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1.
Environ Res ; 237(Pt 1): 116691, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37574097

RESUMO

Conductive agro-industrial wastes as accelerants in the anaerobic digestion (AD) of organic waste is a good technique for developing a rural circular economy, such as producing bioenergy and biofertilizer. This study disclosed the a role of sugar cane bagasse ash (SCBA) in enhancing the bioenergy (biogas) yield and digestate fertility via anaerobic co-digestion (AcoD) of buffalo dung (BD) and vegetable residue (VR) under mesophilic conditions (37 á´¼C). Firstly, an optimal BD/VR ratio (1:3) was determined based on biogas yield by introducing five different BD/VR ratios (1:0, 3:1, 1:1, 1:3, and 0:1) into AcoD systems. Secondly, the biogas yield was increased further by adding SCBA at five different concentrations (0, 0.5, 1, 1.5, and 2 wt%). Experimental results disclosed that the 1.5 wt% of SCBA gave the highest cumulative biogas yield (153.67 mL/g VS), COD removal rate (31.18%), and fertility (5.08%). Moreover, a framework is suggested to understand the role of SCBA in the enhanced DIET mechanism. This work documents an environmentally friendly and economical technique for developing a rural circular bioeconomy via the AD of organic agro-waste.

2.
J Infect Public Health ; 16(5): 680-688, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36934642

RESUMO

BACKGROUND: Infection with SARS-CoV-2 may perturb normal microbiota, leading to secondary infections that can complicate the viral disease. The aim of this study was to probe the alteration of nasopharyngeal (NP) microbiota in the context of SARS-CoV-2 infection and obesity and to identify other respiratory pathogens among COVID-19 cases that may affect patients' health. METHODS: A total of 107 NP swabs, including 22 from control subjects and 85 from COVID-19 patients, were processed for 6S amplicon sequencing. The respiratory pathogens causing secondary infections were identified by RT-PCR assay, using a kit that contained specific primers and probes combinations to amplify 33 known respiratory pathogens. RESULTS: No significant (p > 0.05) difference was observed in the alpha and beta diversity analysis, but specific taxa differed significantly between the control and COVID-19 patient groups. Genera of Sphingomonas, Kurthia, Microbacterium, Methylobacterium, Brevibacillus, Bacillus, Acinetobacter, Lactococcus, and Haemophilus was significantly abundant (p < 0.05) in COVID-19 patients compared with a healthy control group. Staphylococcus was found in relatively high abundance (35.7 %) in the COVID-19 patient groups, mainly those treated with antibiotics. A relatively high percentage of Streptococcus was detected in COVID-19 patient groups with obesity or other comorbidities. Respiratory pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Salmonella species, along with Pneumocystis jirovecii fungal species were detected by RT-PCR mainly in the COVID-19 patients. Klebsiella pneumoniae was commonly found in most of the samples from the control and COVID-19 patients. Four COVID-19 patients had viral coinfections with human adenovirus, human rhinovirus, enterovirus, and human parainfluenza virus 1. CONCLUSIONS: Overall, no substantial difference was observed in the predominant NP bacterial community, but specific taxa were significantly changed between the healthy control and COVID-19 patients. Comparatively, an increased number of respiratory pathogens were identified in COVID-19 patients, and NP colonization by K. pneumoniae was probably occurring in the local population.


Assuntos
COVID-19 , Coinfecção , Microbiota , Infecções Respiratórias , Humanos , Arábia Saudita/epidemiologia , SARS-CoV-2 , Nasofaringe , Klebsiella pneumoniae , Obesidade , Infecções Respiratórias/epidemiologia
3.
Vaccines (Basel) ; 11(2)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36851205

RESUMO

Iron is a crucial micronutrient for immunity induction in response to infections and vaccinations. This study aimed to investigate the effect of iron deficiency on COVID-19-vaccine-induced humoral immunity. We investigated the effectiveness of COVID-19 vaccines (BNT162b2, mRNA-1273, and ChAdOx nCov-2019) in iron-deficient individuals (n = 63) and provide a side-by-side comparison to healthy controls (n = 67). The presence of anti-SARS-CoV-2 spike (S) and anti-nucleocapsid (NP) IgG were assessed using in-house S- and NP-based ELISA followed by serum neutralization test (SNT). High concordance between S-based ELISA and SNT results was observed. The prevalence of neutralizing antibodies was 95.24% (60/63) in the study group and 95.52% (64/67) in the controls with no significant difference. The presence/absence of past infection, period since vaccination, vaccine type, and being iron-deficient or having iron-deficiency anemia did not exert any significant effect on the prevalence or titer of anti-SARS-CoV-2 neutralizing antibodies. NP-based ELISA identified individuals unaware of exposure to SARS-CoV-2. Moreover, absence of anti-NP IgG was noted in participants who were previously diagnosed with COVID-19 suggesting the unpredictability of after-infection immunity. To sum up, this study demonstrated an initial lack of evidence on the association between iron deficiency and the effectiveness of COVID-19-vaccine-induced neutralizing humoral immunity. Similar studies with larger sample size remain necessary to obtain comprehensive conclusions about the effect or lack of effect of iron on COVID-19-vaccine effectiveness.

4.
Int J Gen Med ; 15: 6405-6413, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957758

RESUMO

Aim: To examine the effect of weight-loss induced bariatric procedures on albuminuria levels among diabetic patients suffering from obesity. Methods: Adults patients who suffer from morbid obesity and type 2 diabetes mellitus (T2DM) were included in a prospective cohort study. Subjects were scheduled to undergo laparoscopic sleeve gastrectomy (LSG) or one-anastomosis gastric bypass (OAGB). The albumin-to-creatinine ratio (ACR) was adopted to assess the degree of albuminuria. Microalbuminuria was determined as a ratio of >2.5-30 mg/mmol and >3.5-30 mg/mmol for males and females, respectively, while macroalbuminuria was diagnosed when the ACR exceeded >30 mg/mmol. Results: The mean uACR decreased significantly from 20.95±16.89 to 9.92±12.69mg/mmol in LSG cohort (p <0.001), and from 19.52±16.65 to 9.34±11.77mg/mmol in the OAGB cohort, with no statistically considerable differences between both cohorts at the end of follow-up (p = 0.78). Twelve months after the procedures, the percentages of cases with microalbuminuria decreased significantly to 23.8% and 23.9%, respectively (p < 0.001); likewise, the percentages of cases with macroalbuminuria significantly decreased to 7.9% and 7.5% in the LSG and OAGB groups, respectively (p < 0.001). There were no statistically considerable differences between LSG and OAGB regarding the percentages of patients with micro or macroalbuminuria at the end of follow-up. Besides, there were no significant associations between the degree of weight loss and improvement (p = 0.959) or remission (p = 0.73) of microalbuminuria. Conclusion: Bariatric surgery significantly reduced the severity of albuminuria 1-year after the procedure, with no preference for one procedure over the other.

5.
Heliyon ; 8(8): e10084, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36039128

RESUMO

Background: Novel psychoactive substances (NPSs) are relatively new substances in the illicit drug market, not previously listed in the United Nations Office on Drugs and Crime (UNDOC). Strox and Voodoo are considered some of the most popular blends of NPS in the Egyptian drug market. Objectives: The current study was conducted to assess NPS's use pattern: Voodoo and Strox among acutely intoxicated patients presented to the poison control center of Ain Shams University Hospitals (PCC- ASUH). Methods: A single center based cross-sectional study was carried out in the PCC-ASUH among acutely intoxicated patients presenting to the emergency department (ED) over four months (from January-April 2019. using a previously adopted and validated Fahmy and El-Sherbini socioeconomic scale (SES). Data were presented as mean, median and range as appropriate. Both smoking and crowding indexes were calculated and presented as previously reported. Results: Fifty-one patients were presented to the ED of PCC-ASUH during the study period. A total of 96.1% (n = 49) were males. The mean age was 25 ± 7.5 years. The most common NPS used was Strox: 54.9% (n = 28), followed by Voodoo: 27.4% (n = 14). Neurological and gastrointestinal (GI) symptoms were the most frequent presentations. The most common motive behind NPS use was the desire to give a trial of new psychoactive substances. The mean SES score was 35.1 ± 13.17. Most patients have the preparatory as the highest education 36.0% (n = 18). Conclusions: NPS use is common among young males in preparatory education from different social classes, starting it most commonly as a means to experiencing a new high. Neurological and GI manifestations are the most common presenting symptoms of NPS intoxication.

6.
Materials (Basel) ; 15(8)2022 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35454620

RESUMO

The current work investigates the viability of utilizing a friction stir deposition (FSD) technique to fabricate continuous multilayer high-performance, metal-based nanoceramic composites. For this purpose, AA2011/nano Al2O3 composites were successfully produced using AA2011 as a matrix in two temper conditions (i.e., AA2011-T6 and AA2011-O). The deposition of matrices without nano Al2O3 addition was also friction stir deposited for comparison purposes. The deposition process parameters were an 800 rpm rod rotation speed and a 5 mm/min feed rate. Relative density and mechanical properties (i.e., hardness, compressive strength, and wear resistance) were evaluated on the base materials, deposited matrices, and produced composites. The microstructural features of the base materials and the friction stir deposited materials were investigated using an optical microscope (OM) and a scanning electron microscope (SEM) equipped with an EDS analysis system. The worn surface was also examined using SEM. The suggested technique with the applied parameters succeeded in producing defect-free deposited continuous multilayer AA2011-T6/nano Al2O3 and AA2011-O/nano Al2O3 composites, revealing well-bonded layers, grain refined microstructures, and homogeneously distributed Al2O3 particles. The deposited composites showed higher hardness, compressive strengths, and wear resistance than the deposited AA2011 matrices at the two temper conditions. Using the AA2011-T6 temper condition as a matrix, the produced composite showed the highest wear resistance among all the deposited and base materials.

7.
Obes Surg ; 32(3): 779-785, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35013896

RESUMO

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is one of the most effective bariatric procedures. The study aimed to explore the value of lengthening the biliopancreatic limb (BPL) in RYGB compared to the outcome of one-anastomosis gastric bypass (OAGB). METHODS: This prospective study included morbidly obese patients divided into two groups. The RYGB group (n = 36) was subjected to long biliary limb Roux-en-Y gastric bypass (LPRYGB), and the OAGB Group (n = 36) had one anastomosis gastric bypass. During follow-up, weight, BMI, percentage of excess body weight loss (%EBWL), resolution of obesity-related comorbidities, and quality of life (QoL) were evaluated. RESULTS: There was no significant difference in weight and BMI after 3 and 6 months. At 12-month follow-up, weight loss was significantly higher in the OAGB group. After 12 months, the two groups showed significant improvement of comorbid conditions without significant difference between the two groups. The Qol was significantly higher in the LPRYGB group 3, 6, and 12 months after surgery compared to the OAGB group. CONCLUSIONS: Extending the BPL length in RYGB to 150 cm is as effective as OAGB in remission of comorbidities, including diabetes. It was also equally effective in weight reduction in the short term. OAGB was more efficient in weight reduction and a significantly faster operation. LPRYGB showed a better QoL of life 1 year after surgery.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Anastomose em-Y de Roux , Derivação Gástrica/métodos , Humanos , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Redução de Peso
8.
Int J Infect Dis ; 110: 267-271, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34289407

RESUMO

Immunocompromised patients who have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection pose many clinical and public health challenges. We describe the case of a hematopoietic stem cell transplantation patient with lymphoma who had a protracted illness requiring three consecutive hospital admissions. Whole genome sequencing confirmed two different SARS-CoV-2 clades. Clinical management issues and the unanswered questions arising from this case are discussed.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , Reinfecção , SARS-CoV-2 , Eliminação de Partículas Virais
9.
World J Surg ; 45(10): 3130-3137, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34175966

RESUMO

BACKGROUND: The effect of bariatric surgery on postoperative thyroid function remains incompletely understood. In this study, we aimed to evaluate the changes in thyroid functions after gastric sleeve operation for morbidly obese Egyptian patients. METHODS: This was a prospective study that recruited 128 patients who underwent sleeve gastrectomy through the period from December 2016 to April 2020. We measured thyroid-stimulating hormone (TSH), free thyroxin (FT4), and free triiodothyronine. Subclinical hypothyroidism was defined by a TSH level > 4.5 mIU/L but a normal FT4 level. All patients were followed for 12 months after the procedure. RESULTS: Preoperatively, 30 (23.4%) patients had subclinical hypothyroidism. The prevalence of subclinical hypothyroidism decreased significantly to reach 7.8% at the end of follow-up (p < 0.001). None of the patients developed de novo hypothyroidism at the end of follow-up. Patients with subclinical hypothyroidism were more likely to be females (p = 0.037) and had significantly higher waist circumference (p < 0.001), DBP (p = 0.02), serum cholesterol (p < 0.001), and serum triglyceride (p < 0.001). However, patients with subclinical hypothyroidism at the end of follow-up had significantly higher BMI at the end of the sixth month (p = 0.048). Similarly, patients with subclinical hypothyroidism at the end of follow-up had significantly higher serum cholesterol (p = 0.002), LDL, (p = 0.038), and serum triglyceride (p < 0.001) at the end of the sixth months of follow-up. A similar trend was noted at the end of the 12th month. The preoperative value of serum TSH correlated significantly with serum cholesterol and triglyceride levels. CONCLUSION: The positive effect of the LSG procedure on the hypothyroid bariatric population, including enhanced thyroid function, was demonstrated.


Assuntos
Hipotireoidismo , Laparoscopia , Obesidade Mórbida , Feminino , Gastrectomia , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Masculino , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
10.
World J Urol ; 39(12): 4477-4482, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34076752

RESUMO

OBJECTIVE: To assess the effect and outcome of percutaneous nephrolithotomy (PNL) versus extracorporeal shock wave lithotripsy (SWL) in patients with renal insufficiency. PATIENTS AND METHODS: A prospective randomized clinical study of 104 renal insufficiency patients with renal stones (serum creatinine 2-4 mg/dl and eGFR < 60 ml/min/1.73 m2 more than 3 months) randomized into two groups: Group A underwent PNL; Group B underwent shock wave lithotripsy (SWL). Treatment effects and outcomes compared between the two groups. RESULTS: Between Group A of 50 patients and Group B of 54 cases, demographic data showed no statistically significant differences. The stone-free rate was 84% in Group A versus 26.6% in Group B after the first SWL session. After completion of all SWL sessions, the rate was 88.9% for Group B. Comparing pre and postoperative results of Group A, there is significant improvement of serum creatinine concentrations by 9.1% (p = 0.001), significant improvement of creatinine clearance (p = 0.000) and eGFR (p = 0.003). Although regarding Group B preoperatively and 3 months after SWL there is significant improvement by 8.7% (p = 0.0001), which is less than that of Group A, there is also, improvement of eGFR by 6.7% (p = 0.001), which is less than the eGFR improvement in Group A (12.3%). But there is no statistically significant difference is noted for creatinine clearance in Group B (p = 0.09). CONCLUSION: The outcomes for PNL and SWL in patients with renal insufficiency and renal stones are encouraging as minimally invasive procedures with no negative effects on kidney function.


Assuntos
Cálculos Renais/complicações , Cálculos Renais/terapia , Litotripsia , Nefrolitotomia Percutânea , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
11.
Int J Infect Dis ; 108: 112-115, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34004329

RESUMO

BACKGROUND: Immunocompromised patients with coronavirus disease 2019 (COVID-19) have prolonged infectious viral shedding for more than 20 days. A test-based approach is suggested for de-isolation of these patients. METHODS: The strategy was evaluated by comparing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (cycle threshold (Ct) values) and viral culture at the time of hospital discharge in a series of 13 COVID-19 patients: six immunocompetent and seven immunocompromised (five solid organ transplant patients, one lymphoma patient, and one hepatocellular carcinoma patient). RESULTS: Three of the 13 (23%) patients had positive viral cultures: one patient with lymphoma (on day 16) and two immunocompetent patients (on day 7 and day 11). Eighty percent of the patients had negative viral cultures and had a mean Ct value of 20.5. None of the solid organ transplant recipients had positive viral cultures. CONCLUSIONS: The mean Ct value for negative viral cultures was 20.5 in this case series of immunocompromised patients. Unlike those with hematological malignancies, none of the solid organ transplant patients had positive viral cultures. Adopting the test-based approach for all immunocompromised patients may lead to prolonged quarantine. Large-scale studies in disease-specific populations are needed to determine whether a test-based approach versus a symptom-based approach or a combination is applicable for the de-isolation of various immunocompromised patients.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Hospedeiro Imunocomprometido , Quarentena , Eliminação de Partículas Virais
12.
Mikrochim Acta ; 188(4): 137, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33763734

RESUMO

The novel corona (SARS-CoV-2) virus causes a global pandemic, which motivates researchers to develop reliable and effective methods for screening and detection of SARS-CoV-2. Though there are several methods available for the diagnosis of SARS-CoV-2 such as RT-PCR and ELSIA, nevertheless, these methods are time-consuming and may not apply at the point of care. In this study, we have developed a specific, sensitive, quantitative and fast detection method for SARS-CoV-2 by fluorescence resonance energy transfer (FRET) assay. The total extracellular protease proteolytic activity from the virus has been used as the biomarker. The specific peptide sequences from the library of 115 dipeptides were identified via changes in the fluorescence signal. The fluorogenic dipeptide substrates have the fluorophore and a quencher at the N- and the C- terminals, respectively. When the protease hydrolyzes the peptide bond between the two specific amino acids, it leads to a significant increase in the fluorescence signals. The specific fluorogenic peptide (H-d) produces a high fluorescence signal. A calibration plot was obtained from the changes in the fluorescence intensity against the different concentrations of the viral protease. The lowest limit of detection of this method was 9.7 ± 3 pfu/mL. The cross-reactivity of the SARS-CoV-2-specific peptide was tested against the MERS-CoV which does not affect the fluorescence signal. A significant change in the fluorescence signal with patient samples indicates that this FRET-based assay might be applied for the diagnosis of SARS-CoV-2 patients. Graphical abstract.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Proteases 3C de Coronavírus/metabolismo , Corantes Fluorescentes/metabolismo , Peptídeos/metabolismo , SARS-CoV-2 , Proteínas Virais/metabolismo , Animais , Bioensaio , COVID-19/microbiologia , Chlorocebus aethiops , Transferência Ressonante de Energia de Fluorescência , Humanos , Biblioteca de Peptídeos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Células Vero , Ensaio de Placa Viral
13.
Vox Sang ; 116(6): 673-681, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33277935

RESUMO

BACKGROUND AND OBJECTIVES: During the ongoing pandemic of COVID-19, SARS-CoV-2 RNA was detected in plasma and platelet products from asymptomatic blood donors, raising concerns about potential risk of transfusion transmission, also in the context of the current therapeutic approach utilizing plasma from convalescent donors. The objective of this study was to assess the efficacy of amotosalen/UVA light treatment to inactivate SARS-CoV-2 in human plasma to reduce the risk of potential transmission through blood transfusion. METHODS: Pools of three whole-blood-derived human plasma units (630-650 ml) were inoculated with a clinical SARS-CoV-2 isolate. Spiked units were treated with amotosalen/UVA light (INTERCEPT Blood System™) to inactivate SARS-CoV-2. Infectious titres and genomic viral load were assessed by plaque assay and real-time quantitative PCR. Inactivated samples were subject to three successive passages on permissive tissue culture to exclude the presence of replication-competent viral particles. RESULTS: Inactivation of infectious viral particles in spiked plasma units below the limit of detection was achieved by amotosalen/UVA light treatment with a mean log reduction of >3·32 ± 0·2. Passaging of inactivated samples on permissive tissue showed no viral replication even after 9 days of incubation and three passages, confirming complete inactivation. The treatment also inhibited NAT detection by nucleic acid modification with a mean log reduction of 2·92 ± 0·87 PFU genomic equivalents. CONCLUSION: Amotosalen/UVA light treatment of SARS-CoV-2 spiked human plasma units efficiently and completely inactivated >3·32 ± 0·2 log of SARS-CoV-2 infectivity, showing that such treatment could minimize the risk of transfusion-related SARS-CoV-2 transmission.


Assuntos
Furocumarinas/farmacologia , Plasma/virologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/efeitos da radiação , Terapia Ultravioleta , Inativação de Vírus , COVID-19/prevenção & controle , COVID-19/transmissão , Humanos , Reação Transfusional/prevenção & controle , Resultado do Tratamento
14.
Sci Rep ; 9(1): 20217, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882991

RESUMO

Inflammatory bowel disease (IBD) patients frequently suffer from anxiety disorders and depression, indicating that altered gut-brain axis signalling during gastrointestinal inflammation is a risk factor for psychiatric disease. Microglia, immune cells of the brain, is thought to be involved in a number of mental disorders, but their role in IBD is largely unknown. In the current work, we investigated whether colitis induced by dextran sulphate sodium (DSS), a murine model of IBD, alters microglial phenotypes in the brain. We found that colitis caused a reduction of Iba-1 and CD68 immunoreactivity, microglial activation markers, in specific brain regions of the limbic system such as the medial prefrontal cortex (mPFC), while other areas remained unaffected. Flow cytometry showed an increase of monocyte-derived macrophages during colitis and gene expression analysis in the mPFC showed pronounced changes of microglial markers including cluster of differentiation 86 (CD86), tumour necrosis factor-α, nitric oxide synthase 2, CD206 and chitinase-like protein 3 consistent with both M1 and M2 activation. Taken together, these findings suggest that experimental colitis-induced inflammation is propagated to the brain altering microglial function.


Assuntos
Encéfalo/metabolismo , Colite/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Microglia/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Colite/induzido quimicamente , Colite/genética , Sulfato de Dextrana , Expressão Gênica , Humanos , Doenças Inflamatórias Intestinais/genética , Ativação de Macrófagos , Macrófagos/classificação , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Microglia/citologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Córtex Pré-Frontal/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
Bioorg Chem ; 76: 154-165, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29175587

RESUMO

The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives based on our lead NCI 748494/1, possessing different N-linkers to aromatic and heterocyclic rings. In addition, a molecular hybrid series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-mercaptopurine (6-MP) was synthesized in order to explore its "double-drug" antitumor effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antitumor activity. Compound 3d showed potent inhibitory activity more than reference Foretinib, BMS-777607 and NCI 748494/1 with IC50 values in the range 0.01-0.31 µM against the cancer cell lines. The calculated IC50 of 3d against c-Met kinase was found to be 2.71 µM, which is more potent than NCI 748494/1 (IC50 = 31.70 µM). Docking studies were performed to identify the binding mode of 3d with c-Met kinase domain in comparison to moderate and weak derivatives. The present study clearly demonstrates that 1,2,4-triazine ring exhibits promising antitumor activity and the double-drug optimization strategy led to identifying 3d as a potent c-Met kinase inhibitor suitable for further development.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Triazinas/farmacologia , Aminopiridinas/farmacologia , Anilidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Domínio Catalítico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-met/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Piridonas/farmacologia , Quinolinas/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Triazinas/síntese química , Triazinas/química , Triazinas/metabolismo
16.
Bioorg Chem ; 73: 154-169, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28715754

RESUMO

In silico target fishing approach using PharmMapper server identified c-Met kinase as the selective target for our previously synthesized compound NCI 748494/1. This approach was validated by in vitro kinase assay which showed that NCI 748494/1 possessed promising inhibitory activity against c-Met kinase (IC50=31.70µM). Assessment of ADMET profiling, drug-likeness, drug score as well as docking simulation for the binding pose of that compound in the active site of c-Met kinase domain revealed that NCI 748494/1 could be considered as a promising drug lead. Based on target identification and validation, it was observed that there is structure similarity between NCI 748494/1 and the reported type II c-Met kinase inhibitor BMS-777607. Optimization of our lead NCI 748494/1 furnished newly synthesized 1,2,4-triazine derivatives based on well-established structure-activity relationships, whereas three compounds namely; 4d, 7a and 8c displayed excellent in vitro cytotoxicity against three c-Met addicted cancer cell lines; A549 (lung adenocarcinoma), HT-29 (colon cancer) and MKN-45 (gastric carcinoma); with IC50 values in the range 0.01-1.86µM. In vitro c-Met kinase assay showed 8c to possess the highest c-Met kinase inhibition profile (IC50=4.31µM). Docking of the active compounds in c-Met kinase active site revealed strong binding interactions comparable to the lead NCI 748494/1 and BMS-777607, suggesting that c-Met inhibition is very likely to be the mechanism of the antitumor effect of these derivatives.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Triazinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Relação Estrutura-Atividade , Triazinas/síntese química , Triazinas/química , Células Tumorais Cultivadas
17.
Environ Toxicol Pharmacol ; 54: 99-104, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28704756

RESUMO

The current study was performed to investigate the ameliorating effect of dietary supplementation of 0.5 and 1% Spiurolina platensis (SP) diet against the sub-acute toxicity of diazinon (DZN) 0.28mg/L in Nile tilapia. At the end of experiment after 28days, hepatic and renal damage markers (aspartate transaminase, alanine transaminase, alkaline phosphatase, urea, uric acid and creatinine), serum biochemical parameters (total proteins, albumin, cholesterol and glucose) and tissue antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and malondialdehyde) were detesrmined. The results of the current study revealed significant improvement in hepatic and renal damage markers after SP supplementation in fish exposed to DZN toxicity. Moreover, SP improved serum biochemical markers through increasing serum albumin and globulins with a significant decrease in serum glucose and cholesterol. In addition, liver, kidneys and gills antioxidant status showed a significant improvement after SP supplemented to fish exposed to DZN where a significant increase in tissue antioxidant activity were observed with a significant decline in lipid peroxidation levels. It can be concluded that, SP supplementation attenuated the toxic effect of DZN toxicity in Nile tilapia through improving liver and kidney functions with a significant enhancement of tissue antioxidant status.


Assuntos
Antioxidantes , Ciclídeos/metabolismo , Diazinon/toxicidade , Inseticidas/toxicidade , Spirulina , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Creatinina/metabolismo , Dieta , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Glutationa/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Ureia/metabolismo , Ácido Úrico/metabolismo
18.
Vector Borne Zoonotic Dis ; 16(11): 722-727, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27710208

RESUMO

BACKGROUND: Alkhumra hemorrhagic fever virus (AHFV) is a flavivirus that was discovered in 1995 in Saudi Arabia. Clinical manifestations of AHFV infection include hemorrhagic fever, hepatitis, and encephalitis with a reported mortality rate as high as 25%. There are no published data on the growth characteristics of AHFV in mammalian cell lines. The objective of this study was to examine the ability of AHFV to grow and propagate in four of the commonly used mammalian cell culture lines and to determine the virus growth curve characteristics in each. MATERIALS AND METHODS: Human epidermoid carcinoma (HEp-2), LLC-MK2, Madin-Darby canine kidney (MDCK), and Vero cell lines were inoculated with AHFV. The virus production by each cell line was determined by growth curve studies. Mean titers were calculated and expressed as median tissue culture infective dose per mL (TCID50/mL). RESULTS: AHFV grew and propagated to variable titers in the employed cell lines. The highest mean titers were observed in the LLC-MK2, followed by the MDCK, Vero, and HEP-2, in descending order. CONCLUSIONS: The growth curve studies showed that AHFV can propagate in the four types of cell lines to variable titers. LLC-MK2 cells are superior to MDCK, Vero, and HEP-2 for propagation of AHFV.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/fisiologia , Cultura de Vírus/métodos , Replicação Viral/fisiologia , Animais , Linhagem Celular , Chlorocebus aethiops , Efeito Citopatogênico Viral/fisiologia , Cães , Humanos
19.
Biomed Pharmacother ; 77: 79-85, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26796269

RESUMO

Spirulina platensis (SP); a microalga with high antioxidant and anti-inflammatory activities, acts as a food supplement in human and as many animal species. Deltamethrin (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to DLM leads to hepatotoxic, nephrotoxic and neurotoxic side effects for human and many species, including birds and fish. The present study was undertaken to examine the potential hepatoprotective, nephroprotective, neuroprotective and antioxidant effects of SP against sub-acute DLM toxicity in male mice. DLM intoxicated animals revealed a significant increase in serum hepatic and renal injury biomarkers as well as TNF-α level and AChE activity. Moreover, liver, kidney and brain lipid peroxidation and oxidative stress markers were altered due to DLM toxicity. Spirulina normalized the altered serum levels of AST, ALT, APL, LDH, γ-GT, cholesterol, uric acid, urea, creatinine AChE and TNF-α. Furthermore, it reduced DLM-induced tissue lipid peroxidation, nitric oxide and oxidative stress in a dose-dependent manner. Collectively, that Spirulina supplementation could overcome DLM-induced hepatotoxicty, nephrotoxicity and neurotoxicity by abolishing oxidative tissue injuries.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Nitrilas/toxicidade , Piretrinas/toxicidade , Spirulina , Acetilcolinesterase/biossíntese , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Suplementos Nutricionais , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese
20.
Ecotoxicol Environ Saf ; 111: 146-52, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25450927

RESUMO

Allicin, the main biologically active component of garlic clove extracts, has been evaluated for its' efficacy in preventing deltamethrin-induced oxidative damage in Nile tilapia; Oreochromis niloticus. Fish were fed on 2 different doses of 0.5 g and 1 g of allicin/kg diet for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholesterol, urea, uric acid, creatinine, total protein, albumin and globulin were estimated. Moreover, the level of malonaldehyde (MDA) was analyzed as a lipid peroxidation marker. In addition, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were analyzed as antioxidant biomarkers in liver, kidney and gills. Results show that deltamethrin subacute intoxication (1.46 µg/L for 28 days) increased serum AST, ALT, ALP, cholesterol, urea, uric acid, creatinine and tissue MDA. At the same time, serum total protein and albumin as well as tissue level of GSH, GSH-Px, SOD and CAT were reduced. Allicin supplemented diets enhanced all the altered serum biochemical parameters as well as tissues' lipid peroxidation and antioxidant biomarkers in a dose-dependent manner. The results suggest that feeding allicin can ameliorate deltamethrin-induced oxidative stress and might have some therapeutic properties to protect Nile tilapia on subacute deltamethrin toxicity.


Assuntos
Ciclídeos , Inseticidas/toxicidade , Nitrilas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Piretrinas/toxicidade , Ácidos Sulfínicos/farmacologia , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalase/metabolismo , Ciclídeos/metabolismo , Dieta , Dissulfetos , Brânquias/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo
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