Molecular electrostatic potential-anthelmintic activity relationships of 5H-mebendazole and some related heterocyclic carbamates

5H-Mebendazole and some related heterocyclic methyl carbamates were synthesized and their anthelmintic activity against Caenorhabditis elegans was determined. In order to study the influence of the heteroaromatic region with regard to the carbamate moiety on biological activity, the molecular electrostatic potentials (MEP) of all structures were calculated and a structure-activity relationship (SAR) was established. The electrostatic pattern of activity includes two minima of the carbamate moiety, a third heterocyclic minimum, and a pi-electronic region.     

Structure-activity relationships among di- and tetramine disulfides related to benextramine

The synthesis and irreversible alpha-blocking activity in the rat vas deferens of a series of tetra- and diamine disulfides 2-38, structural analogues of benextramine (BHC), are described. All compounds containing a central cystamine moiety displayed an irreversible alpha-adrenergic blockade at concentrations ranging from 10(-4) to 6 X 10(-6)M. Potency was increased in cystamines N,N'-disubstituted with 6-aminohexyl groups, especially when the outer nitrogen atoms bear arylalkyl substituents or are enclosed in a ring. However, N,N,N',N'-tetrasubstituted cystamines were poor blockers. Structural specificity in the outer portion of the tetramine disulfide is low, since many types of substituents gave rise to potent alpha-blockers. Even replacement of the outer amines with nonbasic ethers or amides was observed to maintain irreversible alpha-blockade.     

Comparative, Clinico-Epidemiologic Study of Schistosoma mansoni Infections in Travellers and Immigrants in Spain

The study presented here aimed to contrast the marked clinical differences in the presentation of Schistosoma mansoni-induced infection between immigrants and travellers entering Spain from endemic regions, and to elucidate the therapeutic implications of these infections. A total of 200 African immigrants and 80 travellers with schistosomiasis were included in the study. Among the immigrants, 25 patients were diagnosed with Schistosoma mansoni infection; 15 presented with nonspecific symptoms, and 10 were asymptomatic. Hepatosplenomegaly was observed in nine. Among the travellers, 14 were diagnosed with Schistosoma mansoni infection; four were asymptomatic, four had Katayama syndrome, four had diarrhoea, and two had prostatitis. All of the patients were treated with praziquantel. Patients diagnosed with Katayama syndrome received praziquantel and dexamethasone for 3 days, with the praziquantel treatment being repeated at 3–4 weeks. The significant differences observed in the clinical presentation of Schistosoma mansoni-induced infection, indicate that a well-differentiated therapeutic strategy is required when this infection is diagnosed in a non-immune (traveller) or a semi-immune (immigrant) patient. Electronic Publication     

Inflammatory responses in blood samples of human immunodeficiency virus-infected patients with pulmonary infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-alpha) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-alpha, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1beta, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-alpha levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).     

Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).     

Evaluation of the Determine Rapid Syphilis TP assay using sera

The Abbott Determine Rapid Syphilis TP assay is a treponemal test that can be used in resource-poor settings that lack laboratory facilities. However, this test has not been extensively evaluated. We measured its sensitivity and specificity by using stored serum specimens (n = 567) from all persons who tested Treponema pallidum hemagglutination assay (TPHA) positive (n = 250) or TPHA indeterminate (n = 17) in the year 2001 and the first 300 patients in 2001 who tested TPHA negative at the Evandro Chagas Research Institute in Rio de Janeiro, Brazil. This rapid assay was independently interpreted by three different observers. With TPHA results as the reference, sensitivity ranged between readers from 95.6 to 98.4% and specificity ranged from 97.3 to 95.7%. There was little interreader variability in the interpretation of results, with approximately 98% agreement for all reader combinations. Of samples from persons with human immunodeficiency virus (HIV) infection (n = 198), sensitivity was 96.9 to 99.2% and it was 94.4 to 96.3% among HIV-negative persons (n = 127). Specificity was 92.4 to 95.5% among HIV-positive persons and 97.2 to 100% among HIV-negative persons. We found this test to have high sensitivity and specificity and little interreader variability, indicating that it may be easily used in resource-poor settings without laboratory facilities. Further studies are needed using this test on whole blood and under the clinical conditions for which it is intended.     

Gut Microbiota Profile and Its Association with Clinical Variables and Dietary Intake in Overweight/Obese and Lean Subjects: A Cross-Sectional Study

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.     

Determinants of the Consumption of Regular Soda,Sport, and Energy Beverages in Spanish Adolescents

Increasing sugar-sweetened beverages (SSB) consumption and associated health impacts warrant health-policy action. We assessed associations of socioeconomic and lifestyle variables with adolescents’ consumption of regular soda (RSD), sport (SD), and energy (ED) drinks. Cross-sectional study of 3930 Spanish adolescents (2089 girls, 1841 boys) aged 13–18 years). We compared frequency of consuming each SSB type (European Food Safety Authority questionnaire) with sociodemographic and lifestyle variables (standardized questions). RSD, SD, and ED were consumed at least weekly by 72.7%, 32.3%, and 12.3% of participants, respectively, and more frequently (p < 0.001) by boys, compared to girls. Multivariate ordinal logistic regression showed inverse association between RSD, SD, and ED consumption and parental occupation-based socioeconomic status (p < 0.01). Daily smoking was associated (p < 0.001) with higher ED (OR 3.64, 95% CI 2.39–5.55) and RSD (OR 2.15, 95% CI 1.56–2.97) consumptions. SD intake was associated inversely with smoking (OR 0.60, 95% CI 0.40–0.89, p = 0.012) and directly with physical activity (OR 2.93, 95% CI 2.18–3.95, p < 0.001). School performance was lower among ED (OR 2.14, 95% CI, 1.37–3.35, p = 0.001) and RSD (OR 1.81, 95% CI 1.24–2.64, p = 0.002) consumers, compared to SD. Maleness and low socioeconomic status predicted SSB consumption. Smoking and low school performance were associated with higher ED and RSD intakes.