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Lipoid proteinosis is a rare multisystem genodermatosis inherited as autosomal recessive trait. We report a case of lipoid proteinosis in a 10-year-old boy born to first-degree consanguineous parents presented with marked hoarseness of voice, accelerated photoaging appearance, enlarged and erythematous tongue with restricted movement and widespread dermatoses. Biopsy of oral mucosa revealed Periodic acid-Schiff (PAS)-positive amorphous eosinophilic hyaline deposits. Mutational analysis revealed a homozygous nonsense mutation with C to T substitution at nucleotide position 1246(c.1246C>T) in exon-8 of the extracellular matrix protein 1 gene leading to a stop codon. Both the parents were unaffected heterozygous carriers. To our knowledge, this is the first case report of lipoid proteinosis with evidence of a novel nonsense genetic mutation from Bangladesh.
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Chloride (Cl-) influences the bioavailability and toxicity of metals in fish, but the mechanisms by which it influences these processes is poorly understood. Here, we investigated the effect of chloride on the cytotoxicity, bioavailability (i.e., accumulation) and bioreactivity (i.e., induction of mRNA levels of metal responsive genes) of copper (Cu) and silver (Ag) in the rainbow trout gut cell line (RTgutGC). Cells were exposed to metals in media with varying Cl- concentrations (0, 1, 5 and 146 mM). Metal speciation in exposure medium was analyzed using Visual MINTEQ software. Cytotoxicity of AgNO3 and CuSO4 was measured based on two endpoints: metabolic activity and membrane integrity. Cells were exposed to 500 nM of AgNO3 and CuSO4 for 24 h in respective media to determine metal bioavailability and bioreactivity. Ag speciation changes from free ionic (Ag+) to neutral (AgCl), to negatively charged chloride complexes (AgCl2-, AgCl3-) with increasing Cl- concentration in exposure media whereas Cu speciation remains in two forms (Cu2+ and CuHPO4) across all media. Chloride does not affect Ag bioavailability but decreases metal toxicity and bioreactivity. Cells exposed to Ag expressed significantly higher metallothionein mRNA levels in low Cl- media (0, 1, and 5 mM) than in high Cl- medium (146 mM). This suggests that chloride complexation reduces silver bioreactivity and toxicity. Conversely, Cu bioavailability and toxicity were higher in the high chloride medium (146 mM) than in the low Cl- (0, 1, and 5 mM) media, supporting the hypothesis that Cu uptake may occur via a chloride dependent mechanism. CLINICAL TRIALS REGISTRATION: This study did not require clinical trial registration.
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Oncorhynchus mykiss , Prata , Animais , Disponibilidade Biológica , Linhagem Celular , Cloretos/toxicidade , Cobre/metabolismo , Cobre/toxicidade , RNA Mensageiro/metabolismo , Prata/metabolismo , Prata/toxicidadeRESUMO
While metals are present in mixture in the environment, metal toxicity studies are usually conducted on an individual metal basis. There is a paucity of data in the existing literature regarding specific metal-metal interactions and their effect on metal toxicity and bioavailability. We studied interactions of a silver (Ag)-copper (Cu) mixture at the intestinal epithelium using an intestinal cell line derived from rainbow trout (Oncorhynchus mykiss), the RTgutGC. Exposures were conducted in media containing different chloride concentrations (low chloride, 1 mM; high chloride, 146 mM), thus resulting in different metal speciation. Cytotoxicity was evaluated based on two endpoints, cell metabolic activity and cell membrane integrity. The Ag-Cu mixture toxicity was assessed using two designs: independent action and concentration addition. Metal mixture bioavailability was studied by exposing cells to 500 nM of Ag or Cu as a single metal or a mixture (i.e., 500 nM of Cu plus 500 nM of Ag). We found an antagonistic effect in the low-chloride medium and an additive/synergistic effect in the high-chloride medium. We found that Cu dominates over Ag toxicity and bioavailability, indicating a competitive inhibition when both metals are present as free metal ions in the exposure media, which supports our hypothesis. Our study also suggests different mechanisms of uptake of free metal ions and metal complexes. The study adds valuable information to our understanding of the role of metal speciation on metal mixture toxicity and bioavailability. Environ Toxicol Chem 2024;43:105-114. © 2023 SETAC.
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Cobre , Oncorhynchus mykiss , Prata , Poluentes Químicos da Água , Animais , Cloretos/química , Cobre/toxicidade , Mucosa Intestinal/metabolismo , Oncorhynchus mykiss/metabolismo , Prata/toxicidade , Poluentes Químicos da Água/toxicidadeRESUMO
The multitude of DNA lesion types, and the nuclear dynamic context in which they occur, present a challenge for genome integrity maintenance as this requires the engagement of different DNA repair pathways. Specific 'repair controllers' that facilitate DNA repair pathway crosstalk between double strand break (DSB) repair and base excision repair (BER), and regulate BER protein trafficking at lesion sites, have yet to be identified. We find that DNA polymerase ß (Polß), crucial for BER, is ubiquitylated in a BER complex-dependent manner by TRIP12, an E3 ligase that partners with UBR5 and restrains DSB repair signaling. Here we find that, TRIP12, but not UBR5, controls cellular levels and chromatin loading of Polß. Required for Polß foci formation, TRIP12 regulates Polß involvement after DNA damage. Notably, excessive TRIP12-mediated shuttling of Polß affects DSB formation and radiation sensitivity, underscoring its precedence for BER. We conclude that the herein discovered trafficking function at the nexus of DNA repair signaling pathways, towards Polß-directed BER, optimizes DNA repair pathway choice at complex lesion sites.
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Salinity variations are the main reason for rice yield fluctuations in salt-prone regions throughout the dry season (Boro season). Plant breeders must produce new rice varieties that are more productive, salt tolerant, and stable across a variety of settings to ensure Bangladesh's food sustainability. To assess the yield and stability, we used fifteen rice genotypes containing two tolerant checks BRRI dhan67, Binadhan-10 and the popular Boro rice variety BRRI dhan28 in different salinity "hotspot" in three successive years followed by additive main effects and multiplicative interaction (AMMI) model utilizing a randomized complete block (RCB) design with two replications. Parents selection was done based on estimated breeding values (EBVs). Eight parents with high EBVs (IR83484-3-B-7-1-1-1, IR87870-6-1-1-1-1-B, BR8992-B-18-2-26, HHZ5-DT20-DT2-DT1, HHZ12-SAL2-Y3-Y2, BR8980-B-1-3-5, BRRI dhan67, and Binadhan-10) might be used to develop new segregating breeding materials. Based on farmer preferences and grain acceptability, three genotypes (IR83484-3-B-7-1-1-1, HHZ5-DT20-DT2-DT1, and HHZ12-SAL2-Y3-Y2) were the winning and best ones. The above three genotypes in the proposed variety trial showed significantly higher yields than the respective check varieties, high salinity tolerance ability, and good grain quality parameters. Among them, HHZ5-DT20-DT2-DT1 and IR83484-3-B-7-1-1-1 harbored eight and four QTL/genes that regulate the valuable traits revealed through 20 SNP genotyping. Finally, two genotypes IR83484-3-B-7-1-1-1 and HHZ5-DT20-DT2-DT1 were released as high salinity-tolerant rice varieties BRRI dhan97 and BRRI dhan99, respectively in Bangladesh for commercial cultivation for sustaining food security and sustainability.
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Oryza , Oryza/genética , Bangladesh , Melhoramento Vegetal , Fenótipo , ClimaRESUMO
Background: Early detection of post-COVID-19-related lung fibrosis is very important for the early introduction of treatment and to minimize morbidity and mortality. The aim of this study is the early detection and evaluation of post-COVID-19 fibrosis by high-resolution computed tomography (HRCT). Methods: This prospective study included 115 patients irrespective of age and sex, who tested positive for the SARS-CoV-2 by nasopharyngeal swab (RT PCR), admitted to the Dhaka North City Corporation (DNCC) dedicated COVID-19 hospital, Dhaka, and discharged after recovery. Patients went through a chest HRCT scan at least once during their hospital stay and another scan during follow-up after hospital discharge and 8 to 12 weeks of negative RT-PCR report. Result: Among 100 patients 23 patients had >50% of total lung involvement by visual assessment. Thirty-three patients had 25% to 50% of total lung volume involvement. Twenty-seven patients had less than 25% of total lung involvement, whereas 17 patients had no visual fibrotic change on the follow-up HRCT scan. A statistical association was found between age, gender, smoking, and severe form of lung fibrosis (P < .05). Patients with mild CT severity score (⩽8) had a very good prognosis. Patients who were admitted to the hospital for more than 15 days were more prone to developing moderate and severe forms of fibrosis. Patients who received at least 2 doses of the COVID-19 vaccine had less severe forms of fibrosis as well as more cases of complete radiological recovery. On the HRCT scan, most of the patients had bilateral, peripheral (68%), and predominant mid & lower lobar parenchymal involvement. Conclusion: Early detection and HRCT evaluation of post-COVID-19 related lung fibrosis is very crucial for early management and introduction of anti-fibrotic drugs.
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The study of nutraceuticals and their connection to immunity is an expanding field of research. The use of nutraceuticals to alleviate stress and enhance immunity in adverse aquaculture environments have been examined to a certain extent. To elucidate the understanding, we focused on the immunological effect of membrane-separated 13% anthocyanin standardized elderberry (EB) extract with maltodextrin excipient, widely used first-line nutraceuticals to augment the immunity, in aquaculture fish, Nile tilapia. To evaluate the potential of EB-extract, we assessed their capability to enhance lymphocyte proliferation and interleukin-2 production in an in-vitro condition using spleen and thymus lymphocytes. The experiments on spleen and thymus T-cells demonstrated significantly higher T-cell proliferation by EB-extract when lectin mitogen Con A was present as a stimulator. Likewise, our spleen B-cell proliferation result reveals a significant effect of EB-extracts, along with B-cell stimulator non-lectin mitogen LPS. Further, the quantification of IL-2 indicates elevated IL-2 levels when spleen T-cells were cultured with EB-extracts and with Con A present as a stimulator. These suggest that 13% anthocyanin standardized EB-extracts can aggrandize fish cells' cellular and humoral immune responses. With further research, elderberry extracts could be used to supplement commercial feed in aquaculture to reduce stress and stimulate the immune response.
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Ciclídeos , Doenças dos Peixes , Sambucus nigra , Sambucus , Animais , Antocianinas/farmacologia , Mitógenos , Interleucina-2 , Suplementos Nutricionais , Extratos Vegetais/farmacologia , Ração Animal/análise , DietaRESUMO
INTRODUCTION: Prominently accountable for the upsurge of COVID-19 cases as the world attempts to recover from the previous two waves, Omicron has further threatened the conventional therapeutic approaches. The lack of extensive research regarding Omicron has raised the need to establish correlations to understand this variant by structural comparisons. Here, we evaluate, correlate, and compare its genomic sequences through an immunoinformatic approach to understand its epidemiological characteristics and responses to existing drugs. METHODS: We reconstructed the phylogenetic tree and compared the mutational spectrum. We analyzed the mutations that occurred in the Omicron variant and correlated how these mutations affect infectivity and pathogenicity. Then, we studied how mutations in the receptor-binding domain affect its interaction with host factors through molecular docking. Finally, we evaluated the drug efficacy against the main protease of the Omicron through molecular docking and validated the docking results with molecular dynamics simulation. RESULTS: Phylogenetic and mutational analysis revealed the Omicron variant is similar to the highly infectious B.1.620 variant, while mutations within the prominent proteins are hypothesized to alter its pathogenicity. Moreover, docking evaluations revealed significant differences in binding affinity with human receptors, angiotensin-converting enzyme 2 and NRP1. Surprisingly, most of the tested drugs were proven to be effective. Nirmatrelvir, 13b, and Lopinavir displayed increased effectiveness against Omicron. CONCLUSION: Omicron variant may be originated from the highly infectious B.1.620 variant, while it was less pathogenic due to the mutations in the prominent proteins. Nirmatrelvir, 13b, and Lopinavir would be the most effective, compared to other promising drugs that were proven effective.
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Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Interações Hospedeiro-Patógeno/genética , Humanos , Lopinavir , Simulação de Acoplamento Molecular , Filogenia , SARS-CoV-2/genética , Virulência/genéticaRESUMO
Assembly and disassembly of DNA repair protein complexes at DNA damage sites are essential for maintaining genomic integrity. Investigating factors coordinating assembly of the base excision repair (BER) proteins DNA polymerase ß (Polß) and XRCC1 to DNA lesion sites identifies a role for Polß in regulating XRCC1 disassembly from DNA repair complexes and, conversely, demonstrates Polß's dependence on XRCC1 for complex assembly. LivePAR, a genetically encoded probe for live-cell imaging of poly(ADP-ribose) (PAR), reveals that Polß and XRCC1 require PAR for repair-complex assembly, with PARP1 and PARP2 playing unique roles in complex dynamics. Further, BER complex assembly is modulated by attenuation/augmentation of NAD+ biosynthesis. Finally, SIRT6 does not modulate PARP1 or PARP2 activation but does regulate XRCC1 recruitment, leading to diminished Polß abundance at sites of DNA damage. These findings highlight coordinated yet independent roles for PARP1, PARP2, and SIRT6 and their regulation by NAD+ bioavailability to facilitate BER.
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Quebras de DNA de Cadeia Simples , Reparo do DNA , DNA de Neoplasias/metabolismo , NAD/metabolismo , Neoplasias/enzimologia , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Sirtuínas/metabolismo , Células A549 , DNA Polimerase beta/genética , DNA Polimerase beta/metabolismo , DNA de Neoplasias/genética , Humanos , Cinética , Microscopia Confocal , Neoplasias/genética , Neoplasias/patologia , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerases/genética , Sirtuínas/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/metabolismoRESUMO
The internet has become an essential part of our daily life. But excessive usage can have a negative impact on the physical health of its users. Over the last decade, the use of Social Media (Facebook) has been increasing rapidly and the younger generations getting addicted to it. But all possible health impacts of excessive use of internet are yet to be thoroughly evaluated, especially in such a developing country as Bangladesh. The present study aims to understand possible health deteriorations from excessive use of Facebook in a cohort of university students of Bangladesh. A cross-sectional study was conducted on 1186 students from two public universities and 1472 from several private universities of Bangladesh using a comprehensive questionnaire. The data were analyzed using the chi-square test to understand the association between Facebook usage behaviors and physical health status. We found that ~70% of the students used the internet for at least 4-6 hours/day, and ~27% of them used Facebook for >3 hrs. Students frequently use social media (mostly Facebook) for news and social communication. About 50% of the students reported wasting time on Facebook and going to sleep late because of it. Importantly, 47.3% students reported that excessive use of Facebook results sleeping disturbance and has a negative impact on the concentration of daily works/studies (p < 0.001). In addition, they experienced several other health problems, including worsening eyesight (71.2%), headaches (15.4%), back and neck pain (28%). Although not statistically important, a fair number of students sought medical attention due to the daily excessive use of internet (p-value = 0.112). These findings demands better understanding of the all possible impacts of using excessive internet among the University students, which can help take the necessary initiatives to encourage good use of the internet. Further extension of this study is suggested at all education levels to reveal the full scenario of degree of excessive internet use and its impact on the healths of Bangladeshi students.
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Elevated expression of the DNA damage response proteins PARP1 and poly(ADP-ribose) glycohydrolase (PARG) in glioma stem cells (GSCs) suggests that glioma may be a unique target for PARG inhibitors (PARGi). While PARGi-induced cell death is achieved when combined with ionizing radiation, as a single agent PARG inhibitors appear to be mostly cytostatic. Supplementation with the NAD+ precursor dihydronicotinamide riboside (NRH) rapidly increased NAD+ levels in GSCs and glioma cells, inducing PARP1 activation and mild suppression of replication fork progression. Administration of NRH+PARGi triggers hyperaccumulation of poly(ADP-ribose) (PAR), intra S-phase arrest and apoptosis in GSCs but minimal PAR induction or cytotoxicity in normal astrocytes. PAR accumulation is regulated by select PARP1- and PAR-interacting proteins. The involvement of XRCC1 highlights the base excision repair pathway in responding to replication stress while enhanced interaction of PARP1 with PCNA, RPA and ORC2 upon PAR accumulation implicates replication associated PARP1 activation and assembly with pre-replication complex proteins upon initiation of replication arrest, the intra S-phase checkpoint and the onset of apoptosis.
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Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs may regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). Accordingly, potent, and selective inhibitors of key ALDH enzymes may represent a novel CSC-directed treatment paradigm for ALDH+ cancer types. Of the many ALDH isoforms, we and others have implicated the elevated expression of ALDH1A3 in mesenchymal glioma stem cells (MES GSCs) as a target for the development of novel therapeutics. To this end, our structure of human ALDH1A3 combined with in silico modeling identifies a selective, active-site inhibitor of ALDH1A3. The lead compound, MCI-INI-3, is a selective competitive inhibitor of human ALDH1A3 and shows poor inhibitory effect on the structurally related isoform ALDH1A1. Mass spectrometry-based cellular thermal shift analysis reveals that ALDH1A3 is the primary binding protein for MCI-INI-3 in MES GSC lysates. The inhibitory effect of MCI-INI-3 on retinoic acid biosynthesis is comparable with that of ALDH1A3 knockout, suggesting that effective inhibition of ALDH1A3 is achieved with MCI-INI-3. Further development is warranted to characterize the role of ALDH1A3 and retinoic acid biosynthesis in glioma stem cell growth and differentiation.
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Aldeído Oxirredutases/antagonistas & inibidores , Glioma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Tretinoína/metabolismo , HumanosRESUMO
The role of metal speciation on metal bioavailability, bio-reactivity and toxicity at the fish intestine is poorly understood. To investigate these processes, we used an in vitro model of the rainbow trout (Oncorhynchus mykiss) intestine, the RTgutGC cell line. Cells were exposed to two essential metals (copper and zinc) and two non-essential metals (cadmium and silver) in a medium of well-defined composition, which allowed the determination of metal speciation in solution. Concentrations resulting in a 50% cell viability reduction (EC50) were measured using a viability assay based on two endpoints: metabolic activity and membrane integrity. Metal bioavailability and bio-reactivity was studied at non-toxic (300 nM all metals) and toxic (EC10; Ag-0.6, Cu-0.9, Cd-3, and Zn-9 µM) concentrations. Bioavailability (i.e. intracellular metal accumulation) was determined by ICP-MS, while bio-reactivity (i.e. induction of a metal specific transcriptional response) was determined by measuring the mRNA levels of a known biomarker of metal exposure (i.e. metallothionein) and of copper and zinc transporters (i.e. ATP7A and ZnT1). Dominant metal species in the exposure medium were Zn2+, CuHPO4, CdCl+, and AgCl2- respectively for Zn, Cu, Cd, and Ag. The EC50s showed the metal toxicity hierarchy: Ag > Cu > Cd > Zn. In RTgutGC cells, essential metal homeostasis was tightly regulated while non-essential metals accumulated more readily. Non-essential metals were also more bio-reactive inducing higher MT and ZnT1 mRNA levels. Taken together these findings indicate that metal toxicity in RTgutGC cannot solely be explained by extracellular metal speciation but requires the evaluation of metal bioavailability and bio-reactivity.
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Cádmio/toxicidade , Cobre/toxicidade , Oncorhynchus mykiss/fisiologia , Prata/toxicidade , Zinco/toxicidade , Animais , Disponibilidade Biológica , Cádmio/farmacocinética , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Células Cultivadas , Cobre/farmacocinética , ATPases Transportadoras de Cobre/genética , ATPases Transportadoras de Cobre/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Metalotioneína/genética , Metalotioneína/metabolismo , Prata/metabolismo , Zinco/farmacocinéticaRESUMO
Inflammatory cytokines are highly inducible small glycoproteins or regulatory proteins of low molecular weight secreted by different cell types. They regulate intercellular communication and mediate a number of physiological functions in the human immune system. Numerous prospective studies report that inflammatory cytokines strongly predict coronary artery disease, myocardial infarction, heart failure and other adverse cardiac events. Inflammatory cascade is believed to be a causative factor in the development of atherosclerotic process. Several aspects of atherogenesis are accelerated by cytokines. This article provides an overall overview of current understanding of cytokines in various cardiovascular events. Besides, inflammatory cytokines trigger cellular events that can induce malignancy and carcinogenesis. Elevated expression of several cytokines such as interleukin-1, interleukin-6, interleukin-10, tumor necrosis factor-α, macrophage migration inhibitory factor and transforming growth factor-ß are involved in tumor initiation and progression. Thus, they exert a pivotal role in cancer pathogenesis. This review highlights the role of several cytokines in various events of tumorigenesis. Actually, this article summarizes the contributions of cytokines in the pathogenesis of cardiovascular disease and cancer.
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Generally female individuals are more prone to obesity due to their lifestyle and physiology. However, female individuals have got little attention in this aspect. This pioneering study designed to find the level of serum malondialdehyde (MDA), non-enzymatic antioxidant (vitamin C), other trace elements (zinc and iron), and macro-minerals (sodium, potassium, and calcium) for female obesity determining its role and action in disease diagnosis along with propagation. For this prospective case-control study, 70 female obese and 70 healthy individuals were evaluated. Serum lipid peroxidation product malondialdehyde (MDA) concentration was measured to determine the level of lipid peroxidation. UV spectrophotometric method was implemented for vitamin C concentration to measure serum ascorbic acid. Atomic absorption spectroscopy (AAS) was implemented to determine serum macro-minerals (Na, K, and Ca), and trace elements (Zn and Fe) were estimated. For statistical analysis, student's t-test and Pearson's correlation test were executed. A significantly higher concentration of serum MDA (p < 0.001) and low concentration of antioxidants (vitamin C) (p < 0.001) are observed in patient than control group. We found a lower concentration of trace elements (zinc, iron) and macro-minerals (sodium, potassium, and calcium) in patients compared to control except sodium. The mean concentrations for serum Zn, Fe, Na, K, and Ca were 0.34 ± 0.01, 0.25 ± 0.01, 3828.91 ± 205.09, 90.42 ± 6.45, and 43.04 ± 2.38 mg/L and 0.78 ± 0.08, 0.84 ± 0.08, 2600.97 ± 99.79, 223.79 ± 14.64, and 86.43 ± 2.78 mg/L, respectively, for female obese patients and control subjects (p < 0.001). We can suggest from our study that there is a strong association of female obesity with increased serum concentrations of MDA and reduced non-enzymatic antioxidant vitamin C and different serum trace metals and macro-minerals.
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Oligoelementos , Estudos de Casos e Controles , Feminino , Humanos , Minerais , Obesidade , Estresse Oxidativo , Estudos ProspectivosRESUMO
BACKGROUND: Leishmania donovani (L. donovani) is one of the parasites that cause leishmaniasis. The mechanisms by which L. donovani fights against adverse environment and becomes resistant to drugs are not well understood yet. OBJECTIVE: The present study was designed to evaluate the effects of different regulators on the modulation of Transplasma Membrane Electron Transport (transPMET) systems of susceptible and resistant L. donovani cells. MATERIALS AND METHODS: Effects of UV, different buffers, and electron transport inhibitors and stimulators on the reduction of α-lipoic acid (ALA), 1,2-naphthoquinone-4-sulphonic acid (NQSA) and ferricyanide were determined. RESULTS AND DISCUSSION: ALA reductions were inhibited in susceptible, sodium antimony gluconate (SAG)-resistant and paromomycin (PMM)-resistant AG83 amastigote cells, and stimulated in susceptible and SAG-resistant AG83 promastigote cells upon UV exposure. The results indicate that UV irradiation almost oppositely affect ALA reductions in amastigotes and promastigotes. ALA reductions were stimulated in sensitive and inhibited in resistant GE1 amastigotes upon UV exposure. Susceptible amastigotes and promastigotes inhibited, and resistant amastigotes and promastigotes stimulated NQSA reduction under UV irradiation. Thus, susceptible and drug-resistant amastigotes and promastigotes are different in the reduction of ALA. Susceptible and resistant AG83 amastigotes and promastigotes inhibited the ferricyanide reductions upon UV exposure, which indicates, there is no such difference in ferricyanide reductions among susceptible as well as resistant AG83 amastigotes and promastigotes. The reductions of extracellular electron excerptors in susceptible promastigotes requires the availability of Na+ and Cl- ions for maximal activity but susceptible amastigotes are mostly not dependent on the availability of Na+ and Cl- ions. Both in promastigotes and amastigotes, reductions of electron acceptors were strongly inhibited by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone. Furthermore, antimycin A, rotenone and capsaicin markedly inhibited the reductions of electron acceptors in promastigotes, but not in amastigotes. CONCLUSION: Results of this study suggest that the transPMET system is functionally different in wild and resistant strains of L. donovani.
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Resistência a Medicamentos , Transporte de Elétrons , Leishmania donovani/fisiologia , Ferricianetos , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/efeitos da radiação , Estágios do Ciclo de Vida , Naftoquinonas/farmacologia , Oxirredução , Paromomicina/farmacologia , Ácidos Sulfônicos/farmacologia , Ácido Tióctico/metabolismo , Raios UltravioletaRESUMO
BACKGROUND: The present study covered an assessment of methanolic acetate fractions of Pistia stratiotes, commonly known as water lettuce, for analgesic, anti-inflammatory, and CNS depressant activities. METHODS: The methanol acetate fractions were extracted from Pistia stratiotes and administered to the experimental animals as 200 and 400 mg/kg doses to determine the effect on acetic acid-induced writhing and formalin-induced licking and biting, for the assessment of analgesic activity. The anti-inflammatory assay was done using the carrageenan-induced hind paw edema method, while assessment of CNS depressant activity was done using the open field and hole cross tests. The effects were compared to standard reference drugs. RESULTS: At both doses (200 and 400 mg/kg body weight), the methanolic acetate extract of P. stratiotes showed significant analgesic action (P < 0.05) against acetic acid-induced writhing. The extract was also found to give significant protection against licking and biting at both doses. The methanolic acetate extract of P. stratiotes showed a significant (P < 0.05) anti-inflammatory effect from 0 minutes up to 3 hours in the carrageenan-induced paw edema test. In the CNS depressant assay, the methanolic acetate extract showed significant (P < 0.05) depressant activity at both doses from 30 to 120 minutes in both the hole cross and open field tests. CONCLUSION: Thus we can conclude that P. stratiotes extracts have significant analgesic, anti-inflammatory, and CNS depressant activity, compared to standard compounds, in an animal model.
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BACKGROUND: Early diagnosis and appropriate therapy of sepsis is a daily challenge in intensive care units (ICUs) despite the advances in critical care medicine. Procalcitonin (PCT); an innovative laboratory marker, has been recently proven valuable worldwide in this regard. OBJECTIVES: This study was undertaken to evaluate the utility of PCT in a resource constrained country like ours when compared to the traditional inflammatory markers like C - reactive protein (CRP) to introduce PCT as a routine biochemical tool in regional hospitals. MATERIALS AND METHODS: PCT and CRP were simultaneously measured and compared in 73 medico-surgical ICU patients according to the American College of Chest Physicians (ACCP) criteria based study groups. RESULTS: The clinical presentation of 75% cases revealed a range of systemic inflammatory responses (SIRS). The diagnostic accuracy of PCT was higher (75%) with greater specificity (72%), sensitivity (76%), positive and negative predictive values (89% and 50%), positive likelihood ratio (2.75) as well as the smaller negative likelihood ratio (0.33). Both serum PCT and CRP values in cases with sepsis, severe sepsis and septic shock were significantly higher from that of the cases with SIRS and no SIRS (P < 0.01). CONCLUSION: PCT is found to be superior to CRP in terms of accuracy in identification and to assess the severity of sepsis even though both markers cannot be used in differentiating infectious from noninfectious clinical syndrome.
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The non-carcinogenic and carcinogenic risk of arsenic and lead to adults and children via daily dietary intake of food composites in Bangladesh was estimated. The target hazard quotients (THQs), hazard index (HI) and target carcinogenic risk (TR) were calculated to evaluate the non-carcinogenic and carcinogenic health risk from arsenic and lead. Most of the individual food composites contain a considerable amount of arsenic and lead. The highest mean concentrations of arsenic were found in cereals (0.254 mg kg⻹ fw) and vegetables (0.250 mg kg⻹ fw), and lead in vegetables (0.714 mg kg⻹ fw) and fish (0.326 mg kg⻹ fw). The results showed the highest THQs of arsenic in cereals and lead in vegetables for both adults and children which exceeded the safe limit (> 1) indicating that cereals and vegetables are the main food items contributing to the potential health risk. The estimated TR from ingesting dietary arsenic and lead from most of the foods exceeded 10â»6, indicating carcinogenic risks for all adult people of the study area.
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Arsênio/toxicidade , Dieta/efeitos adversos , Poluentes Ambientais/toxicidade , Contaminação de Alimentos , Chumbo/toxicidade , Adulto , Animais , Arsênio/análise , Bangladesh , Carcinógenos Ambientais/análise , Carcinógenos Ambientais/toxicidade , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Países em Desenvolvimento , Dieta/etnologia , Inquéritos sobre Dietas , Grão Comestível/química , Grão Comestível/economia , Poluentes Ambientais/análise , Peixes , Análise de Alimentos , Humanos , Chumbo/análise , Alimentos Marinhos/análise , Alimentos Marinhos/economia , Verduras/química , Verduras/economia , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Simplified cultivation technologies for rice have become increasingly attractive in recent years in China because of their social, economical and environmental benefits. To date, several simplified cultivation technologies, such as conventional tillage and seedling throwing (CTST), conventional tillage and direct seeding (CTDS), no-tillage and seedling throwing (NTST), no-tillage and direct seeding (NTDS) and no-tillage and transplanting (NTTP), have been developed in China. Most studies have shown that rice grown under each of these simplified cultivation technologies can produce a grain yield equal to or higher than traditional cultivation (conventional tillage and transplanting). Studies that have described the influences of agronomic practices on yield formation of rice under simplified cultivation have demonstrated that optimizing agronomy practices would increase the efficiencies of simplified cultivation systems. Further research is needed to optimize the management strategies for CTST, CTDS and NTST rice which have developed quickly in recent years, to strengthen basic research for those simplified cultivation technologies that are rarely used at present (such as NTTP and NTDS), to select and breed cultivars suitable for simplified cultivation and to compare the practicability and effectiveness of different simplified cultivation technologies in different rice production regions.