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1.
Open Vet J ; 14(1): 416-427, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38633182

RESUMO

Background: Acute lung injury (ALI) is a severe condition distinguished by inflammation and impaired gas exchange in the lungs. Staphylococcus aureus, a common bacterium, can cause ALI through its virulence factors. Aloe vera is a medicinal plant that has been traditionally used to treat a variety of illnesses due to its anti-inflammatory properties. Chitosan nanoparticles are biocompatible and totally biodegradable materials that have shown potential in drug delivery systems. Aim: To explore the antibacterial activity of Aloe vera-loaded chitosan nanoparticles (AV-CS-NPs) against S. aureus in vitro and in vivo with advanced techniques. Methods: The antibacterial efficacy of AV-CS-NPs was evaluated through a broth microdilution assay. In addition, the impact of AV-CS-NPs on S. aureus-induced ALI in rats was examined by analyzing the expression of genes linked to inflammation, oxidative stress, and apoptosis. Furthermore, rat lung tissue was scanned histologically. The rats were divided into three groups: control, ALI, and treatment with AV-CS-NPs. Results: The AV-CS-NPs that were prepared exhibited clustered semispherical and spherical forms, having an average particle size of approximately 60 nm. These nanoparticles displayed a diverse structure with an uneven distribution of particle sizes. The maximum entrapment efficiency of 95.5% ± 1.25% was achieved. The obtained findings revealed that The minimum inhibitory concentration and minimum bactericidal concentration values were determined to be 5 and 10 ug/ml, respectively, indicating the potent bactericidal effect of the NPs. Also, S. aureus infected rats explored upregulation in the mRNA expression of TLR2 and TLR4 compared to healthy control groups. AV-CS-NP treatment reverses the case where there was repression in mRNA expression of TLR2 and TLR4 compared to S. aureus-treated rats. Conclusion: These NPs can serve as potential candidates for the development of alternative antimicrobial agents.


Assuntos
Lesão Pulmonar Aguda , Aloe , Quitosana , Nanopartículas , Doenças dos Roedores , Ratos , Animais , Quitosana/química , Quitosana/farmacologia , NF-kappa B/farmacologia , Staphylococcus aureus , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Nanopartículas/química , Transdução de Sinais , Antibacterianos/farmacologia , Lesão Pulmonar Aguda/veterinária , Inflamação/veterinária , RNA Mensageiro/farmacologia
2.
Cureus ; 15(10): e46873, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37954739

RESUMO

OBJECTIVES: Multiple sclerosis (MS) is a disease of the central nervous system (CNS). Several factors, including sex, body mass index (BMI), disease duration, and age of onset, have been identified as predictors of disease severity. This study investigated the association between the aforementioned factors and MS severity, measured by the number of hospital visits and admissions, length of stay, and frequency of methylprednisolone use. METHODS: This retrospective cross-sectional analysis used data obtained from BESTCare at the King Abdulaziz Medical City (KAMC). A total of 272 patients with MS and their demographic and clinical characteristics were included. RESULTS: The study population consisted of 68.75% (n = 187) females and 31.25% (n = 85) males. The regression analyses indicated that disease duration was a significant predictor of the number of hospital visits and admissions (p < 0.01). The study found a significant association between BMI (unstandardized beta (B) = -0.25, 95% confidence interval (CI) = -0.47, -0.02, p = 0.033), age at diagnosis (unstandardized beta (B) = 0.15, 95% CI = 0.001, 0.31, p = 0.048), and length of hospital stay. Additionally, there was a significant correlation between disease duration and the number of methylprednisolone doses (unstandardized beta (B) = 0.45, 95% CI = 0.01, 0.89, p = 0.045). CONCLUSION: Disease duration was found to be a significant predictor of hospital visits, admissions, and methylprednisolone use, while sex and BMI did not contribute to the variation in these outcomes. However, BMI and age of onset were significantly associated with length of hospital stay.

3.
Egypt J Immunol ; 30(4): 145-154, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37801033

RESUMO

Although many drugs are available for childhood systemic lupus erythematosus (SLE) treatment, the adverse effects and poor response in some cases make it crucial to find new drugs targeting various pathways in disease pathogenesis to improve overall outcomes. This study aimed to (i) investigate the effect of Panobinostat on cultured lymphocytes obtained from children with active SLE and (ii) to compare that effect with standard drugs used in SLE, such as Prednisone and hydroxychloroquine. The study included 24 SLE active patients, divided into four equal groups. Lymphocytes were isolated from blood samples of the study patients. According to the study group, cells were treated with either Panobinostat, Prednisolone, hydroxychloroquine, or not treated (control group). After cell culture, the response of lymphocytes upon drug treatment was analyzed in terms of the production of anti-dsDNA antibodies and levels of apoptosis as detected by flow cytometry using annexin V and propidium iodide (PI) staining. The Panobinostat group showed a significant decrease in the viable cell count (p < 0.001). Both Prednisone and hydroxychloroquine decreased anti-dsDNA expression more than the Panobinostat and control groups (p < 0.001 for both). PI was higher in the Prednisone group, and Annexin V was higher in the Panobinostat group compared to other groups; however, their increase did not reach statistically significant levels (p= 0.12 and 0.85, respectively). This is the first study of the Panobinostat effect on cultured lymphocytes of SLE. In conclusion, Panobinostat could be a prospective treatment for B-cell-driven autoimmune diseases such as SLE. However, its effect on autoantibodies levels and different clinical features of SLE still need a thorough evaluation.


Assuntos
Hidroxicloroquina , Lúpus Eritematoso Sistêmico , Humanos , Criança , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Panobinostat/farmacologia , Panobinostat/uso terapêutico , Prednisona/farmacologia , Prednisona/uso terapêutico , Anexina A5/farmacologia , Anexina A5/uso terapêutico , Linfócitos
4.
Biomed Chromatogr ; 37(12): e5747, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37728037

RESUMO

Fifty diabetic nephropathy (DN) children with type 1 diabetes mellitus (T1DM) and 50 healthy matched controls were included. Chromatographic assays of 14 amino acids, free carnitine and 27 carnitine esters using high-performance liquid chromatography/electrospray ionization-mass spectroscopy, and genetic testing for JAK2v617f mutation using real-time PCR were performed. Patients had significantly lower levels of tyrosine, branched-chain amino acids (BCAAs), and BCAA/AAA (aromatic chain amino acids) ratios, glycine, arginine, ornithine, free carnitine and some carnitine esters (C5, 6, 12 and 16) and higher phenylalanine, phenylalanine/tyrosine ratio and C18 compared with the controls and in the macro-albuminuria vs. the microalbuminuria group (p < 0.05 for all) except for free carnitine. Plasma carnitine was negatively correlated with eGFR (r = -0.488, p = 0.000). There were significant positive correlations between tyrosine with UACR ratio (r = 0.296, p = 0.037). The plasma BCAA/AAA ratio showed significant negative correlations with UACR (r = -0.484, p = 0.000). There was a significantly higher frequency of the JAK2V617F gene mutation in diabetic nephropathy patients compared with the control group and in macro-albuminuria than the microalbuminuria group (p = 0.000) for both. When monitoring children with T1DM, plasma free amino acids and acylcarnitine profiles should be considered, especially if they have tested positive for JAK2V617F for the early diagnosis of DN.


Assuntos
Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Humanos , Criança , Aminoácidos , Diabetes Mellitus Tipo 1/genética , Nefropatias Diabéticas/genética , Albuminúria , Carnitina , Tirosina , Fenilalanina , Mutação , Janus Quinase 2/genética
5.
Arch. endocrinol. metab. (Online) ; 67(3): 395-400, June 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1429746

RESUMO

ABSTRACT Objectives: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusions: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

6.
J Biochem Mol Toxicol ; 37(6): e23350, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36988379

RESUMO

Doxorubicin (DOX) is one of the basic anticancer drugs, nonetheless its use is restricted due to noxious side effects. Kidney failure is one of the main side effects that restrict its medical use. The current study assessed the nephroprotective effects of fenofibrate and pioglitazone against the renal injury induced by doxorubicin in rats and illustrated the probable mechanisms underlying these protective effects. For this purpose, Male Sprague-Dawley rats weighing (200-230 g) were allocated into seven groups treated for 15 days as following: control (50% corn oil + 50% DMSO p.o), fenofibrate (100 mg/kg p.o) and pioglitazone (10 mg/kg p.o) as well as four groups of DOX (15 mg/kg i.p on 11th day). DOX groups included DOX alone and DOX with protective drugs fenofibrate, pioglitazone or both of them. As a result of doxorubicin nephrotoxicity; serum creatinine and blood urea nitrogen were remarkably elevated. Moreover, renal glutathione was significantly reduced while tissue lipid peroxidation malondialdehyde, tumor necrosis factor-α, nuclear factor-kappa B p65 (NF-κB p65), interleukin-1ß, p38 mitogen activated protein kinase (p38-MAPK) and caspase-3 (Casp-3) were significantly augmented. Treatment with fenofibrate and pioglitazone either alone or in combination markedly attenuated DOX-induced injury by suppression of oxidative stress, inflammation and apoptosis. The above-mentioned biochemical markers were affirmed by histological assessment. In conclusion, fenofibrate, pioglitazone, and their combination possess potential prophylactic effects against doxorubicin-induced renal injury through modulation of p38-MAPK/NF-κB p65 pathway with superiority to the combination.


Assuntos
Fenofibrato , Insuficiência Renal , Ratos , Masculino , Animais , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Pioglitazona/farmacologia , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/farmacologia , Fenofibrato/farmacologia , Fenofibrato/metabolismo , Rim , Doxorrubicina/efeitos adversos , Estresse Oxidativo , Hipoglicemiantes/farmacologia , Apoptose
7.
Arch Endocrinol Metab ; 67(3): 395-400, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36748933

RESUMO

Objective: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusion: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.


Assuntos
Doença de Hashimoto , Hipotireoidismo , Reserva Ovariana , Tireoidite Autoimune , Feminino , Humanos , Adolescente , Hormônio Antimülleriano , Tireotropina
8.
AJPM Focus ; 1(2): 100031, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36457954

RESUMO

Introduction: This study aimed to explore the impact of the COVID-19 pandemic on routine immunization along 4 abbreviated time frames: before the pandemic in 2019, stay-at-home period (March-May) in 2020, reopening period (June-August) in 2020, and corresponding months in 2021. Methods: A secondary analysis of immunization data in Kuwait during the prepandemic period in 2019, stay-at-home period (March-May) in 2020, reopening period (June-August) in 2020, and corresponding months in 2021 was conducted. All vaccines given at 2, 3, 6, 12, 18, and 24 months of age were included in the study. Results: The mean of total visits from March 2020 to May 2020 dropped (-28.9%) compared with the visits in March 2019-May 2019 and then increased during the reopening period in June 2020-August 2020 (+31.8%). All vaccinations scheduled for children aged ≤24 months showed a reduction. The greatest reduction was detected at age 24 months (-44.2%), followed by age 18 months (-36.5%) and then age 1 year (-28.8%). There were greater declines among non-Kuwaiti children than among Kuwaiti children for all types of vaccines. The mean of total visits in March 2021-May 2021 increased (+15.4%) compared with the mean in the same period in 2020. However, a reduction of -16.0% still exists compared with the reduction at baseline in 2019. Conclusions: The COVID-19 pandemic had a large impact on childhood vaccinations, with recovery in subsequent months.

9.
Mol Divers ; 26(1): 171-181, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33389441

RESUMO

Coronavirus diseases 2019 (COVID-19) are seriously affecting human health all over the world. Nucleotide inhibitors have promising results in terms of its efficacy against different viral polymerases. In this study, detailed molecular docking and dynamics simulations are used to evaluate the binding affinity of a clinically approved drug, sofosbuvir, with the solved structure of the viral protein RNA-dependent RNA polymerase (RdRp) and compare it to the clinically approved drug, Remdesivir. These drugs are docked onto the three-dimensional structure of the nsp12 protein of SARS-CoV-2, which controls the polymerization process. Hence, it is considered one of the primary therapeutic targets for coronaviruses. Sofosbuvir is a drug that is currently used for HCV treatment; therefore, HCV RdRp is used as a positive control protein target. The protein dynamics are simulated for 100 ns, while the binding is tested during different dynamics states of the SARS-CoV-2 RdRp. Additionally, the drug-protein complexes are further simulated for 20 ns to explore the binding mechanism. The interaction of SARS-CoV-2 RdRp as a target with the active form of sofosbuvir as a ligand demonstrates binding effectiveness. One of the FDA-approved antiviral drugs, such as sofosbuvir, can help us in this mission, aiming to limit the danger of COVID-19. Sofosbuvir was found to bind nsp12 with comparable binding energies to that of Remdesivir, which has been reported for its potential against COVID-19 RdRp and is currently approved by the FDA.


Assuntos
Tratamento Farmacológico da COVID-19 , Sofosbuvir , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/química , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , RNA Viral , RNA Polimerase Dependente de RNA , SARS-CoV-2 , Sofosbuvir/farmacologia , Sofosbuvir/uso terapêutico
10.
J Pediatr Endocrinol Metab ; 35(1): 79-87, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-34787382

RESUMO

OBJECTIVES: This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). METHODS: Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes' frequencies were compared between cases and controls and between patients with BMD z-scores above and below -2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). RESULTS: The patients aged 14.01 ± 2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below -2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below -2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below -2 (p=0.01, 0.01, <0.001, respectively). Regression analysis showed T allele of rs2073617, duration of illness (above 36 months), and cumulative SLEDAI (above 10) as independent predictors of decreased BMD (p 0.02, 0.003, and 0.002, respectively). CONCLUSIONS: This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617 T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.


Assuntos
Densidade Óssea , Lúpus Eritematoso Sistêmico/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Alelos , Criança , Feminino , Genótipo , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Osteoporose/etiologia
11.
Molecules ; 26(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34770863

RESUMO

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.


Assuntos
Coronavirus/metabolismo , Interações entre Hospedeiro e Microrganismos/fisiologia , Receptores de Coronavírus/metabolismo , Anticorpos Neutralizantes , Antivirais/farmacologia , COVID-19 , Coronavirus/patogenicidade , Humanos , Receptores de Coronavírus/fisiologia , Receptores Virais/metabolismo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos
12.
Lupus ; 30(9): 1449-1458, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34080911

RESUMO

BACKGROUND: Many genes have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF) is a potent cytokine stimulator acting through 2 cell surface receptors (TNFR I and II). TNFRII gene which controls expression of these receptors has been linked to SLE susceptibility through promoting apoptosis. Also; Protein tyrosine phosphatase non receptor 22 (PTPN22) gene enhances intrinsic phosphatase activity of T lymphocytes leading to their dysregulation and stimulates autoimmune process of lupus and its rs2476601 has been linked to susceptibility to thyroiditis in SLE patients in few studies. OBJECTIVES: (i) to investigate the correlation between 2 SNPs of TNFR II and PTPN22 genes and SLE susceptibility in a cohort of Egyptian children compared to controls (ii) and to investigate their possible association with different clinical presentations of the disease in children. SUBJECTS AND METHODS: Typing of TNFR II rs1061622 and PTPN22 rs2476601 SNPs were done using polymerase chain reaction-restriction fragment length polymorphism for 74 children with SLE and 100 matched healthy controls. RESULTS: Children with SLE had more frequent G allele and GG genotype of TNFR II rs1061622 (p < 0.001) and more T allele and TT genotype of PTPN22 rs2476601 (p = 0.012 and <0.001, respectively) compared to controls. Only 6 patients (8%) had thyroiditis (hypothyroidism) with T allele and TT genotype of PTPN22 1858 T more prevalent in those patients versus those without thyroiditis (p ≤ 0.001). Apart from, thyroiditis, no significant association was found between genotypes and alleles frequencies of the 2 studied SNPs and other clinical manifestations of the disease. CONCLUSION: The G allele and GG genotype of TNFR II rs1061622 and T allele and TT genotype of PTPN22 rs2476601 genes polymorphism can be considered as risk factors for the development of SLE. The presence of the T allele of PTPN22 rs2476601 may increase the risk of concomitant thyroiditis in Egyptian children with SLE but further studies are required to confirm this finding as thyroiditis was reported only in few cases in this study.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Adolescente , Estudos de Casos e Controles , Criança , Egito/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/imunologia , Receptores Tipo II do Fator de Necrose Tumoral/imunologia , Risco , Linfócitos T/imunologia
13.
J Biomol Struct Dyn ; 39(8): 2923-2931, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32306854

RESUMO

The Middle East Respiratory Syndrome Coronavirus (MERS CoV), also termed camel flu, is a new viral infection that first reported in the year 2012 in the Middle East region and further spread during the last seven years. MERS CoV is characterized by its high mortality rate among different human coronaviruses. MERS CoV polymerase shares more than 20% sequence identity with the Hepatitis C Virus (HCV) Non-structural 5b (NS5b) RNA dependent RNA polymerase (RdRp). Despite the low sequence identity, the active site is conserved between the two proteins, with two consecutive aspartates that are crucial in the nucleotide transfer reaction. In this study, seven nucleotide inhibitors have been tested against MERS CoV RdRp using molecular modeling and docking simulations, from which four are novel compounds. Molecular Dynamics Simulation for 260 nanoseconds is performed on the MERS CoV RdRp model to test the effect of protein dynamics on the binding affinities to the tested nucleotide inhibitors. Results support the hypothesis of using the anti-polymerases (Anti-HCV drugs) against MERS CoV RdRp as a potent candidates. Besides four novel compounds are suggested as a seed for high performance inhibitors against MERS CoV RdRp.Communicated by Ramaswamy H. Sarma.


Assuntos
Coronavírus da Síndrome Respiratória do Oriente Médio , Antivirais/farmacologia , Simulação por Computador , Guanosina , SARS-CoV-2
14.
Int J Dermatol ; 59(1): e14-e15, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31646615
15.
J Infect Public Health ; 10(5): 667-673, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28642140

RESUMO

Carbapenemase-producing Enterobacteriaceae have been steadily spreading worldwide during the last decade. Nine patients were identified prospectively and were followed during their hospitalization course to identify the epidemiology, clinical profiles and outcomes. These patients had one or more cultures positive for a CRE isolate, contributing to a total of eleven positive cultures from various sites without including duplicates of isolates obtained from the same site. Isolates from these patients included five Klebseilla pneumoniae, three Escherichia coli, and one Enterobacter aerogenes. Five isolates were grown from blood cultures, three from wound cultures, one from urine cultures, one from respiratory cultures and one from an abscess collection. Five survived the hospital course. The other five patients died due to severe sepsis, septic shock or multi-organ failure. Of the nine isolates of CRE identified for which molecular analysis were available, four K. pneumonia were confirmed as blaNDM and one as OXA-48. For the purpose of controlling the spread of CRE in our institution, we recommend considering active surveillance cultures and screening patients transferred from other hospitals or coming from highly endemic settings at admission for these organisms.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Doenças Transmissíveis Emergentes/microbiologia , Infecções por Enterobacteriaceae/microbiologia , Hospitais Universitários , Adulto , Idoso , Carbapenêmicos , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/fisiopatologia , Enterobacter aerogenes/efeitos dos fármacos , Enterobacter aerogenes/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/fisiopatologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Arábia Saudita/epidemiologia
16.
Medicine (Baltimore) ; 96(51): e9336, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29390512

RESUMO

RATIONALE: Herein, we present a case of seemingly unprovoked portal vein thrombosis (PVT) occurring in the context of an acute cytomegalovirus (CMV) infection and prolonged debilitating fatigue. PATIENT CONCERNS: A 46-year-old male airline pilot presented with a 2 week history of abdominal pain, nausea, vomiting, watery diarrhea, and daily recurrent fevers. This was in the context of progressive, debilitating fatigue for 3 months forcing the patient to leave his job. DIAGNOSES: Computed tomography of the abdomen revealed PVT, which was managed initially by heparin infusion. Cefepime was ordered for broad-spectrum antibiotic management of sepsis and possible septic thrombosis. Further workup exposed elevated transaminases consistent with mild hepatitis without synthetic dysfunction and colonoscopy revealed colitis. A comprehensive evaluation for liver disease was notable for a markedly elevated ferritin level. Spiking fevers and neutrophilia persisted for several days despite empiric antimicrobial treatment, but eventually resolved. The remainder of the workup was negative except for positive CMV IgM titer and viral load. This raised suspicion for a hypercoagulable state caused by CMV hepatitis with CMV-induced PVT. Heparin was transitioned to warfarin at the time of discharge. INTERVENTIONS: Given the patient's immunocompetent state and resolution of fevers, antiviral therapy for CMV infection was not initiated. OUTCOMES: The patient continued to improve with a normalization of the serum ferritin level and anticoagulation therapy was stopped after 6 months. LESSONS: There is mounting support for infectious causes of venous thromboembolism (VTE) based on existing molecular biology and clinical research. Meta-analysis of existing data showed that between 1.9% and 9.1% of patients hospitalized with VTE had concurrent acute CMV infection. Theoretical mechanisms for this association include transient formation of antiphospholipid antibodies, transient formation of antibodies targeting CMV capsule phospholipids with procoagulant properties, and direct infection of the endothelial cells. We hope this case will serve as a reminder to consider CMV as a transient cause of PVT and VTE, particularly in light of 2016 guidelines for unprovoked VTE recommending lifelong anticoagulation. We also plan to prospectively study the association of unprovoked VTE and acute CMV infection in our own hospital system.


Assuntos
Infecções por Citomegalovirus/complicações , Veia Porta , Tromboembolia Venosa/virologia , Anticoagulantes/uso terapêutico , Fadiga/etiologia , Hepatite Viral Humana/complicações , Hepatite Viral Humana/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pilotos , Tromboembolia Venosa/tratamento farmacológico
17.
J Cardiothorac Surg ; 11(1): 128, 2016 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-27495807

RESUMO

BACKGROUND: Primary malignant tracheal tumors are rare, accounting for approximately 0.2 % of respiratory tract tumors yearly, with squamous cell carcinomas and adenoid cystic carcinomas accounting for two-thirds of these cases. Sarcomatoid carcinomas are a group of poorly differentiated non-small cell lung carcinomas containing a component of sarcoma or sarcoma-like (spindle and/or giant cell) differentiation, categorized into five morphologic subgroups. Spindle cell sarcomatoid carcinoma is a rare variant of sarcomatoid carcinomas, consisting of only spindle-shaped tumor cells. Only one other case has been reported as a primary tracheal tumor. CASE PRESENTATION: We present a 75-year-old male, having progressive dyspnea and cough, with a spindle cell sarcomatoid carcinoma tumor visualized on chest computed tomography scan and confirmed with biopsy. CONCLUSIONS: Due to its low incidence, knowledge of treatment methods, prognostic factors, and etiology is limited thus approaches to eradication have widely varied. We are reporting the second published case of spindle cell sarcomatoid carcinoma of the trachea and the first reported successful outcome of definitive treatment with tracheal resection.


Assuntos
Carcinoma/patologia , Carcinoma/cirurgia , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias da Traqueia/patologia , Neoplasias da Traqueia/cirurgia , Idoso , Carcinoma/diagnóstico por imagem , Humanos , Masculino , Sarcoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/diagnóstico por imagem
18.
Saudi J Biol Sci ; 17(2): 177-83, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23961075

RESUMO

The harvested eggs of Rhynchophorus ferrugineus are ovo-cylindrical shaped, averaged 1.09 mm in length and 0.43 mm in width, with ratio of [Formula: see text] 4.42. The chorionic layer of electron dense material is seen covering the exochorion structure of the eggs. The egg main body chorion exhibits a polygonal pattern and architecture surface of the egg is supported by a system of irregular interconnecting grooves. The micropylar apparatus of the eggs of the Red Palm Weevil, R. ferrugineus is described in the present study for the first time. Two micropylar openings are found closed to the center of the posterior wide pole of the egg. Each micropylar opening presents a single small orifice and its surrounding chorion is porous and densely set with tiny projections allowing the spermatozoa to penetrate the egg. Respiratory aeropyles are distributed on the borders of reticulations in the area chorionic surface of egg capsule. The hatching region is detected on the anterior part at the opposite side of the egg. Changes in the appearance and shape of R. ferrugineus eggs as well as the incidence of embryonic development are observed.

19.
Phys Rev C Nucl Phys ; 33(6): 2128-2131, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9953396
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