Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil.

BACKGROUND: Vertical transmission of Zika virus (ZIKV) is associated with congenital malformations but the mechanism of pathogenesis remains unclear. Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted a case-control study in a cohort of Brazilian women infected with ZIKV during pregnancy. METHODS: A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV infection, 28 were classified as cases and 24 as controls based on the presence or absence of CZS in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of CZS. RESULTS: From the 817 single nucleotide variations (SNVs) included in association analyses, 22 SNVs in 17 genes were associated with CZS under an additive model (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3 and ADCY7 genes showed the most prominent effect. The association of ADCY3 and ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (P < 0.002). CONCLUSION: These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity and influence the outcome of CZS, being promising candidates for further replication studies and functional analysis.

Weight loss and frequency of body-weight self-monitoring in an online commercial weight management program with and without a cellular-connected 'smart' scale: a randomized pilot study.

Objective: Evaluate the effects of an online commercial weight management program, with and without provision of a 'smart' scale with instructions to weigh daily and weekly tailored feedback, on weight loss and the frequency of body-weight self-monitoring. Methods: Participants (N = 92; body mass index 27-40 kg/m2) were randomized to 6 months of no-cost access to the Weight Watchers Online (WWO) platform alone, or enhanced with a cellular-connected 'smart' scale, instructions to weigh daily and weekly pre-scripted email feedback (Weight Watchers Online Enhanced [WWO-E]). The number of days that weight was self-monitored (via 'smart' scale in WWO-E and manually in WWO) was recorded automatically across the 6-month trial. Objective weight was measured at baseline, 3 and 6 months. Results: While both groups achieved statistically significant weight loss, mean ± standard error weight loss did not differ between WWO-E and WWO at 3 months (5.1 ± 0.6 kg vs. 4.0 ± 0.7 kg, respectively; p = 0.257) or 6 months (5.3 ± 0.6 kg vs. 3.9 ± 0.7 kg, respectively; p = 0.116). However, a greater proportion of WWO-E lost ≥5% of initial body weight at 3 months (52.2% vs. 28.3%; p = 0.033), but not 6 months (43.5% vs. 30.4%; p = 0.280), compared with WWO. Mean ± standard deviation days with self-monitored weight was higher in WWO-E (80.5 ± 5.6; 44.7% of days) than WWO (12.0 ± 1.0; 6.7% of days; p < 0.001) across the 6-month study period. Conclusions: This is the first study to show that provision of a 'smart' scale with weekly tailored feedback substantially increased the frequency of self-weighing and the proportion of participants achieving an initial clinically significant ≥5% weight loss (52% vs. 28%) in an online commercial weight management program. Both WWO and WWO-E produced significant weight loss over 6 months. While mean weight losses were slightly greater in the enhanced group, the difference was not statistically significant in this small sample. This study provides support for the clinical utility of online commercial weight management programs and the potential for supporting technology such as 'smart' scales to improve adherence to body-weight self-monitoring and clinical outcomes.

"In vitro" antifungal activity of ozonized sunflower oil on yeasts from onychomycosis

The "In vitro" antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporonasahii, Candida tropicalis and Candida guilliermondii.

Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: importance in ARDS in septic pediatric critically ill patients.

Accumulating evidence indicates that genetic background influences the outcome of sepsis, which despite medical advances continues to be a major cause of morbidity and mortality. This study aimed to evaluate the influence of SNPs LTA +252A>G, TNF-863C>A and TNF-308G>A on susceptibility to sepsis, acute respiratory distress syndrome (ARDS), septic shock and sepsis mortality. A prospective case-control study was carried out in a Brazilian pediatric intensive care unit and included 490 septic pediatric patients submitted to mechanical ventilation and 610 healthy children. No SNP association was found with respect to sepsis susceptibility. Nevertheless, a haplotype was identified that was protective against sepsis (+252A/-863A/-308G; OR=0.65; p=0.03). We further observed protection against ARDS in TNF-308 GA genotype carriers (OR=0.29; p=0.0006) and -308A allele carriers (OR=0.40; p=0.003). In addition, increased risk for ARDS was detectable with the TNF-863 CA genotype (OR=1.83; p=0.01) and the -863A carrier status (OR=1.82; p=0.01). After stratification according to age, this outcome remained significantly associated with the -308GA genotype in infants. Finally, protection against sepsis-associated mortality was found for the TNF-308 GA genotype (OR=0.22; p=0.04). Overall, our findings document a protective effect of the TNF-308 GA genotype for the ARDS and sepsis mortality outcomes, further providing evidence for an increased risk of ARDS associated with the TNF-863 CA genotype. Trial registration (www.clinicaltrials.gov): NCT00792883.

"In vitro" antifungal activity of ozonized sunflower oil on yeasts from onychomycosis.

The "in vitro" antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporon asahii, Candida tropicalis and Candida guilliermondii.

IFNG +874 T>A single nucleotide polymorphism is associated with leprosy among Brazilians.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a low virulence mycobacterium, and the outcome of disease is dependent on the host genetics for either susceptibility per se or severity. The IFNG gene codes for interferon-γ (IFN-γ), a cytokine that plays a key role in host defense against intracellular pathogens. Indeed, single nucleotide polymorphisms (SNPs) in IFNG have been evaluated in several genetic epidemiological studies, and the SNP +874T>A, the +874T allele, more specifically, has been associated with protection against infectious diseases, especially tuberculosis. Here, we evaluated the association of the IFNG locus with leprosy enrolling 2,125 Brazilian subjects. First, we conducted a case-control study with subjects recruited from the state of São Paulo, using the +874 T>A (rs2430561), +2109 A>G (rs1861494) and rs2069727 SNPs. Then, a second study including 1,370 individuals from Rio de Janeiro was conducted. Results of the case-control studies have shown a protective effect for +874T carriers (OR(adjusted) = 0.75; p = 0.005 for both studies combined), which was corroborated when these studies were compared with literature data. No association was found between the SNP +874T>A and the quantitative Mitsuda response. Nevertheless, the spontaneous IFN-γ release by peripheral blood mononuclear cells was higher among +874T carriers. The results shown here along with a previously reported meta-analysis of tuberculosis studies indicate that the SNP +874T>A plays a role in resistance to mycobacterial diseases.

IFNG +874 T>A single nucleotide polymorphism is associated with leprosy among Brazilians

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a low virulence mycobacterium, and the outcome of disease is dependent on the host genetics for either susceptibility per se or severity. The IFNG gene codes for interferon-γ (IFN-γ), a cytokine that plays a key role in host defense against intracellular pathogens. Indeed, single nucleotide polymorphisms (SNPs) in IFNG have been evaluated in several genetic epidemiological studies, and the SNP +874T>A, the +874T allele, more specifically, has been associated with protection against infectious diseases, especially tuberculosis. Here, we evaluated the association of the IFNG locus with leprosy enrolling 2,125 Brazilian subjects. First, we conducted a case-control study with subjects recruited from the state of São Paulo, using the +874 T>A (rs2430561), +2109 A>G (rs1861494) and rs2069727 SNPs. Then, a second study including 1,370 individuals from Rio de Janeiro was conducted. Results of the case-control studies have shown a protective effect for +874T carriers (OR(adjusted) = 0.75; p = 0.005 for both studies combined), which was corroborated when these studies were compared with literature data. No association was found between the SNP +874T>A and the quantitative Mitsuda response. Nevertheless, the spontaneous IFN-γ release by peripheral blood mononuclear cells was higher among +874T carriers. The results shown here along with a previously reported meta-analysis of tuberculosis studies indicate that the SNP +874T>A plays a role in resistance to mycobacterial diseases(AU)

Genetic, epidemiological and biological analysis of interleukin-10 promoter single-nucleotide polymorphisms suggests a definitive role for -819C/T in leprosy susceptibility.

Leprosy is a complex infectious disease influenced by genetic and environmental factors. The genetic contributing factors are considered heterogeneous and several genes have been consistently associated with susceptibility like PARK2, tumor necrosis factor (TNF), lymphotoxin-alpha (LTA) and vitamin-D receptor (VDR). Here, we combined a case-control study (374 patients and 380 controls), with meta-analysis (5 studies; 2702 individuals) and biological study to test the epidemiological and physiological relevance of the interleukin-10 (IL-10) genetic markers in leprosy. We observed that the -819T allele is associated with leprosy susceptibility either in the case-control or in the meta-analysis studies. Haplotypes combining promoter single-nucleotide polymorphisms also implicated a haplotype carrying the -819T allele in leprosy susceptibility (odds ratio (OR)=1.40; P=0.01). Finally, we tested IL-10 production in peripheral blood mononuclear cells stimulated with Mycobacterium leprae antigens and found that -819T carriers produced lower levels of IL-10 when compared with non-carriers. Taken together, these data suggest that low levels of IL-10 during the disease outcome can drive patients to a chronic and unprotective response that culminates with leprosy.

Suppression of T and B cell responses by Pterodon pubescens seeds ethanolic extract.

The anti-arthritic property of hydro alcoholic extract of Pterodon pubescens seeds was previously demonstrated using the Collagen Induced Arthritis (CIA) in mice, the most similar arthritis experimental model to human rheumatoid arthritis. This disease is characterized by chronic inflamed joints resulting from exacerbated functions of macrophages and T and B lymphocytes. Anti-inflammatory and antinociceptive activities by ethanolic extract of Pterodon pubescens seeds (EEPp) have been also reported. This study describes the effects of EEPp on T and B lymphocytes functions from healthy mice. Delayed Type Hypersensitivity (DTH), in vivo antibody production, T and B lymphocyte proliferation and NO production were determined. Mice treated orally for 7 days with EEPp had inhibited 58% of B cell antibody production (10(-3) mg kg(-1) b.wt.) and 33% of the DTH response (10(-4) mg kg(-1) b.wt.), also reducing tissue leukocyte infiltration. EEPp (10(-2) mg mL(-1)) also inhibited in vitro T (89%) and B (68%) lymphocytes proliferation and NO production (53%) by macrophage cell line J774. The immunosuppression here described for EEPp supports its potential therapeutic use to control exacerbated humoral and/or cellular immune response as in autoimmune and chronic inflammatory diseases.

Action of ozonized water in preclinical inflammatory models.

Ozonized water increases oxygen local tension. The ozone by itself produces inflammatory reactions in lung epithelium. The action of ozonized water during the inflammatory process was investigated. In rat paw edema induced by carrageenin, the inflammatory process was stimulated by ozonized water (1.2 microg, p.o.) when applied 30 min prior to the induction. In the inflammatory process induced by Freund's Complete Adjuvant, the ozonized water did not interfere in the inflammatory reaction. Furthermore, in gastric ulcers models induced by stress, there was a significant reduction in the incidence of ulcers types I, II and III (P<0.05, Student's t -test).

Angiotensin-II-induced angiogenesis in sponge implants in mice.

Stimulators of angiogenesis hold potential in promoting the development of collateral circulation in ischaemic tissue and accelerating would healing, but promote pathological vasoformation in angiogenesis-dependent diseases (solid tumours, atherosclerosis). The renin-angiotensin system is implicated in both beneficial angiogenesis and pathological vascular growth. We investigated the angiogenic activity of angiotensin II (AII) in a sponge implant model in mice; this peptide enhanced angiogenesis, as well as glycosaminoglycan (GAG, chondroitin sulfate proteoglycan) and protein synthesis in sponge matrix in mice in a dose-dependent fashion. Extensive angiogenesis was achieved with AII (1 microgram), which gave no significant increase in wet weight and protein and only a small effect on GAG. In the implants treated with AII (2 micrograms) no further increase in angiogenesis was observed, whereas a marked effect was shown in wet weight (326 +/- 15 vs. 424 +/- 27 mg), total protein (18 +/- 1 vs. 25 +/- 1 micrograms/ww) and GAG (98 +/- 10 vs. 160 +/- 13 ng/ww). The local blood flow has been determined by measuring the washout rate of 133Xe injected into the implants, correlated with histological evidence of vessel growth. This model of angiogenesis has allowed sequential studies of fibrovascular tissue infiltration simultaneously with histological and biochemical parameters of angiogenesis.