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1.
J Stroke Cerebrovasc Dis ; 33(7): 107757, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38705498

RESUMO

BACKGROUND: Current literature lacks guidance on the safety of administering anticoagulation in acute ischemic stroke with emergent indications that require anticoagulation other than atrial fibrillation. Therefore, we tend to rely on studies investigating acute ischemic stroke in atrial fibrillation for anticoagulation recommendations. METHODS: We retrospectively reviewed data for patients with acute ischemic stroke who had a non-atrial fibrillation emergent indication for anticoagulation (e.g., intra-arterial thrombus, intracardiac thrombus, acute coronary syndrome, acute limb ischemia, deep vein thrombosis and pulmonary embolism) diagnosed within 3 days of acute ischemic stroke. Patients who received anticoagulation ≤ 3 days of stroke onset (Group A) were compared to those who either received it afterwards or did not receive it at all (Group B). RESULTS: Out of the 558 patients, only 88 patients met our inclusion criteria. Of the total cohort, 55.7 % patients were males, and basic demographics were similar in both groups except for milder strokes in Group A (national institute of health stroke scale 6 vs. 12.5, p = 0.03). Only 2 patients in Group A and 1 patient in Group B developed intracranial hemorrhage, which was not statistically significant. Group A patients had a lower incidence of both new diagnosis (2 % vs. 34.2 % %, p < 0.001) and propagation of an established venous thromboembolism. They also had a lower rate of any thromboembolic complication (2 % vs. 42 %, p < 0.001). CONCLUSION: Early anticoagulation (i.e., ≤ 3 days) in non-atrial fibrillation ischemic stroke patients with an emergent indication may be safe and carry a lower risk of thromboembolic complications than later anticoagulation.


Assuntos
Anticoagulantes , Esquema de Medicação , AVC Isquêmico , Tempo para o Tratamento , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , AVC Isquêmico/diagnóstico , AVC Isquêmico/etiologia , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/prevenção & controle , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Fatores de Tempo , Pessoa de Meia-Idade , Resultado do Tratamento , Fatores de Risco , Idoso de 80 Anos ou mais , Medição de Risco , Hemorragias Intracranianas/induzido quimicamente
2.
Trop Anim Health Prod ; 55(3): 176, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37099038

RESUMO

This study aimed to determine whether feeding betaine (Bet) to lactating Nili-Ravi buffaloes elevates their production performance during the hot and humid climate. Sixty lactating Nili-Ravi buffaloes were randomly divided into four groups: the control group received a standard concentrates basal diet without Bet, whereas in the treated group the same diet was supplemented with Bet at 0.2%, 0.4%, and 0.6% on dry matter basis for 9 weeks. All animals received ad libitum amount of chopped green maize fodder. Milk production and its fat % were recorded twice daily, whereas for the remaining components samples were collected weekly. Blood samples were collected at the end of the experiment. The results showed that feeding Bet to buffaloes increased (p<0.05) milk yield, production efficiency, and nutrient utilization at all three inclusion levels; however, milk composition remained unaffected. A numerical but non-significant (p>0.05) increase in performance was noticed with higher doses of Bet. Superoxide dismutase in all three treatments and glutathione peroxidase in Bet 0.2% inclusion level were higher (p<0.05) as compared to the control. However, malondialdehyde was not significantly affected. Inclusion of Bet in the concentrate ration of lactating buffalos at 0.2% level on the dry matter basis is recommended as it positively influenced the production and also improved their antioxidant status during summer.


Assuntos
Antioxidantes , Bison , Feminino , Animais , Antioxidantes/farmacologia , Betaína , Búfalos , Lactação , Suplementos Nutricionais
3.
Microb Pathog ; 163: 105389, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34998933

RESUMO

Emergence of multidrug resistance in E. coli and advent of newer strains is becoming serious concern which requires keen observations. This study was designed to find the ciprofloxacin resistant E. coli isolates co-existed with multi-drug resistance along with ß-lactamase production from poultry source, and finally the genome sequencing of these strains to explore genetic variations. Study constituted on isolation of n = 225 E. coli from broiler farms of central China which were further subjected to identification of resistance against ciprofloxacin followed by antibiogram of n = 26 antibiotics and identification of ß-lactamase production. Whole genome resequencing was performed using Illumina HiSeq 4000 system. PCR results revealed predominant ß-lactamase genes i.e.CTX-M, CTX-M-1, CTX-M3, TEM-1 and OXA. Furthermore, the MDR isolates were containing most of the tested virulence genes. The most prevalent virulence genes were pap-C, fim-C, fim-H, iuc-D, irp-2, tra-T, iro-N and iut-A. The single nucleotide polymorphisms (SNPs) loci mentioned in this data give valuable genetic markers to growing high-throughput techniques for fine-determination of genotyping of MDR and virulent isolates. Characterization of SNPs on functional basis shed new bits of knowledge on the evolution, disease transmission and pathogenesis of MDR E. coli isolates. In conclusion, these findings provide evidence that most of poultry E. coli are MDR, ß-lactamase producers, and virulent which could be a zoonotic threat to the humans. The whole genome resequencing data provide higher resolution of resistance and virulence characteristics in E. coli which can further be used for the development of prevention and treatment strategies.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Animais , Antibacterianos/farmacologia , Galinhas , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Infecções por Escherichia coli/veterinária , Humanos , Virulência/genética , beta-Lactamases/genética
4.
Microb Pathog ; 158: 105040, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34119627

RESUMO

Antibiotic-resistant bacteria are considered one of the major global threats to human and animal health. The most harmful among the resistant bacteria are ß-lactamase producing Gram-negative species (ß-lactamases). ß-lactamases constitute a paradigm shift in the evolution of antibiotic resistance. Therefore, it is imperative to present a comprehensive review of the mechanisms responsible for developing antimicrobial resistance. Resistance due to ß-lactamases develops through a variety of mechanisms, and the number of resistant genes are involved that can be transferred between bacteria, mostly via plasmids. Over time, these new molecular-based resistance mechanisms have been progressively disclosed. The present review article provides information on the recent findings regarding the molecular mechanisms of resistance to ß-lactams in Gram-negative bacteria, including CTX-M-type ESBLs with methylase activity, plasmids harbouring phages with ß-lactam resistance genes, the co-presence of ß-lactam resistant genes of unique combinations and the presence of ß-lactam and non-ß-lactam antibiotic-resistant genes in the same bacteria. Keeping in view, the molecular level resistance development, multifactorial and coordinated measures may be taken to counter the challenge of rapidly increasing ß-lactam resistance.


Assuntos
Bactérias Gram-Negativas , Resistência beta-Lactâmica , beta-Lactamases , Bactérias Gram-Negativas/genética , beta-Lactamases/genética , beta-Lactamas/farmacologia
5.
Microb Pathog ; 160: 105201, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34547409

RESUMO

The emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains of animal origin that are resistant to several antibiotics is of great concern. Cefquinome is a fourth-generation cephalosporin developed specifically for veterinary use. The mechanism of MRSA resistance to cefquinome is still not established. Therefore, we designed this study to evaluate the effect of cefquinome on the transcriptome of MRSA1679a, a strain that was isolated from a chicken. The transcriptome analysis indicated that multiple efflux pumps (QacA, NorB, Bcr, and ABCb) were upregulated in MRSA1679a as a resistance mechanism to expel cefquinome. Additionally, penicillin-binding protein 1A was overexpressed, which conferred resistance to cefquinome, a ß-lactam antibiotic. Adhesion and the biofilm-forming capacity of the MRSA strain was also enhanced in addition to overexpression of many stress-related genes. Genes related to carbohydrate metabolism, secretion systems, and transport activity were also significantly upregulated in MRSA1679a. In conclusion, global transcription was triggered to overcome the stress induced by cefquinome, and the MRSA1679a showed a great genetic potential to survive in this challenging environment. This study provides a profound understanding of MRSA1679a as a potentially important pathogen and identifies key resistance characteristics of MRSA against cefquinome. Studies should be aimed to demonstrate multidrug resistance mechanisms of virulent strains by exposing to different antibiotic combinations.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Cefalosporinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , RNA-Seq
6.
Ecotoxicol Environ Saf ; 220: 112333, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34058674

RESUMO

Deoxynivalenol (DON) is considered to be a grave threat to humans and animals. Ginsenoside Rb1 (Rb1) has been reported for its antioxidant potential and medicinal properties. However, the shielding effects of Rb1 and the precise molecular mechanisms against DON-induced immunotoxicity in mice have not been reported yet. In the present research, 4-weeks old healthy C57BL/6 mice were randomly assigned into four experimental groups (n = 12), viz., CON, DON 3 mg/kg BW, Rb1 50 mg/kg BW and DON 3 mg/kg + Rb1 50 mg/kg BW (DON + Rb1). Feed intake and body weight gain were monitored during the entire experiment (15 d). Our results demonstrated that Rb1 markedly increased the ADG (30%) and ADFI (25.10%) of mice compared with DON group. Furthermore, Rb1 alleviated the DON-induced immune injury by relieving the splenic histopathological alteration, enhancing the T-lymphocytes subsets (CD4+, CD8+), the levels of cytokines (IL-2, IL-6, IFN-γ, and TNF-α), as well as production of immunoglobulins (IgA, IgM, and IgG). Moreover, Rb1 ameliorated DON-inflicted oxidative stress by reducing the ROS, MDA and H2O2 contents and boosting the antioxidant defense system (T-AOC, T-SOD, CAT, and GSH-Px). Additionally, Rb1 significantly reversed the DON-induced excessive splenic apoptosis via modulating the mitochondria-mediated apoptosis pathway in mice, depicting the decreased percentage of splenocyte apoptotic cells by 26.65%, down-regulated the mRNA abundance of Bax, caspase-3, caspase-9, and protein expression of Bax, cleaved caspase-3, and Cyt-c. Simultaneously, Rb1 markedly rescued both Bcl-2 mRNA and protein expression levels. Taken together, Rb1 mitigates DON-induced immune injury by suppressing the oxidative damage and regulating the mitochondria-mediated apoptosis pathway in mice. Conclusively, our current research provides an insight into the preventive mechanism of Rb1 against DON-induced immune injury in mice and thus, presents a scientific baseline for the therapeutic application of Rb1.


Assuntos
Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Imunotoxinas/efeitos adversos , Micotoxinas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Tricotecenos/efeitos adversos , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
7.
Molecules ; 26(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067122

RESUMO

Organic materials development, especially in terms of nonlinear optical (NLO) performance, has become progressively more significant owing to their rising and promising applications in potential photonic devices. Organic moieties such as carbazole and quinoline play a vital role in charge transfer applications in optoelectronics. This study reports and characterizes the donor-acceptor-donor-π-acceptor (D-A-D-π-A) configured novel designed compounds, namely, Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1. We further analyze the structure-property relationship between the quinoline-carbazole compounds for which density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed at the B3LYP/6-311G(d,p) level to obtain the optimized geometries, natural bonding orbital (NBO), NLO analysis, electronic properties, and absorption spectra of all mentioned compounds. The computed values of λmax, 364, 360, and 361 nm for Q3, Q4, and Q5 show good agreement of their experimental values: 349, 347, and 323 nm, respectively. The designed compounds (Q3D1-Q5D1) exhibited a smaller energy gap with a maximum redshift than the reference molecules (Q3-Q5), which govern their promising NLO behavior. The NBO evaluation revealed that the extended hyperconjugation stabilizes these systems and caused a promising NLO response. The dipole polarizabilities and hyperpolarizability (ß) values of Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1 exceed those of the reference Q3, Q4, and Q5 molecules. These data suggest that the NLO active compounds, Q3D1-Q3D3, Q4D1-Q1D2, and Q5D1, may find their place in future hi-tech optical devices.

8.
Trop Anim Health Prod ; 53(1): 19, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216230

RESUMO

Sheep farming is the backbone of a rural economy in developing countries, and haemonchosis is a major impediment in the way of its progress. Haemonchus contortus (H. contortus) infection persists all over the world particularly in the tropical and sub-tropical regions. Various review articles have been published to substantially cover one or more aspects of its morphology, prevalence, pathogenesis, symptoms, diagnosis, immune response, drug resistance, treatment, and control measure. The objective of this paper is to briefly review past and present information available in the aforementioned areas in one place to enable the readers to fully understand the problem from a broader perspective. H. contortus parasite harbours in abomasum of affected animal and feeds on its blood, producing mild to severe symptoms and even death in acute form. The parasite thus inflicts heavy production losses and is of economic importance. H. contortus has developed diverse characters over the years leading to limited success in the production of vaccines. Indiscriminate use of the anthelmintics has produced drug resistance against almost all conventional products. Efficacy of medicinal plants and non-conventional chemicals has been reported under controlled experiments; however, research on their adverse effects on growth and fertility is yet to be studied. Research on molecular tools for identification and introduction of resistant genes into the flock is also underway but still a long journey to find its field application. Crossbreeding may compromise the production traits of the existing flock. In given circumstances, a targeted selective treatment approach along with selective breeding, culling of more susceptible animals, and maintaining a good body condition score through the provision of a balanced diet remains a workable strategy to control haemonchosis in sheep.


Assuntos
Hemoncose/veterinária , Haemonchus , Doenças dos Ovinos , Animais , Hemoncose/diagnóstico , Hemoncose/epidemiologia , Hemoncose/terapia , Haemonchus/anatomia & histologia , Haemonchus/fisiologia , Prevalência , Ovinos , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/terapia , Carneiro Doméstico
9.
Z Naturforsch C J Biosci ; 74(1-2): 25-33, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30543521

RESUMO

Previous studies show that certain physical and chemical properties of chemical compounds are closely related with their molecular structure. As a theoretical basis, it provides a new way of thinking by analyzing the molecular structure of the compounds to understand their physical and chemical properties. The molecular topological indices are numerical invariants of a molecular graph and are useful to predict their bioactivity. Among these topological indices, the eccentric-connectivity index has a prominent place, because of its high degree of predictability of pharmaceutical properties. In this article, we compute the closed formulae of eccentric-connectivity-based indices and its corresponding polynomial for water-soluble perylenediimides-cored polyglycerol dendrimers. Furthermore, the edge version of eccentric-connectivity index for a new class of dendrimers is determined. The conclusions we obtained in this article illustrate the promising application prospects in the field of bioinformatics and nanomaterial engineering.


Assuntos
Dendrímeros/química , Modelos Químicos , Imidas/química , Perileno/análogos & derivados , Perileno/química , Solubilidade , Água/química
10.
Regul Toxicol Pharmacol ; 73(1): 201-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26190303

RESUMO

To evaluate the microbiological safety of tilmicosin on human intestinal microflora, four chemostat models of healthy human colonic ecosystems were exposed to tilmicosin (0, 0.436, 4.36, and 43.6 µg/mL) for 7 days. Prior to and during drug exposure, three microbiological endpoints were monitored daily including short-chain fatty acids, bacterial counts and macrolide susceptibility. Colonization resistance of each community was determined by 3 successive daily challenges of Salmonella typhimurium. Genes associated with virulence and macrolide resistance in Enterococcus faecalis were determined by PCR. Transcriptional expression of the virulence gene (gelE) in E. faecalis was determined by real-time RT-PCR. Our results showed that different concentrations of tilmicosin did not disrupt the colonization resistance in each chemostat. During exposure to 4.36 and 43.6 µg/mL tilmicosin, the Bacteroides fragilis population was significantly decreased while the proportion of resistant Enterococci increased. After long-term exposure to the highest concentration (43.6 µg/mL) of tilmicosin, the gelE gene was significantly up-regulated in the high-level macrolide resistant strains that also contained the ermB resistance gene. This study was the first of its kind to evaluate the microbiological toxicity of tilmicosin using a chemostat model. These findings also provide new insight into the co-occurrence of macrolide resistance and virulence in E. faecalis under tilmicosin selective pressure.


Assuntos
Antibacterianos/efeitos adversos , Colo/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Tilosina/análogos & derivados , Bacteroides fragilis/efeitos dos fármacos , Bacteroides fragilis/genética , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Genes Bacterianos/genética , Humanos , Testes de Sensibilidade Microbiana/métodos , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Tilosina/efeitos adversos
12.
J Interv Cardiol ; 27(1): 58-62, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24152197

RESUMO

OBJECTIVES: We evaluated the safety and efficacy of low-dose heparin (40 IU/kg) for elective percutaneous coronary intervention (PCI). BACKGROUND: Current guidelines recommend a 70-100 IU/kg bolus of heparin for elective PCI, but this dose may be associated with increased bleeding risk. Low-dose heparin may have an advantage in this regard, but has not been well studied. METHODS: From January 2008 to October 2012, 300 patients underwent elective transfemoral PCI and were treated with an initial bolus of 40 IU/kg of heparin at the UCLA Medical Center. Dual antiplatelet therapy with clopidogrel and aspirin was administered prior to or just after diagnostic coronary angiography. The primary end-point was the composite of cardiac death, myocardial infarction, urgent target vessel revascularization for ischemia, or major bleeding within 30 days after PCI. RESULTS: The mean activating clotting time was 233 ± 28 seconds. The primary end-point occurred in 2.3%. The cardiac death rate was 0.3% but was not related to the PCI. The myocardial infarction rate was 1.3%. Urgent target vessel revascularization occurred in 1 patient (0.3%). The major bleeding rate was 0.3%. No stent thrombosis occurred. CONCLUSION: Using a lower dose of heparin with dual antiplatelet therapy is safe and is associated with a low bleeding risk after transfemoral PCI while providing suppression of ischemic events. This may also represent a cost savings compared with other antithrombotic strategies. A randomized clinical trial comparing low-dose heparin with bivalirudin in patients is required to determine the optimal anticoagulation strategy.


Assuntos
Anticoagulantes/administração & dosagem , Heparina/administração & dosagem , Intervenção Coronária Percutânea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Res Sq ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38854014

RESUMO

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta peptides within cerebral blood vessels, leading to neurovascular complications. Ischemic strokes result from acute disruptions in cerebral blood flow, triggering metabolic disturbances and neurodegeneration. Both conditions often co-occur and are associated with respiratory dysfunctions. The retrotrapezoid nucleus (RTN), which is crucial for CO2 sensing and breathing regulation in the brainstem, may play a key role in breathing disorders seen in these conditions. This study aims to investigate the role of Transforming Growth Factor Beta (TGF-ß) signaling in the RTN on respiratory and cognitive functions in CAA, both with and without concurrent ischemic stroke. Methods: Adult male Tg-SwDI (CAA model) mice and C57BL/6 wild-type controls underwent stereotaxic injections of lentivirus targeting TGF-ß2R2 in the RTN. Stroke was induced by middle cerebral artery occlusion using a monofilament. Respiratory functions were assessed using whole-body plethysmography, while cognitive functions were evaluated through the Barnes Maze and Novel Object Recognition Test (NORT). Immunohistochemical analysis was conducted to measure TGF-ßR2 and GFAP expressions in the RTN. Results: CAA mice exhibited significant respiratory dysfunctions, including reduced respiratory rates and increased apnea frequency, as well as impaired cognitive performance. TGF-ßR2 knockdown in the RTN improved respiratory functions and cognitive outcomes in CAA mice. In CAA mice with concurrent stroke, TGF-ßR2 knockdown similarly enhanced respiratory and cognitive functions. Immunohistochemistry confirmed reduced TGF-ßR2 and GFAP expressions in the RTN following knockdown. Conclusions: Our findings demonstrate that increased TGF-ß signaling and gliosis in the RTN contribute to respiratory and cognitive dysfunctions in CAA and CAA with stroke. Targeting TGF-ßR2 signaling in the RTN offers a promising therapeutic strategy to mitigate these impairments. This study is the first to report a causal link between brainstem gliosis and both respiratory and cognitive dysfunctions in CAA and stroke models.

14.
Virol J ; 10: 170, 2013 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-23721461

RESUMO

BACKGROUND: Newcastle disease (ND) is one of the most deadly diseases of poultry around the globe. The disease is endemic in Pakistan and recurrent outbreaks are being reported regularly in wild captive, rural and commercial poultry flocks. Though, efforts have been made to characterize the causative agent in some of parts of the country, the genetic nature of strains circulating throughout Pakistan is currently lacking. MATERIAL AND METHODS: To ascertain the genetics of NDV, 452 blood samples were collected from 113 flocks, originating from all the provinces of Pakistan, showing high mortality (30-80%). The samples represented domesticated poultry (broiler, layer and rural) as well as wild captive birds (pigeons, turkeys, pheasants and peacock). Samples were screened with real-time PCR for both matrix and fusion genes (1792 bp), positive samples were subjected to amplification of full fusion gene and subsequent sequencing and phylogenetic analysis. RESULTS: The deduced amino acid sequence of the fusion protein cleavage site indicated the presence of motif (112RK/RQRR↓F117) typical for velogenic strains of NDV. Phylogenetic analysis of hypervariable region of the fusion gene indicated that all the isolates belong to lineage 5 of NDV except isolates collected from Khyber Pakhtunkhwa (KPK) province. A higher resolution of the phylogenetic analysis of lineage 5 showed the distribution of Pakistani NDV strains to 5b. However, the isolates from KPK belonged to lineage 4c; the first report of such lineage from this province. CONCLUSIONS: Taken together, data indicated the prevalence of multiple lineages of NDV in different poultry population including wild captive birds. Such understanding is crucial to underpin the nature of circulating strains of NDV, their potential for interspecies transmission and disease diagnosis and control strategies.


Assuntos
Variação Genética , Doença de Newcastle/epidemiologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/classificação , Vírus da Doença de Newcastle/genética , Animais , Aves , Análise por Conglomerados , Genótipo , Epidemiologia Molecular , Dados de Sequência Molecular , Vírus da Doença de Newcastle/isolamento & purificação , Paquistão/epidemiologia , Filogenia , Aves Domésticas , RNA Viral/genética , Análise de Sequência de DNA , Proteínas Virais de Fusão/genética
15.
Regul Toxicol Pharmacol ; 67(3): 335-43, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23973379

RESUMO

The aim of this study was to evaluate the microbiological safety of cyadox, a new member of quinoxaline-1,4-dioxides (QdNOs), on human intestinal flora. Four chemostats containing human fecal flora were exposed to 0, 16, 32, and 128 µg/mL of cyadox, respectively. Bacterial populations, resistance rates of two predominant bacteria and short-chain fatty acids (SCFA) were monitored daily prior to and during drug MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products exposure. Colonization resistance (CR) of each community was determined by three successive daily challenges of Salmonella typhimurium. Efflux pump gene (oqxAB) in the Escherichia coli and Enterococcus strains were analyzed by PCR amplification and DNA sequencing. No change in SCFA was observed after exposure to different concentrations of cyadox. Lower concentration of cyadox (16 µg/mL) had no adverse effect on human microflora. However, higher concentrations of cyadox (32 and 128 µg/mL) could change bacterial population and increase the proportion of resistant E. coli and Enterococcus. More than 26% (12/46) of cyadox resistant E. coli strains contained oqxAB gene, while all the resistant Enterococcus were negative to oqxAB gene. Relationship between the occurrence of oqxAB gene and cyadox exposure is inconclusive. Our data indicated that 16 µg/mL might be the no observed effect concentration (NOEC) of cyadox. Derived microbiological acceptable daily intake (mADI) would be 1552.03 µg/kg d. The data obtained in present study indicated that cyadox was a safe member of QdNOs family of antimicrobial agents.


Assuntos
Anti-Infecciosos/toxicidade , Colo/microbiologia , Modelos Biológicos , Drogas Veterinárias/toxicidade , Bacteroides fragilis/efeitos dos fármacos , Bacteroides fragilis/genética , Bacteroides fragilis/crescimento & desenvolvimento , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/genética , Bifidobacterium/crescimento & desenvolvimento , Colo/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Enterococcus/efeitos dos fármacos , Enterococcus/genética , Enterococcus/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Fezes/microbiologia , Genes Bacterianos , Humanos , Testes de Sensibilidade Microbiana , Nível de Efeito Adverso não Observado , Quinoxalinas/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Salmonella typhimurium/crescimento & desenvolvimento
16.
Plants (Basel) ; 12(9)2023 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-37176798

RESUMO

The unique properties of NB, such as its nano-size effect and greater adsorption capacity, have the potential to mitigate ammonia (NH3) emission, but may also pose threats to soil life and their associated processes, which are not well understood. We studied the influence of different NB concentrations on NH3 emission, soil microbial biomass, nutrient mineralization, and corn nutrient uptake from farmyard manure (FM). Three different NB concentrations i.e., 12.5 (NB1), 25 (NB2), and 50% (NB3), alone and in a fertilizer mixture with FM, were applied to corn. NB1 alone increased microbial biomass in soil more than control, but other high NB concentrations did not influence these parameters. In fertilizer mixtures, NB2 and NB3 decreased NH3 emission by 25% and 38%, respectively, compared with FM alone. Additionally, NB3 significantly decreased microbial biomass carbon, N, and soil potassium by 34%, 36%, and 14%, respectively, compared with FM. This toxicity to soil parameters resulted in a 21% decrease in corn K uptake from FM. Hence, a high NB concentration causes toxicity to soil microbes, nutrient mineralization, and crop nutrient uptake from the FM. Therefore, this concentration-dependent toxicity of NB to soil microbes and their associated processes should be considered before endorsing NB use in agroecosystems.

17.
Open Forum Infect Dis ; 10(11): ofad518, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37953814

RESUMO

Background: Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety, and preliminary activity of duvelisib, a PI3Kδγ inhibitor, for the treatment of COVID-19 critical illness. Methods: We enrolled adults aged ≥18 years with a primary diagnosis of COVID-19 with hypoxic respiratory failure, shock, and/or new cardiac disease, without improvement after at least 48 hours of corticosteroid. Participants received duvelisib (25 mg) or placebo for up to 10 days. Participants had daily semi-quantitative viral load measurements performed. Dose modifications were protocol driven due to adverse events (AEs) or logarithmic change in viral load. The primary endpoint was 28-day overall survival (OS). Secondary endpoints included hospital and intensive care unit length of stay, 60-day OS, and duration of critical care interventions. Safety endpoints included viral kinetics and AEs. Exploratory endpoints included serial cytokine measurements and cytometric analysis. Results: Fifteen patients were treated in the duvelisib cohort, and 13 in the placebo cohort. OS at 28 days was 67% (95% confidence interval [CI], 38%-88%) compared to 62% (95% CI, 32%-86%) for placebo (P = .544). Sixty-day OS was 60% versus 46%, respectively (hazard ratio, 0.66 [95% CI, .22-1.96]; P = .454). Other secondary outcomes were comparable. Duvelisib was associated with lower inflammatory cytokines. Conclusions: In this pilot study, duvelisib did not significantly improve 28-day OS compared to placebo for severe COVID-19. Duvelisib appeared safe in this critically ill population and was associated with reduction in cytokines implicated in COVID-19 and acute respiratory distress syndrome, supporting further investigation. Clinical Trials Registration: NCT04372602.

18.
Pak J Pharm Sci ; 25(3): 665-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22713959

RESUMO

In this study the effect of paracetamol on pharmacokinetics (PK) of isoniazid (INH) in Teddy goats was investigated. INH was administered as a single oral dose at 10 mg/kg body weight to every experimental goat. After a wash out period of 7 days, INH and paracetamol (at the rate of 15 mg/kg body weight) were given simultaneously through oral route for investigation of drug interactions. Both times, following drug administration, blood samples were collected at predetermined time intervals from the jugular vein of each animal and analyzed for INH by spectrophotometric analysis. PK parameters were calculated using two compartment open model. When used with paracetamol, the value of biological half life (t1/2ß) of INH was significantly decreased (p<0.05) from 2.391 ± 0.216 to 2.17 ± 3.46 hours. The value for apparent volume of distribution (Vd) was also significantly decreased (p<0.05) from 0.905 ± 0.327 to 0.786 ± 0.161 L/kg and total body clearance (CL) was increased insignificantly (p>0.05) from 3.59 ± 2.03 to 4.04 ± 2.61 mL/min/kg. Based on these results, it was concluded that dose of isoniazid should be increased when concomitantly used with paracetamol.


Assuntos
Acetaminofen/farmacologia , Analgésicos não Narcóticos/farmacologia , Antituberculosos/farmacocinética , Isoniazida/farmacocinética , Animais , Interações Medicamentosas , Cabras
19.
Sci Total Environ ; 838(Pt 1): 155965, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35588805

RESUMO

Slow release urea has been widely tested in recent past as an effective method to enhance the crop productivity with fewer environmental concerns. However, very few research studies have been performed using micronutrients as a source of slow release of urea nitrogen. A laboratory and field study were carried out to check the agronomic effects of zinc oxide nanoparticles and its bulk salt coatings on urea prills on wheat (Triticum aestivum L.). Different concentrations of zinc oxide nanoparticles (0.25, 0.5 and 4% elemental zinc) were coated on urea prills to slow down the release rate. Bulk zinc oxide salt (ZnO) with similar concentrations was also used in parallel to make a comparison between nano and bulk salt. The SEM of zinc oxide nanoparticles clearly depicted zinc oxide nanoparticles size within a range of 50-90 nm. The XRD and FTIR spectrums also showed its characteristics peak at designated positions. Field study revealed than 0.5% zinc oxide nanoparticles coated urea boosted the crop growth and yield in comparison to the bulk zinc oxide coated urea having similar zinc concentrations, i.e., 0.25%, 0.5% and 4% elemental zinc. The plant parameters like plant height, root length, root volume, grain yield and dry matter weight were significantly increased due to application of zinc oxide nanoparticles.


Assuntos
Nanopartículas , Oligoelementos , Óxido de Zinco , Fertilizantes/análise , Micronutrientes , Solo , Triticum , Ureia/farmacologia , Zinco/análise , Óxido de Zinco/farmacologia
20.
Front Plant Sci ; 13: 1058219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36733597

RESUMO

Nitrogen (N) losses from conventional fertilizers in agricultural systems are very high, which can lead to serious environmental pollution with economic loss. In this study, innovative slow-release fertilizers were prepared using zinc (Zn) [nanoparticles (NPs) or in bulk], using molasses as an environmentally friendly coating. Several treatments were prepared using Zn in different concentrations (i.e., 0.25%, 0.5%, and 4% elemental Zn). The zinc oxide nanoparticles (ZnO-NPs) were prepared from zinc sulfate heptahydrate (ZnSO4·7H2O), and were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Furthermore, the Zn-loaded urea samples were tested for urea N release rate, leaching of water from soil, and crushing strength to assess the impact of coating on the final finished product. Pot experiments were conducted simultaneously to check the agronomic effects of Zn-coated slow-release urea on the growth and development of wheat (Triticum aestivum L.). The laboratory and pot results confirmed that the ZnO-NP treatments boost wheat growth and yield as a result of reduced N and Zn release. UZnNPs2 (urea coated with 0.5% ZnO-NPs and 5% molasses) demonstrated the best results among all the treatments in terms of slow nutrient release, N and Zn uptake, and grain yield. The UZnNPs2 treatment increased plant yield by 34% (i.e., 4,515 vs. 3,345 kg ha-1) relative to the uncoated prill-treated crop because of the slower release of Zn and N.

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