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1.
Contact Dermatitis ; 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39367763

ABSTRACT

BACKGROUND: Propolis types differ regarding their chemical composition. OBJECTIVES: To compare patch test results based on Brazilian (Green) propolis with data based on Chinese (poplar-type) propolis, and to evaluate the specifications of raw materials used for the PT preparations. METHODS: In the Information Network of Departments of Dermatology (IVDK), 1290 consecutive patients were patch tested with Brazilian (Green) propolis (NH400, SmartPractice Europe). Patch test reactivity was compared with results obtained with Chinese (poplar-type) propolis (NA71, SmartPractice Europe) by calculating frequencies and corresponding 95% confidence intervals. Data on the specifications of raw materials used for NH400 and NA71 were obtained from the manufacturer. RESULTS: Positive reactions to NH400 were found in 303 (23.5%) patients with unclear clinical relevance in most cases. Patients reacting to NH400 were less often sensitised to fragrances and colophony, but more often to nickel sulphate and cobalt chloride than patients reacting to NA71. The NH400 batch used contained high levels of aerobic bacteria, and was not purified by ethanolic extraction. CONCLUSIONS: Pattern of concomitant reactivity along with raw material properties suggests that the high frequency of positive reactions to NH400 may primarily result from bacterial contamination or impurities in the PT preparation rather than from propolis constituents.

2.
Enferm Infecc Microbiol Clin (Engl Ed) ; 40(8): 445-448, 2022 10.
Article in English | MEDLINE | ID: mdl-36195408

ABSTRACT

INTRODUCTION: Clostridioides difficile biofilms are believed to protect the pathogen from antibiotics, in addition to potentially contributing to recurrent infections. METHODOLOGY: Biofilm production of 102 C. difficile isolates was determined using the crystal violet staining technique, and detachment assays were performed. The expression levels of cwp84 and slpA genes were evaluated by real-time PCR on selected isolates. RESULTS: More than 70% of isolates (75/102) were strong biofilm producers, and the highest detachment of biofilm was achieved with the proteinase K treatment (>90%). The overall mean expression of cwp84 was higher in RT027 than in RT001 (p=0.003); among strong biofilm-producing strains, the slpA expression was lower in RT027 than in RT001 (p<0.000). CONCLUSIONS: Proteins seem to have an important role in the biofilm's initial adherence and maturation. slpA and cwp84 are differentially expressed by C. difficile ribotype and biofilm production level.


Subject(s)
Clostridioides difficile , Anti-Bacterial Agents , Bacterial Proteins/genetics , Biofilms , Clostridioides , Clostridioides difficile/genetics , Endopeptidase K , Gentian Violet , Mexico
3.
Foods ; 11(16)2022 Aug 09.
Article in English | MEDLINE | ID: mdl-36010384

ABSTRACT

Recent advances in nuclear magnetic resonance (NMR) have led to the development of low-field benchtop NMR systems with improved sensitivity and resolution suitable for use in research and quality-control laboratories. Compared to their high-resolution counterparts, their lower purchase and running costs make them a good alternative for routine use. In this article, we show the adaptation of a method for predicting the consumer acceptability of mandarins, originally reported using a high-field 400 MHz NMR spectrometer, to benchtop 60 MHz NMR systems. Our findings reveal that both instruments yield comparable results regarding sugar and citric acid levels, leading to the development of virtually identical predictive linear models. However, the lower cost of benchtop NMR systems would allow cultivators to implement this chemometric-based method as an additional tool for the selection of new cultivars.

4.
Microb Drug Resist ; 27(12): 1672-1676, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34037477

ABSTRACT

In this study, we report the results of the epidemiological analysis of Clostridioides difficile ribotypes (RTs) and antimicrobial susceptibility testing. Most isolates were RT027, representing 73% (84/115) of isolates. No isolates with reduced susceptibility to fidaxomicin were found; however, 38 (33.04%) isolates had reduced susceptibility to metronidazole, and 7 isolates (6.1%) had reduced susceptibility to vancomycin. These findings highlight the need for continuous surveillance of C. difficile RTs and antimicrobial susceptibility testing.


Subject(s)
Anti-Bacterial Agents/pharmacology , Clostridioides difficile/drug effects , Clostridioides difficile/genetics , Drug Resistance, Bacterial/genetics , Fidaxomicin/pharmacology , Genes, Bacterial , Humans , Metronidazole/pharmacology , Mexico , Microbial Sensitivity Tests , Ribotyping , Vancomycin/pharmacology
5.
Nephrology (Carlton) ; 26(7): 603-612, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33864650

ABSTRACT

Chronic kidney disease (CKD) is a serious public health problem and its prevalence is growing in many countries, often related to issues resulting from the lifestyle in growing economies and the population's life expectancy. Nutritional therapy is a beneficial but still neglected strategy for preventing CKD and delaying disease progression. The aim of this study was to assess the association of dietary patterns with CKD development and progression. Observational studies conducted in adult humans and the correlation between the adopted dietary pattern and prevalent and incident cases of CKD were assessed. A significant association was observed between unhealthy dietary patterns and an increased risk of developing or worsening CKD, as well as an adverse effect. Whereas healthy eating patterns characterized by the consumption of fruit, vegetables and dietary fibre showed nephroprotective outcomes.


Subject(s)
Diet , Renal Insufficiency, Chronic/prevention & control , Adult , Disease Progression , Humans , Renal Insufficiency, Chronic/etiology
6.
Catheter. cardiovasc. interv ; 97(suppl. 1): S55-S56, Apr., 2021.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1349087

ABSTRACT

BACKGROUND: While dual antiplatelet therapy (DAPT) constitutes the cornerstone of post-PCI pharmacotherapy, duration of DAPT in high bleeding risk (HBR) patients has not been fully defined especially with regard to sex. The results from the Onyx ONE Clear trial demonstrated favorable safety and efficacy after PCI with 1-month dual antiplatelet therapy (DAPT) in HBR patients treated with Resolute Onyx drug-eluting stents (DES). We sought to evaluate impact of sex on clinical outcomes in this trial. METHODS: In this prespecified subgroup analysis from Onyx ONE Clear, patients were divided into 2 groups according to sex. Primary endpoint was cardiac death or myocardial infarction (MI) from 1 month to 1 year. RESULTS: A total of 487 female patients (32%) and 1019 males (68%) were free from major ischemic events 1-month after PCI and were transitioned to single antiplatelet therapy.Women were older (p<0.001), had more HBR criteria (p=0.02), and higher rates of moderate/severe calcific lesions (p=0.03) compared to men. Men had higher rates of previous MI (p=0.003), atrial fibrillation (p=0.001), and multivessel coronary artery disease (p<0.001). Clinical outcomes between 1 and 12 months are shown in (Figure) and were similar for males and females except for target vessel revascularization which was greater for males (p=0.04). CONCLUSIONS: In HBR patients treated with Resolute Onyx DES and an abbreviated DAPT course of one month, rates of the primary endpoint of cardiac death or MI between 1 and 12 months were low and did not show any sex-based differences. These data support the use of an abbreviated DAPT regimen in men and women with HBR after PCI with Resolute Onyx DES.


Subject(s)
Sex , Coronary Artery Disease , Drug-Eluting Stents
7.
Article in English, Spanish | MEDLINE | ID: mdl-33714640

ABSTRACT

INTRODUCTION: Clostridioides difficile biofilms are believed to protect the pathogen from antibiotics, in addition to potentially contributing to recurrent infections. METHODOLOGY: Biofilm production of 102 C. difficile isolates was determined using the crystal violet staining technique, and detachment assays were performed. The expression levels of cwp84 and slpA genes were evaluated by real-time PCR on selected isolates. RESULTS: More than 70% of isolates (75/102) were strong biofilm producers, and the highest detachment of biofilm was achieved with the proteinase K treatment (>90%). The overall mean expression of cwp84 was higher in RT027 than in RT001 (p=0.003); among strong biofilm-producing strains, the slpA expression was lower in RT027 than in RT001 (p<0.000). CONCLUSIONS: Proteins seem to have an important role in the biofilm's initial adherence and maturation. slpA and cwp84 are differentially expressed by C. difficile ribotype and biofilm production level.

8.
J Microbiol Methods ; 175: 105974, 2020 08.
Article in English | MEDLINE | ID: mdl-32531232

ABSTRACT

There has been an increase in the incidence and severity of Clostridioides difficile infection (CDI) worldwide, and strategies to control, monitor, and diminish the associated morbidity and mortality have been developed. Several typing methods have been used for typing of isolates and studying the epidemiology of CDI; serotyping was the first typing method, but then was replaced by pulsed-field gel electrophoresis (PFGE). PCR ribotyping is now the gold standard method; however, multi locus sequence typing (MLST) schemes have been developed. New sequencing technologies have allowed comparing whole bacterial genomes to address genetic relatedness with a high level of resolution and discriminatory power to distinguish between closely related strains. Here, we review the most frequent C. difficile ribotypes reported worldwide, with a focus on their epidemiology and genetic characteristics.


Subject(s)
Clostridioides difficile , Clostridium Infections , Genome, Bacterial , Ribotyping/methods , Clostridioides difficile/classification , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Humans , Molecular Epidemiology
9.
N. Engl. j. med ; 382(13): 1208-1218, Mar., 2020. tab., graf.
Article in English | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1053448

ABSTRACT

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)


Subject(s)
Coronary Artery Disease/drug therapy , Combined Modality Therapy , Sirolimus , Drug-Eluting Stents , Polymers , Double-Blind Method
10.
Mol Biol Evol ; 37(1): 295-299, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31504749

ABSTRACT

HYpothesis testing using PHYlogenies (HyPhy) is a scriptable, open-source package for fitting a broad range of evolutionary models to multiple sequence alignments, and for conducting subsequent parameter estimation and hypothesis testing, primarily in the maximum likelihood statistical framework. It has become a popular choice for characterizing various aspects of the evolutionary process: natural selection, evolutionary rates, recombination, and coevolution. The 2.5 release (available from www.hyphy.org) includes a completely re-engineered computational core and analysis library that introduces new classes of evolutionary models and statistical tests, delivers substantial performance and stability enhancements, improves usability, streamlines end-to-end analysis workflows, makes it easier to develop custom analyses, and is mostly backward compatible with previous HyPhy releases.


Subject(s)
Genetic Techniques , Phylogeny , Software
11.
PLoS One ; 14(7): e0220671, 2019.
Article in English | MEDLINE | ID: mdl-31365590

ABSTRACT

Clostridium [Clostridioides] difficile infection (CDI) is one of the leading causes of diarrhea associated with medical care worldwide, and up to 60% of patients with CDI can develop a recurrent infection (R-CDI). A multi-species microbiota biofilm model of C. difficile was designed to evaluate the differences in the production of biofilms, sporulation, susceptibility to drugs, expression of sporulating (sigH, spo0A), quorum sensing (agrD1, and luxS), and adhesion-associated (slpA and cwp84) pathway genes between selected C. difficile isolates from R-CDI and non-recurrent patients (NR-CDI). We obtained 102 C. difficile isolates from 254 patients with confirmed CDI (66 from NR-CDI and 36 from R-CDI). Most of the isolates were biofilm producers, and most of the strains were ribotype 027 (81.374%, 83/102). Most C. difficile isolates were producers of biofilm (100/102), and most were strongly adherent. Sporulation was higher in the R-CDI than in the NR-CDI isolates (p = 0.015). The isolates from R-CDI patients more frequently demonstrated reduced susceptibility to vancomycin than isolates of NR-CDI patients (27.78% [10/36] and 9.09% [6/66], respectively, p = 0.013). The minimum inhibitory concentrations for vancomycin and linezolid against biofilms (BMIC) were up to 100 times and 20 times higher, respectively, than the corresponding planktonic MICs. Expression of sigH, spo0A, cwp84, and agrD1 was higher in R-CDI than in NR-CDI isolates. Most of the C. difficile isolates were producers of biofilms with no correlation with the ribotype. Sporulation was greater in R-CDI than in NR-CDI isolates in the biofilm model of C. difficile. The R-CDI isolates more frequently demonstrated reduced susceptibility to vancomycin and linezolid than the NR-CDI isolates in both planktonic cells and biofilm isolates. A higher expression of sporulating pathway (sigH, spo0A), quorum sensing (agrD1), and adhesion-associated (cwp84) genes was found in R-CDI than in NR-CDI isolates. All of these factors can have effect on the recurrence of the infection.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Clostridium Infections/microbiology , Drug Resistance, Bacterial , Linezolid/pharmacology , Spores, Bacterial/growth & development , Vancomycin/pharmacology , Virulence Factors/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biofilms/drug effects , Clostridioides difficile/drug effects , Clostridioides difficile/physiology , Clostridium Infections/drug therapy , Clostridium Infections/metabolism , Humans , Microbiota , Quorum Sensing , Recurrence , Ribotyping , Spores, Bacterial/drug effects , Virulence Factors/genetics
12.
Microb Drug Resist ; 24(4): 386-392, 2018 May.
Article in English | MEDLINE | ID: mdl-29485939

ABSTRACT

OBJECTIVE: To assess drug susceptibility and characterize Clostridium difficile ribotypes in isolates from two tertiary-care hospitals in Mexico. METHODS: Isolates were evaluated for genotyping, antimicrobial susceptibility testing and detection of mutations associated with drug resistance. PCR ribotyping was performed using a combination of gel-based and capillary electrophoresis-based approaches. RESULTS: MIC50 and MIC90 were ≥128 mg/L for ciprofloxacin, erythromycin, clindamycin, and rifampicin. There was no reduced susceptibility to metronidazole or tetracycline; however, reduced susceptibility to vancomycin (≥4 mg/L) and fidaxomicin (≥2 mg/L) was detected in 50 (40.3%) and 4 (3.2%) isolates, respectively. Furthermore, the rpoB Arg505Lys mutation was more frequently detected in isolates with high minimum inhibitory concentration (MIC) to rifampicin (≥32 mg/L) (OR = 52.5; 95% CI = 5.17-532.6; p < 0.000). Of the 124 C. difficile isolates recovered, 84 (66.7%) were of ribotype 027, 18 (14.5%) of ribotype 001, and the remainder were other ribotypes (353, 255, 220, 208, 176, 106, 076, 020, 019, 017, 014, 012, 003, and 002). CONCLUSION: Ribotypes 027 and 001 were the most frequent C. difficile isolates recovered in this study, and demonstrated higher MICs. Furthermore, we found four isolates with reduced susceptibility to fidaxomicin, raising a concern since this drug is currently unavailable in Mexican Hospitals.


Subject(s)
Clostridioides difficile/genetics , Clostridioides difficile/isolation & purification , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Clostridioides difficile/drug effects , Clostridium Infections/drug therapy , Clostridium Infections/microbiology , Drug Resistance, Bacterial/drug effects , Humans , Mexico , Microbial Sensitivity Tests/methods , Ribotyping/methods , Tertiary Care Centers
13.
PLoS One ; 12(12): e0189768, 2017.
Article in English | MEDLINE | ID: mdl-29261736

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome. METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing. RESULTS: We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time. CONCLUSION: The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors' sample.


Subject(s)
Clostridium Infections/therapy , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Adult , Aged , Aged, 80 and over , Bacteria/genetics , Biodiversity , Clostridium Infections/drug therapy , Demography , Feces/microbiology , Female , Gastrointestinal Microbiome/genetics , Genotype , Humans , Male , Metagenomics , Microbial Sensitivity Tests , Middle Aged , Phylogeny , Principal Component Analysis , RNA, Ribosomal, 16S/genetics , Species Specificity , Tissue Donors , Vancomycin/therapeutic use , Young Adult
14.
Genet Mol Res ; 16(2)2017 May 31.
Article in English | MEDLINE | ID: mdl-28613373

ABSTRACT

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. The progression of the disease depends on several host and viral factors and may result in fulminant hepatitis (very rare), acute hepatitis with spontaneous clearance, and chronic hepatitis B infection. Previous studies demonstrated that variations in the human leukocyte antigen (HLA) class II (HLA-DPB1 and HLA-DQB2 genes) are related to the chronic HBV infection. This study aimed to investigate the association of two single nucleotide polymorphism (SNPs), one in the HLA-DPB1 (rs9277535) and one in the HLA-DQB2 (rs7453920), with chronic hepatitis B infection in a southern Brazilian sample. This case-control study included 260 HBV patients attended in a Specialized Center for Health in Caxias do Sul (Brazil) between 2014 and 2016. The same number of controls (matching for age, gender, and ethnicity) was obtained in a University Hospital in the same city and period. Blood samples were collected and genomic DNA was extracted. Genotyping were performed by real-time Taqman PCR method. Odds ratios with 95% confidence intervals and significance level of 5% (P < 0.05) were calculated. Allele frequencies in the SNP rs9277535 were 72.6% for A and 27.4% for G nucleotides in cases and 75.0% for A and 25.0% for G in controls. Allele frequencies in the SNP rs7453920 were of 25.7% for A and 74.3% for G in cases and 28.8% for A and 71.2% for G in controls. No statistically significant association was found between both SNPs and chronic hepatitis B (P > 0.05).


Subject(s)
HLA-DP beta-Chains/genetics , HLA-DQ Antigens/genetics , Hepatitis B, Chronic/genetics , Polymorphism, Single Nucleotide , Adult , Brazil , Case-Control Studies , Female , Humans , Male , Middle Aged
15.
Genet Mol Res ; 15(4)2016 Dec 19.
Article in English | MEDLINE | ID: mdl-28002595

ABSTRACT

The major pathological hallmark of the systemic sclerosis (SSc) is skin and internal organ fibrosis, which results from normal tissue architecture alterations and extracellular matrix (ECM) protein deposition. ECM components are degraded by matrix metalloproteinases (MMP). Promoter region polymorphisms in MMP genes may influence gene expression, resulting in an imbalance between ECM protein production and degradation. Here, we analyzed MMP1 -1607 1G/2G (rs1799750), MMP3 -1171 5A/6A (rs3025058), and MMP9 -1562 C/T (rs3918242) polymorphisms in relation to susceptibility to SSc and its clinical features. The patient group included 98 individuals with longstanding or recently diagnosed disease, meeting the American College of Rheumatology or LeRoy and Medsger criteria for SSc; the control group included 100 healthy blood donors. All participants were of European descent. Genotyping was performed by polymerase chain reaction followed by restriction digestion. Genotype and allele frequencies of MMP polymorphisms were similar between the two groups. In secondary analyses, significantly higher frequency of 1G/2G genotype from MMP1 polymorphism was observed for patients testing positive for antinuclear autoantibodies (P = 0.007), while 1G/1G genotype was associated with interstitial lung disease development (P = 0.018). The 6A/6A genotype from MMP3 polymorphism was absent in patients with calcinosis (P = 0.011), while the MMP3 5A/5A genotype correlated with the presence of anti-topoisomerase I antibodies (P = 0.009) and reduced diffusing capacity for carbon monoxide (P = 0.024). These results suggest that MMP polymorphisms are not associated with SSc susceptibility, although MMP1 and MMP3 variants are associated with specific SSc clinical and laboratory features.


Subject(s)
Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/genetics , Polymorphism, Single Nucleotide , Scleroderma, Systemic/genetics , Adult , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Promoter Regions, Genetic , Scleroderma, Systemic/pathology
16.
Genet Mol Res ; 15(3)2016 Sep 16.
Article in English | MEDLINE | ID: mdl-27706745

ABSTRACT

The aim of this study was to examine the effect of polymorphisms in the cytochrome P450 (CYP) 2C19 gene (CYP2C19) on the Helicobacter pylori eradication rate in Brazilian patients with functional dyspepsia. Adults diagnosed with functional dyspepsia based on the ROME III criteria and infected with H. pylori were recruited to this study. The patients were subjected to gastrointestinal endoscopy and the H. pylori status was defined when both urease test and histopathology results were negative or positive. The patients were treated with proton pump inhibitor-based triple therapy (omeprazole, amoxicillin, and clarithromycin). CYP2C19*2 and CYP2C19*3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. One hundred and forty-eight patients (81.8% women) with a mean (± SD) age of 46.1 (12.2) years were included in this study. Based on the CYP2C19 genotypes, the patients were classified as homozygous extensive metabolizer (HomEM; 67.6%), heterozygous extensive metabolizer (HetEM; 26.3%), or poor metabolizer (PM; 6.1%). The H. pylori eradication rates in patients with HomEM, HetEM, and PM were 85.0, 89.7, and 100.0% (P = 0.376), respectively. The included study population comprised a high frequency of patients carrying the HomEM genotype. Although the genotypes of CYP2C19 variants were not statistically significant, the results of this study suggest a possible effect of the PM genotype on the efficacy of H. pylori eradication.


Subject(s)
Cytochrome P-450 CYP2C19/genetics , Dyspepsia/genetics , Helicobacter Infections/genetics , Helicobacter pylori/genetics , Adult , Aged , Amoxicillin/administration & dosage , Brazil , Clarithromycin/administration & dosage , Dyspepsia/drug therapy , Dyspepsia/microbiology , Endoscopy, Gastrointestinal , Female , Genotype , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Helicobacter pylori/drug effects , Helicobacter pylori/pathogenicity , Humans , Inactivation, Metabolic/genetics , Male , Middle Aged , Omeprazole/administration & dosage , Polymorphism, Single Nucleotide
17.
Mar Pollut Bull ; 104(1-2): 198-206, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26856646

ABSTRACT

In 2010, severe coral bleaching was observed across the southeastern Caribbean, including the island of Tobago, where coral reefs are subject to sedimentation and high nutrient levels from terrestrial runoff. Here we examine changes in corals' colony size distributions over time (2010-2013), juvenile abundances and sedimentation rates for sites across Tobago following the 2010 bleaching event. The results indicated that since pre-bleaching coral cover was already low due to local factors and past disturbance, the 2010 event affected only particular susceptible species' population size structure and increased the proportion of small sized colonies. The low density of juveniles (mean of 5.4±6.3 juveniles/m(-2)) suggests that Tobago's reefs already experienced limited recruitment, especially of large broadcasting species. The juvenile distribution and the response of individual species to the bleaching event support the notion that Caribbean reefs are becoming dominated by weedy non-framework building taxa which are more resilient to disturbances.


Subject(s)
Anthozoa/physiology , Coral Reefs , Animals , Geologic Sediments/analysis , Population Density , Population Dynamics , Trinidad and Tobago
18.
Toxicol Lett ; 241: 175-83, 2016 Jan 22.
Article in English | MEDLINE | ID: mdl-26621539

ABSTRACT

The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization.


Subject(s)
Antivenins/pharmacology , Elapid Venoms/antagonists & inhibitors , Elapid Venoms/toxicity , Elapidae , Immunoglobulin Fab Fragments/pharmacology , Immunoglobulin G/pharmacology , Neuromuscular Diseases/chemically induced , Neuromuscular Diseases/prevention & control , Neuromuscular Junction/drug effects , Neurotoxins/antagonists & inhibitors , Neurotoxins/toxicity , Animals , Diaphragm/drug effects , In Vitro Techniques , Lethal Dose 50 , Male , Mice , Muscle Contraction/drug effects , Phrenic Nerve/drug effects , Temperature
20.
Biophys J ; 109(5): 936-47, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26331251

ABSTRACT

Polybia-MP1 (MP1) is a bioactive host-defense peptide with known anticancer properties. Its activity is attributed to excess serine (phosphatidylserine (PS)) on the outer leaflet of cancer cells. Recently, higher quantities of phosphatidylethanolamine (PE) were also found at these cells' surface. We investigate the interaction of MP1 with model membranes in the presence and absence of POPS (PS) and DOPE (PE) to understand the role of lipid composition in MP1's anticancer characteristics. Indeed we find that PS lipids significantly enhance the bound concentration of peptide on the membrane by a factor of 7-8. However, through a combination of membrane permeability assays and imaging techniques we find that PE significantly increases the susceptibility of the membrane to disruption by these peptides and causes an order-of-magnitude increase in membrane permeability by facilitating the formation of larger transmembrane pores. Significantly, atomic-force microscopy imaging reveals differences in the pore formation mechanism with and without the presence of PE. Therefore, PS and PE lipids synergistically combine to enhance membrane poration by MP1, implying that the combined enrichment of both these lipids in the outer leaflet of cancer cells is highly significant for MP1's anticancer action. These mechanistic insights could aid development of novel chemotherapeutics that target pathological changes in the lipid composition of cancerous cells.


Subject(s)
Antimicrobial Cationic Peptides/pharmacology , Antineoplastic Agents/pharmacology , Cell Membrane/drug effects , Cell Membrane/metabolism , Phosphatidylethanolamines/metabolism , Phosphatidylserines/metabolism , Wasp Venoms/pharmacology , Cell Membrane/chemistry , Cell Membrane Permeability/drug effects , Dose-Response Relationship, Drug , Kinetics , Porosity/drug effects , Unilamellar Liposomes/chemistry , Unilamellar Liposomes/metabolism
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