 to 1.00 for artesunate tablets, chloroquine injectables, quinine capsules, and sulfadoxine tablets while the accuracy was 0.78 for enterically coated chloroquine tablets. These techniques provide a generally accurate, yet simple and affordable means to assess drug quality in resource-poor settings.     

Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease

Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of atherosclerosis through the production of inflammatory and anti-inflammatory cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8, CXCL9, CXCL10, IFN-gamma and IL-10 in vitro as well as the expression of the CCR2 and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy controls in the presence or absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-gamma mRNA and, after stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control group. We also detected higher levels of CCL2 and CXCL8 in supernatants of oxLDL-stimulated PBMCs from CAD patients than in corresponding supernatants from controls. Patients with CAD had a higher percentage of constitutive CCR2(+) and CXCR3(+) cells after stimulation with oxLDL. Among CAD patients, the main differences between the stable (SA) and unstable angina (UA) groups were lower IL-10 mRNA production in the latter group. Altogether, our data suggest that PBMCs from CAD patients are able to produce higher concentrations of chemokines and cytokines involved in the regulation of monocyte and lymphocyte migration and retention in atherosclerotic lesions.     

Association between maternal periodontitis and an increased risk of preeclampsia

BACKGROUND: Periodontal disease has been considered a systemic exposure implicated in a higher risk of adverse pregnancy outcomes. The aim of the present study was to determine whether maternal periodontitis is associated with an increased risk of preeclampsia. METHODS: A case-control study was conducted in a public hospital in Belo Horizonte, Brazil. During the study period, 588 women, aged 14 to 46 years, were deemed eligible and had data available for analysis. Maternal demographic and medical data were collected from medical records. Preeclampsia was defined as blood pressure >140/90 mm Hg and > or =1+ proteinuria after 20 weeks of gestation. A periodontal examination was performed postpartum. Maternal periodontitis was defined as the presence of four or more teeth with one or more sites with a probing depth > or =4 mm and clinical attachment loss > or =3 mm at the same site. The effects of maternal age, chronic hypertension, primiparity, smoking, alcohol use, and number of prenatal visits were analyzed. Adjusted odds ratios (ORs) for preeclampsia were calculated using multivariate logistic regression. RESULTS: The prevalence of periodontitis was 63.9% and preeclampsia was 18.5%. Variables associated with preeclampsia were chronic hypertension (OR = 4.10; 95% confidence interval [CI] = 2.0 to 8.4; P = 0.001), primiparity (OR = 2.40; 95% CI = 1.5 to 3.9; P = 0.004), maternal age (OR = 1.07; 95% CI = 1.0 to 1.1; P = 0.001), and maternal periodontitis (OR = 1.88; 95% CI = 1.1 to 3.0; P = 0.001). CONCLUSION: Maternal periodontitis was determined to be associated with an increased risk of preeclampsia.