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INTRODUCTION: Our goal was to investigate the antimicrobial resistance due to beta-lactamase genes and virulent determinants (biofilm-forming ability) expressed by Acinetobacter collected from health settings in Pakistan. A cross-sectional study was conducted for the molecular characterization of carbapenemases and biofilm-producing strains of Acinetobacter spp. METHODOLOGY: Two twenty-three imipenem-resistant Acinetobacter isolates were analyzed from 2020 to 2023.The combination disk test and modified hodge test were performed. Biofilm forming ability was determined by polystyrene tube assay. Multiplex polymerase chain reaction (PCR) for virulent and biofilm-forming genes, and 16S rRNA sequencing were performed. RESULTS: 118 (52.9%) carbapenem-resistant Acinetobacter (CR-AB) were isolated from wounds and pus, 121 (54.2%) from males, and 92 (41.2%) from 26-50-years-olds. More than 80% of strains produced ß-lactamases and carbapenemases. Based on the PCR amplification of the ITS gene, 174 (78.0%) CR-AB strains were identified from CR-Acinetobacter non-baumannii (ANB). Most CR-AB were strong and moderate biofilm producers. Genetic analysis revealed the blaOXA-23, blaTEM, blaCTX-M blaNDM-1 and blaVIM were prevalent in CR-AB with frequencies 91 (94.8%), 68 (70.8%), 19 (19.7%), 53 (55.2%), 2 (2.0%) respectively. Among virulence genes, OmpA was dominant in CR-AB isolates from wound (83, 86.4%), csuE 63 (80.7%) from non-wound specimens and significantly correlated with blaNDM and blaOXA genes. Phylogenetic analysis revealed three different clades for strains based on specimens. CONCLUSIONS: CR-AB was highly prevalent in Pakistan and associated with wound infections. The genes, blaOXA-23, blaTEM, blaCTX-M, and blaNDM-1 were detected in CR-AB. Most CR-AB were strong biofilm producers with virulent genes OmpA and csuE.
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Infecções por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Biofilmes , Carbapenêmicos , beta-Lactamases , Biofilmes/crescimento & desenvolvimento , beta-Lactamases/genética , Humanos , Paquistão , Acinetobacter baumannii/genética , Acinetobacter baumannii/efeitos dos fármacos , Masculino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Feminino , Infecções por Acinetobacter/microbiologia , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana , Adulto Jovem , Proteínas de Bactérias/genética , AdolescenteRESUMO
Aim: The study determines rates of carbapenem resistance (CR) and frequency of blaNDM in multidrug-resistance (MDR) or extensive drug resistance (XDR), and evaluates the potential of phenotypic tests for detecting NDM production. Materials & methods: Singleplex PCR was used to detect blaNDM. Phenotypic tests, including combination disc test (CDST) and modified Hodge test (MHT), were evaluated for NDM production. Results: Among 338 CR isolates, 47.63% were MDR, whereas 52.36% were XDR with 53.25% carrying blaNDM. MHT was found to be discriminative for detecting NDM production, whereas no significant association was observed for CDST. Conclusion: The high incidence of CR and MDR and XDR isolates possessing blaNDM presents an impending threat in therapeutics. Limitations of phenotypic tests suggest better testing, including molecular detection of the enzyme.
[Box: see text].
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Antibacterianos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , beta-Lactamases , beta-Lactamases/genética , beta-Lactamases/metabolismo , Humanos , Paquistão/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
The previous studies have found an association between Big Five personality traits and postpartum depression in women. The present study aimed to find out an association between Big Five personality traits and postpartum depression in a sample of Pakistani fathers. A total of 400 Pakistani fathers who had birth of a child in the past 1 month to 1 year period and had been living with their married partners were recruited purposively by using Google Form based survey from the major cities of Pakistan. The Urdu translated versions of Big Five Personality Inventory (BFI) and Edinburgh Postnatal Depression Scale (EPDS) were used as the main outcome measures to assess the relationship between personality traits and postpartum depression. The results found a significant negative and moderate association between Big Five personality traits and paternal postpartum depression except openness which had a weak association and neuroticism which had a positive and moderate association with PPPD (r(398) = .45). The multiple linear regression analysis found that Big Five personality traits significantly predicted paternal postpartum depression (F(5, 394) = 53.33, p = .001) except openness (B = .007, p = .98). The analysis of variance (ANOVA) found significant differences in paternal postpartum depression for age of father (F(2, 397) = 6.65, p = .001, ηp2 = .03), spouse age (F(2, 393) = 5.97, p = .003, ηp2 = .02), employment type (F(2, 395) = 9.69, p = .001, ηp2 = .04) and time spent at home (F(2, 397) = 6.23, p = .002, ηp2 = .03) while there were found no significant differences for education (F(2, 397) = 1.29, p = .27, ηp2 = .006), marital duration (F(2, 397) = 2.17, p = .11, ηp2 = .01), and birth number of recent child (F(2, 397) = 1.48, p = .22, ηp2 = .007). The study concluded that Big Five personality traits are significantly correlated with and predict paternal postpartum depression except openness which did not predict paternal postpartum depression. The occurrence of paternal postpartum depression varied significantly for age of father, age of spouse, type of employment and time spent at home.
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Depressão Pós-Parto , Pai , Personalidade , Humanos , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Pai/psicologia , Paquistão/epidemiologia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Inventário de PersonalidadeRESUMO
OBJECTIVES: This multicenter study, conducted from a One Health perspective, aimed to comprehensively examine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections and their biofilm-forming capabilities in Pakistan. Phylogenetic analysis of the study isolates was also performed. METHODS: A total of 150 MRSA isolates were screened from various clinical samples using Cefoxitin antibiotic discs. Genotypic confirmation was conducted through mecA, S. aureus-specific nuc, and 16S rRNA genes. Biofilm formation was assessed using Congo red agar (CRA) and slime layer quantification methods. The intercellular adhesion (ica) operon genes, specifically icaA and icaD, were detected. Phylogenetic analysis utilized the 16S rRNA sequences. Statistical associations between various parameters were determined using chi-square analysis. RESULTS: The presence of the mecA gene was observed in 131 out of 150 isolates (87.3%). CRA identified 28% and 40% of isolates as strong and moderate biofilm producers, respectively, while 9.3% were classified as non-biofilm producers. The slime layer assay exhibited higher sensitivity, classifying only 4.7% of isolates as non-biofilm producers. Biofilm-forming genes icaA and icaD were detected in 85.3% and 86.7% of the isolates, respectively. Antibiotic resistance was more prevalent among biofilm-forming isolates, particularly against ciprofloxacin, levofloxacin, erythromycin, trimethoprim-sulfamethoxazole, and fosfomycin. Ceftaroline demonstrated efficacy irrespective of biofilm-forming abilities. Conversely, non-biofilm producers exhibited complete susceptibility to clarithromycin and tigecycline. CONCLUSIONS: Clinical MRSA strains exhibit a substantial potential for biofilm formation, contributing to a resistant phenotype. Routine antibiotic testing in clinical settings that overlook the biofilm aspect may lead to the failure of empiric antibiotic therapy.
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Antibacterianos , Biofilmes , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Paquistão/epidemiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Humanos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/epidemiologia , Antibacterianos/farmacologia , Filogenia , Farmacorresistência Bacteriana , Proteínas de Bactérias/genética , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Cardiovascular comorbidities are believed to cause higher mortality in psoriasis patients. Conversely, systemic therapy may improve overall survival. OBJECTIVE: To evaluate the impact of different comorbidities and therapy on mortality risk of psoriasis patients in the entire population of Alberta, Canada (population 4.37 million). METHODS: Cohorts of psoriasis cases (n = 18,618) and controls (ambulatory patients matched 1:3 by age and sex) were retrieved from Alberta Health Services Data Repository of Reporting database within the period 2012 to 2019. Cases were stratified according to Charlson Comorbidity Index, and the type of therapy. RESULTS: Mortality in psoriasis cohort was significantly higher than in the controls (median age of death 72.0 years vs 74.4 years, respectively). Charlson Comorbidity Index and comorbidities were strong predictors of mortality, in particular drug induced liver injury (hazard ratio 1.8, affective bipolar disease, hazard ratio 1.6, and major cardiovascular diseases. Mortality was lower in patients treated with biologics (hazard ratio 0.54). LIMITATIONS: Some factors (psoriasis type and severity, response to treatment, smoking, alcohol intake) could not be measured. CONCLUSIONS: Hepatic injury, psychiatric affective disorders and cardiovascular disease were major determinants of overall survival in psoriasis. Biologic therapy was associated with a reduced mortality risk.
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Produtos Biológicos , Comorbidade , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/mortalidade , Masculino , Feminino , Estudos de Casos e Controles , Idoso , Pessoa de Meia-Idade , Alberta/epidemiologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Adulto , Idoso de 80 Anos ou maisRESUMO
This study reports the prevalence and antibiotics resistance status of Salmonella detected in raw meat from Lahore, Pakistan. Overall, N = 111 meat samples, were collected from local markets. Salmonella was recovered from 57 (51.35%) samples, including 45.83% of poultry, 60% of buffalo, 64.28% of cow, and 60% of goat meat samples. The predominant Salmonella strains were Salmonella enterica serovars; Typhimurium (45.4%), Typhi (27.2%), and Enteritidis (18.1%), identified by VITEK system and 16S rRNA gene sequencing. The isolates exhibited high resistance to Erythromycin (100%), Cefepime (98.24%), Colistin (94.73%), Azithromycin (92.98%), Tetracycline (87.71%), Polymyxin B (84.21%), Ciprofloxacin (84.21%), Trimethoprim-Sulfamethoxazole (80.70%), Nalidixic Acid (80.70%), Kanamycin (78.94%), Chloramphenicol (77.19%), Streptomycin (71.92%) and Ampicillin (64.91%). While the isolates exhibited more susceptibility to Meropenem (75.43%) and Amikacin (73.68%). N = 8 strains were designated as Multidrug Resistant (MDR) and N = 3 as Extensively Drug-Resistant (XDR) Salmonella. The PCR-based detection of resistance genes revealed the presence of blaTEM-1 gene (100%), catA1 gene (64%), and gyrA gene (18%). The whole genome sequencing (WGS) of two selected strains and subsequent downstream analysis confirmed the strains as MDR and XDR Salmonella enterica serovar Typhi. The study showed that raw meat consumed in Lahore carries a significantly high number of drug-resistant Salmonella.
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Farmacorresistência Bacteriana Múltipla , Salmonella enterica , Animais , Feminino , Bovinos , Prevalência , Paquistão/epidemiologia , RNA Ribossômico 16S , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Salmonella/genética , Carne , Antibacterianos/farmacologia , Salmonella enterica/genéticaRESUMO
BACKGROUND: Ventriculoperitoneal (VP) shunt infections in adults represent a severe complication and make treatment more challenging. Therefore, drug susceptibility patterns are crucial for therapeutic decisions and infection control in neurosurgical centers. This 7-year retrospective study aimed to identify the bacteria responsible for adult VP shunt infections and determine their drug susceptibility patterns. METHODS: This single-center study was performed from 2015 to 2021 in Lahore, Pakistan, and included CSF cultures from VP shunt infections. Demographic data, causative organisms, and antimicrobial susceptibility testing results were collected. Multivariate analysis of variance (MANOVA) and two-sample t-tests were used to analyze and compare the antibiotic sensitivity trends over the study period. RESULTS: 14,473 isolates recovered from 13,937 CSF samples of VP shunt infections were identified and analyzed for their susceptibility patterns to antimicrobials. The proportion of Gram-negative and Gram-positive bacteria were 11,030 (76%) and 3443 (24)%, respectively. The predominant bacteria were Acinetobacter species (n = 5898, 41%), followed by Pseudomonas species (n = 2368, 16%) and coagulase-negative Staphylococcus (CoNS) (n = 1880, 13%). 100% of Staphylococcus aureus (S.aureus) and CoNS were sensitive to vancomycin and linezolid (n = 2580). However, 52% of S. aureus (719/1,343) were methicillin-resistant Staphylococcus aureus (MRSA). Acinetobacter showed maximum sensitivity to meropenem at 69% (2759/4768). Pseudomonas was 80% (1385/1863 sensitive to piperacillin-tazobactam, Escherichia coli (E. coli) showed 72% to amikacin (748/1055), while Klebsiella spp. was 57% (574/1170) sensitive to piperacillin-tazobactam. The sensitivity of piperacillin-tazobactam and meropenem for Gram-negative bacteria decreased significantly (p < 0.05) over 7 years, with 92.2% and 88.91% sensitive in 2015 and 66.7% and 62.8% sensitive in 2021, respectively. CONCLUSION: The significant decrease in the effectiveness of carbapenem and beta-lactam/beta-lactamase inhibitor combination drugs for the common Gram-negative causative agents of VP shunt infections suggests that alternative antibiotics such as colistin, fosfomycin, ceftazidime/avibactam, ceftolozane/tazobactam, and tigecycline should be considered and in consequence included in testing panels. Additionally, it is recommended to adopt care bundles for the prevention of VP shunt infection.
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Infecções Relacionadas à Prótese , Derivação Ventriculoperitoneal , Humanos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Paquistão/epidemiologia , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Derivação Ventriculoperitoneal/efeitos adversos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/epidemiologiaRESUMO
We investigate theoretically the roles of the intrinsic point defects in the photophysics of wide-bandgap multi-quantum-well-structured Cs3Bi2Br9 based on the Shockley-Read-Hall statistics and multiphonon recombination theory. The GW plus Bethe-Salpeter equation calculation reveals that there is a prominent exciton peak below the interband absorption edge, and it clarifies the experimental debate. The most energetically favorable native defects possess deep thermodynamic transition levels. The bromide self-interstitials within the octahedron bilayers exhibit as efficient carrier trapping centers through the non-radiative multiphonon recombination, with a lifetime of 184 ns being on the same order of magnitude as the experimental value. The octahedron bilayer surface bromide self-interstitials account for the experimentally observed dominant blue luminescence in Cs3Bi2Br9. These results reveal that the intrinsic point defects at different sites of the multi-quantum-well-like octahedron bilayers play different roles in the photodynamics of such unique layer-structured semiconductors.
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Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) performs most of the carbon fixation on Earth. However, plant Rubisco is an intrinsically inefficient enzyme given its low carboxylation rate, representing a major limitation to photosynthesis. Replacing endogenous plant Rubisco with a faster Rubisco is anticipated to enhance crop photosynthesis and productivity. However, the requirement of chaperones for Rubisco expression and assembly has obstructed the efficient production of functional foreign Rubisco in chloroplasts. Here, we report the engineering of a Form 1A Rubisco from the proteobacterium Halothiobacillus neapolitanus in Escherichia coli and tobacco (Nicotiana tabacum) chloroplasts without any cognate chaperones. The native tobacco gene encoding Rubisco large subunit was genetically replaced with H. neapolitanus Rubisco (HnRubisco) large and small subunit genes. We show that HnRubisco subunits can form functional L8S8 hexadecamers in tobacco chloroplasts at high efficiency, accounting for â¼40% of the wild-type tobacco Rubisco content. The chloroplast-expressed HnRubisco displayed a â¼2-fold greater carboxylation rate and supported a similar autotrophic growth rate of transgenic plants to that of wild-type in air supplemented with 1% CO2. This study represents a step toward the engineering of a fast and highly active Rubisco in chloroplasts to improve crop photosynthesis and growth.
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Nicotiana , Ribulose-Bifosfato Carboxilase , Nicotiana/metabolismo , Ribulose-Bifosfato Carboxilase/genética , Ribulose-Bifosfato Carboxilase/metabolismo , Fotossíntese/genética , Cloroplastos/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Dióxido de Carbono/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Burn patients are highly susceptible to invasion by multidrug-resistant Gram-negative bacteria (MDR-GNB) through post-burn damage. The prevalence of MDR-GNB isolated from burns patients has increased dramatically in the last decade, representing a serious risk to patients admitted to burns units worldwide. The challenges of managing infected burns patients are exacerbated in poor resource settings. This study was designed to develop a pathway for the rapid diagnosis of multidrug-resistant (MDR) Gram-negative infections and identify the bacterial genes including blaOXA1, blaTEM, and blaSHV encoding ESBLs and blaOXA48, blaKPC, blaNDM, and blaVIM encoding carbapenemases from the patient of post burns infection. METHODS: Clinical isolates were collected (August 2017 to August 2018) from Intensive care unit (ICU) of Burn Centre. Antibiotic susceptibility testing and phenotypic detection of ESBLs and carbapenemases was performed by disk diffusion, double disk synergy test (DDST), combination disk test (CDT), and Imipenem + EDTA combined disk test (IMP + EDTA CDT). Polymerase chain reaction (PCR) detection was performed for ESBLs blaOXA1-blaSHV-blaTEM and carbapenemases genes blaOXA48-blaKPC-blaNDM-blaVIM RESULTS: In total, of 170 Gram-negative isolates, 104 (61.2%) were confirmed as multidrug-resistant (MDR); Pseudomonas aeruginosa was found to be the most prevalent 43/104 (41.4%), followed by Klebsiella pneumoniae 17/104 (16.4%), Acinetobacter baumannii12/104 (11.5%), and 6/104 Proteus mirabilis (5.8%). All isolates (100%) were resistant to cefotaxime and ceftazidime, while the meropenem resistance was 58.7%. ESBL and carbapenemase genotypes were found to be associated with higher MAR index (0.65-0.88) and MIC (> 32 µg/ml) values P. aeruginosa was the major ESBL and carbapenemase producer as determined by phenotypic testing and PCR. blaTEM positive isolates among ESBLs producers were predominant 81.8% (27/33), followed by 27.3% blaOXA1 and blaSHV, respectively. blaVIM positive isolates among carbapenemase producers were predominant 47.7% (21/44), followed by 27.3% blaKPC, 20.5% blaOXA48, and 11.4% blaNDM positive isolates. CONCLUSIONS: The predominant organism causing burn infections was ESBL and carbapenemase-producing Pseudomonas aeruginosa. There are only limited effective antibiotics against such strains. blaVIM and blaTEM individually and in co-existence with blaKPC, blaOXA48, blaSHV, and blaOXA1 confer antimicrobial resistance in burns patients. Rapid detection of ESBL and carbapenemase genes will inform treatment strategies improving the outcome for post-burn patients in ICU.
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Proteínas de Bactérias , beta-Lactamases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Ácido Edético , Bactérias Gram-Negativas/genética , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , beta-Lactamases/genéticaRESUMO
Drought hazard is one of the main consequences of global warming and climate change. Unlike other natural disasters, drought has complex climatic features. Therefore, accurate drought monitoring is a challenging task. This paper proposes a framework for assessing drought classifications at the regional level. The proposed framework provides a new drought monitoring indicator called Multi-Scalar Seasonally Amalgamated Regional Standardized Precipitation Evapotranspiration Index (MSARSPEI). MSARSPEI is an amalgam of the Standardized Precipitation Evapotranspiration (SPEI) (Vicente-Serrano et al., 2010) and Regionally Improved Weighted Standardized Drought Index (RIWSDI) (Jiang et al., 2020). In the proposed framework, the Boruta algorithm of feature selection is configured to ensemble monthly time series data of evaporation in various meteorological stations located in specific regions. Further, the framework suggests the standardization of the Cumulative Distribution Function (CDF) of K-Component Gaussian (K-CG) mixture distribution function for obtaining MSARSPEI data. The application of the proposed framework is based on seven different regions of Pakistan. For comparative analysis, this paper compared the performance of MSARSPE with SPEI using Pearson correlation. Outcomes associated with this research show that the proposed regional drought index has a strong correlation with the competing indicator in various time scales. In addition, the study assessed the spatial extent of various drought classifications under MSARSPEI. In summation, this research concludes that the choice of the MSARSPEI is rationally valid and more appropriate for the regional assessment of drought under the global warming scenario.
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Secas , Aquecimento Global , Mudança Climática , Meteorologia , PaquistãoRESUMO
BACKGROUND: Neonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR. METHODS AND FINDINGS: All studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria. CONCLUSIONS: Gram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.
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Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Sepse Neonatal/tratamento farmacológico , Pobreza , Humanos , Recém-Nascido , Sepse Neonatal/microbiologia , Organização Mundial da SaúdeRESUMO
The aim of the present study was to evaluate the cardioprotective activity of boswellic acids in doxorubicin (DOX) induced cardiotoxicity. DOX (2.5mg/kg) was used intraperitoneally in rats to induce cardiotoxicity in six divided doses every alternate day over a period of two weeks. Dexrazoxane (10:1) was used as a standard drug. Boswellic acids (250, 500 and 750 mg/kg) were orally administered to rats for 14 days. After 14 days, rats were sacrificed, and blood was withdrawn through cardiac puncture. The blood lipid profile and cardiac biomarkers including LDH, CK-MB, CPK, SGOT and troponin T were measured. The heart of rats was isolated for histopathological studies. Graphpad Prism was used for statistical analysis. There was a significant increase in the level of cardiac enzymes and complete lipid profile parameters in diseased group as compared to control group. Pre-treatment with boswellic acids decreased level of all the measured parameters and decreased the severity of myocardial damage as supported by histopathological studies. It was concluded that boswellic acids possess cardioprotective potential by lowering cardiac biomarkers and blood lipid profile. Thus, boswellic acids might act as cardioprotective agent against doxorubicin induced cardiotoxicity.
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Anti-Inflamatórios não Esteroides/farmacologia , Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Coração/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Triterpenos/farmacologia , Animais , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Cardiotoxicidade , Creatina Quinase/efeitos dos fármacos , Creatina Quinase/metabolismo , Creatina Quinase Forma MB/efeitos dos fármacos , Creatina Quinase Forma MB/metabolismo , L-Lactato Desidrogenase/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Infarto do Miocárdio/induzido quimicamente , Miocárdio/metabolismo , Ratos , Troponina T/efeitos dos fármacos , Troponina T/metabolismoRESUMO
BACKGROUND: Polymorphism in the angiotensin-converting enzyme gene (ACE) is responsible for elevated ACE concentrations in plasma. High ACE levels induce insulin resistance and hyperandrogenism, which are the main attributes of polycystic ovary syndrome (PCOS). Therefore, it was hypothesized that I/D polymorphism plays a role in the pathogenesis of PCOS. OBJECTIVE: A case-control study was designed to investigate the association of I/D polymorphism of the ACE gene with PCOS in Pakistani women of reproductive age. METHODS: ACE I/D polymorphism was assessed in 252 women of age group 16-40 years. For genotypic analysis, PCR amplification of genomic DNA was carried out. Statistical analysis was performed to interpret the results using SPSS software. RESULTS: Our study showed that PCOS women were more likely to have a high body mass index and waist circumferences. Most PCOS patients had menstrual irregularities 99.3%, hirsutism 75.2% and cysts in ovaries 66.6%, along with other hyperandrogenic conditions (P-value = 0.001). The genotypic and allelic frequencies were significantly different between patients and controls. There was a significant association of three genotypes with the ratio of LH: FSH among PCOS patients (P = 0.05). Anthropometric characters, comorbidities, clinical symptoms, and PCOS conditions showed no statistical significance with ACE polymorphism. CONCLUSIONS: ACE I/D polymorphism was not found associated with clinical conditions of PCOS in women of reproductive age. However, it was associated with atypical steroidogenesis. So, it indicates that ACE I/D polymorphism aggravates the pathogenesis of PCOS.
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Investigating axonal myelination by Schwann cells (SCs) is crucial for understanding mechanisms underlying demyelination and remyelination, which may help gain insights into incurable disorders like neurodegenerative diseases. In this study, a gelatin-based hydrogel, gelatin methacryloyl (GelMA), was optimized to achieve the biocompatibility, porosity, mechanical stability, and degradability needed to provide high cell viability for dorsal root ganglia (DRG) neurons and SCs, and to enable their long-term coculture needed for myelination studies. The results of cell viability, neurite elongation, SC function and maturation, SC-axon interaction, and myelination were compared with two other commonly used substrates, namely collagen and Poly-d Lysine (PDL). The tuned GelMA constructs (Young's modulus of 32.6 ± 1.9 kPa and the median value of pore size of 10.3 µm) enhanced single axon generation (unlike collagen) and promoted the interaction of DRG neurons and SCs (unlike PDL). While DRG cells exhibited relatively higher viability on PDL after 48 h, i.e., 83.8%, the cells had similar survival rate on GelMA and collagen substrates, 66.7% and 61.5%, respectively. Further adjusting the hydrogel properties to achieve two distinct ranges of relatively small and large pores supported SCs to extend their processes freely and enabled physical contact with and wrapping around their corresponding axons. Staining the cells with myelin basic protein (MBA) and myelin-associated glycoprotein (MAG) revealed enhanced myelination on GelMA hydrogel compared to PDL and collagen. Moreover, the engineered porosity enhanced DRGs and SCs attachments and flexibility of movement across the substrate. This engineered hydrogel structure can now be further explored to model demyelination in neurodegenerative diseases, as well as to study the effects of various compounds on myelin regeneration.
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Gelatina , Hidrogéis , Neurônios , Animais , Células Cultivadas , Colágeno , Gânglios Espinais , Bainha de Mielina , Ratos Sprague-Dawley , Células de SchwannRESUMO
BACKGROUND: Iron deficiency anemia (IDA) is the highest nutritional deficiency worldwide. It is a multifactorial disease, with a higher morbidity rate. TMPRSS6 polymorphisms importantly rs855791 is found to play an essential role in iron homeostasis in the human body. The rs855791 (T > C) polymorphism is highly associated with iron levels, and multiple blood parameters, leading to IDA. The role of TMPRSS6 rs855791 polymorphism and the significance of complete blood count (CBC) parameters in the pathogenesis of IDA is not yet studied in the Pakistani population. METHODS: We enrolled 113 cases and 136 controls to conduct a case control study. Complete blood count (CBC) and iron parameters were analyzed for association studies. PCR-RFLP based genotyping was performed. RESULTS: The TMPRSS6 rs855791 (T > C) polymorphism is significantly associated with IDA pathogenesis as observed in the codominant model and recessive models (P < 0.05, OR: 1.5 and 95% CI: 0.9, 2.6, P < 0.05, OR: 0.5 and 95% CI: 0.2, 0.9 respectively). Elderly women among cases (30-49 years) were found to be more susceptible to IDA (P < 0.05, AOR: 2.1 and 95% CI: 1.0, 4.2). The most significant parameters associated with IDA were red blood cell count (RBC) and hematocrit (Hct%) (P < 0.05, AOR: 16.5, 95% CI: 7.6, 35.9 and P < 0.05, AOR: 10.1, 95% CI: 2.5, 41.6, respectively). CONCLUSION: TMPRSS6 polymorphism at rs855791 (T > C) is significantly associated with IDA susceptibility in reproductive age women in Pakistan. Age, RBC count and Hct% are found to play an important role in IDA pathogenesis in our study population.
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BACKGROUND: Polycystic ovarian syndrome (PCOS) is considered the most common multifactorial endocrinopathy. Genetic factors play an essential role in the pathogenesis of PCOS. CYP 17 enzyme is responsible for androgenesis, while CYP 19 enzyme works for androgen conversion into aromatic estrogen. Several studies have reported their association with PCOS. This study was aimed to investigate the association of cytochrome P450c17α gene (CYP17) 5'-untranslated region MspA1/(rs743572) genetic polymorphism and rs2414096 of cytochrome P450 or aromatase (CYP19) gene polymorphism with the susceptibility to PCOS in reproductive-age women from Punjab, Pakistan. METHODS: We performed a case-control association study was conducted, including 204 PCOS patients and 100 controls. Genotyping of SNP rs2414096 (CYP 19 gene) and P450c17α gene (CYP17) 5'-untranslated region MspA1 was performed on genomic DNA using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis was performed to find out the association of phenotypic and genotypic characters in etiopathology of PCOS. RESULTS: The genotype distribution for CYP 17 5'-UTR MspA1 (TT, TC, CC) revealed that the frequency of genotype TC is significantly higher in PCOS patients (54.9%) vs. controls (OR 4.97, 95% CI 2.75-8.33, p<.001) (12%). The genotype distribution for CYP 19 (GG, GA, AA) showed significantly higher frequency of GA (58.%) and AA (23.5%) in patients as compared to cases (18% and 8%, respectively) (OR 5.49, 95% CI 3.61-8.34, p<.001). Body mass index (BMI), waist, hip, infertility and family history of infertility, PCOS, diabetes, and hypertension were found significantly associated with PCOS. CYP 19 genotypes were found significantly associated with PCOS patients having paraclinical traits of infertility and family history of infertility, while CYP 17 genotypes showed no significant association with any paraclinical traits in PCOS patients. CONCLUSIONS: This is the first study on PCOS genotypes from Pakistan and results suggest that CYP 17 5'-UTR MspA1 (rs743572) (genotype TC) and CYP 19 gene (rs2414096) (genotype GA) polymorphisms are significantly associated with susceptibility to PCOS in Pakistani women having the traits of infertility and family history of hypertension.
Assuntos
Aromatase/genética , Síndrome do Ovário Policístico/genética , Esteroide 17-alfa-Hidroxilase/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Polimorfismo Genético , Adulto JovemRESUMO
INTRODUCTION: Gram-negative bacterial pathogens are associated with complications of post-burn infections that showed significant association with different genotypic variants of extended-spectrum ß-lactamases. In this study, we aimed to determine the distribution of ESBL gene variants among bacterial pathogens from post-burn infections. METHODOLOGY: Cephalosporin-resistant isolates were collected from Jinnah Burn and Reconstructive Surgery Centre, Lahore. Phenotypic testing: double-disk synergy test, combination disk test, multiplex PCR for blaOXA, blaTEM, and blaSHV genes were performed. RESULTS: Of the 53.5% cephalosporin-resistant isolates, 50.7% were community-acquired and 49.3% were nosocomial pathogens. Seventy-two percent of post-burn infections were found in males (p-value = 0.92, OR = 1.04). The age of burn victims ranged from 4 to 85 years (mean = 28.9, SD = 15.6). Pseudomonas aeruginosa was most predominant at a rate of 49%. There were 83.3% multidrug-resistant isolates, which showed susceptibility to meropenem, imipenem, and amikacin in 28.7%, 25.3%, and 26% respectively. In phenotypic tests 16% ESBLs detected by the DDST and 14% confirmed by the CDT. Molecular detection proved effective for the detection of 79.7% blaTEM, 37.7% blaOXA, and 18.8% blaSHV isolates. blaTEM genes were confirmed in 18.1% CDT-positive isolates, with 62.6% diagnostic accuracy (95% CI = 54.7-70) and 88% specificity (95% CI = 80.4-93.4). CONCLUSIONS: The antimicrobial resistance associated with the ESBL-producing Pseudomonas spp. and Enterobacteriaceae is becoming a challenge for the treatment and survival of burn patients. The high rate blaTEM, blaOXA, and blaSHV genes confirm the need to improve the management of burn patients in order to prevent post-burn infections.