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1.
Biomed Chromatogr ; 36(9): e5381, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35393721

RESUMO

This research developed and validated a highly sensitive and selective UPLC-MS/MS approach using a triple quadrupole mass spectrometer for quantifying favipiravir. Moreover, we introduced a study evaluating bioequivalence using two drugs, Favibrivix and Avigan, containing favipiravir. Lean Six Sigma verified the capacity and performance of the process. Protein precipitation extraction was utilized to extract favipiravir from the collected human matrices. We used an Acquity UPLCr BEH HILIC column and valproic acid as an internal standard. Furthermore, we conducted the procedure using an isocratic elution comprising acetonitrile and 0.005% ammonia in water (75:25, v/v), a flow rate of 0.25 ml/min, a temperature controlled at 10°C and an injection volume of 1.0 µl. Our UPLC-MS/MS process has a broad range (50-10,000 ng/ml) with a determination coefficient of 0.9980. We validated the method in line with the US Food and Drug Administration. The findings revealed that the test, Favibrivix 200 mg/tablet, and the reference, Avigan® 200 mg/tablet, were statistically bioequivalent in healthy Egyptian participants.


Assuntos
Espectrometria de Massas em Tandem , Gestão da Qualidade Total , Amidas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Humanos , Pirazinas , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Equivalência Terapêutica
2.
Biomed Chromatogr ; 36(7): e5382, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35389511

RESUMO

Dabigatran etexilate mesylate (DABE), a prodrug, quickly changes into dabigatran (DAB) after its oral administration. Accordingly, detecting DABE in plasma is practically unmanageable. An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to compute free DAB in participants. For the first time, the central composite design, a type of response surface methodology, was applied for optimizing variables affecting the cleavage of glucuronide bond. In addition, the pharmacokinetic parameters of generic medication (okanadab) were determined, and the obtained outcomes were compared with those of the branded drug (pradaxa). The sample preparation was done using methanol as a protein precipitant and the separation was achieved using an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm). The elution was isocratically conducted using 10 mM ammonium formate:methanol (72:28, v/v) as a mobile phase and the flow rate was 0.25 mL/min. Multiple reaction monitoring and positive electrospray ionization were used. The determination was performed within 1 min, and the calibration growth curve was established over a range of 1.19-475 ng/mL using DAB-d3 as a tagged internal standard. Bioequivalence research was validated following the US Food and Drug Administration (US FDA) guidelines for bioanalytical procedures and acceptable outcomes were achieved. The outcomes for okanadab and pradaxa did not differ significantly.


Assuntos
Dabigatrana , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Humanos , Metanol , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Equivalência Terapêutica
3.
Molecules ; 27(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35408684

RESUMO

As a continuation of our earlier work against SARS-CoV-2, seven FDA-approved drugs were designated as the best SARS-CoV-2 nsp16-nsp10 2'-o-methyltransferase (2'OMTase) inhibitors through 3009 compounds. The in silico inhibitory potential of the examined compounds against SARS-CoV-2 nsp16-nsp10 2'-o-methyltransferase (PDB ID: (6W4H) was conducted through a multi-step screening approach. At the beginning, molecular fingerprints experiment with SAM (S-Adenosylmethionine), the co-crystallized ligand of the targeted enzyme, unveiled the resemblance of 147 drugs. Then, a structural similarity experiment recommended 26 compounds. Therefore, the 26 compounds were docked against 2'OMTase to reveal the potential inhibitory effect of seven promising compounds (Protirelin, (1187), Calcium folinate (1913), Raltegravir (1995), Regadenoson (2176), Ertapenem (2396), Methylergometrine (2532), and Thiamine pyrophosphate hydrochloride (2612)). Out of the docked ligands, Ertapenem (2396) showed an ideal binding mode like that of the co-crystallized ligand (SAM). It occupied all sub-pockets of the active site and bound the crucial amino acids. Accordingly, some MD simulation experiments (RMSD, RMSF, Rg, SASA, and H-bonding) have been conducted for the 2'OMTase-Ertapenem complex over 100 ns. The performed MD experiments verified the correct binding mode of Ertapenem against 2'OMTase exhibiting low energy and optimal dynamics. Finally, MM-PBSA studies indicated that Ertapenem bonded advantageously to the targeted protein with a free energy value of -43 KJ/mol. Furthermore, the binding free energy analysis revealed the essential amino acids of 2'OMTase that served positively to the binding. The achieved results bring hope to find a treatment for COVID-19 via in vitro and in vivo studies for the pointed compounds.


Assuntos
Metiltransferases , SARS-CoV-2 , Proteínas não Estruturais Virais , Proteínas Virais Reguladoras e Acessórias , Ertapenem/farmacologia , Ligantes , Metiltransferases/antagonistas & inibidores , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , S-Adenosilmetionina/química , SARS-CoV-2/efeitos dos fármacos , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas Virais Reguladoras e Acessórias/antagonistas & inibidores
4.
Bioorg Chem ; 94: 103364, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31668461

RESUMO

Replacement of the n-butylphenyl moiety in the lipophilic part of the previously reported arylthiazole antibiotics with naphthyl ring amended its activity against vancomycin resistant strains of Staphylococcus aureus. Incorporation of the CN linker connecting the nitrogenous head with thiazole within an oxadiazole ring provided orally available analogs with relatively long half-life. In this article, a set of new twenty-three derivatives of 2-(thiazol-5-yl)-1,3,4-oxadiazole was synthesized combining both structural modifications in one new scaffold with the objectives of enhancing both the pharmacokinetic profile and antibacterial activities vs. malicious microbes. Among the synthesized new compounds, five derivatives showed promising activity with MIC values ranging from 1.95 to 3.90 µg/mL. The guanidinyl-containing naphthylthiazole and N-methylpiperazinyl derivatives (25 &29) were found equipotent as vancomycin against MRSA (2658 RCMB). The other three derivatives (23, 24 and 26) revealed 50% of vancomycin activity.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Oxidiazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Relação Estrutura-Atividade
5.
Lupus ; 27(5): 780-787, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29308728

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which affects all aspects of quality of life (QoL) of the patients. Comprehensive patient assessment should include QoL measures in addition to the objective clinical measures of the disease. There is no specific Arabic instrument for assessment of QoL of SLE patients. The objective of this study was to translate and cross culturally adapt the SLEQOL questionnaire into Arabic and test its reliability and validity. The SLEQOL questionnaire was translated into Arabic based on the Guidelines for Translation and Cross-cultural Adaptation into other languages. Reliability was assessed by interviewing patients three times: two interviews on the same day by different interviewers and the third interview 14 days later by one of the first interviewers. Validity was assessed by correlating SLEQOL scores of 91 patients with 36-item Short Form Health Survey (SF-36) scores and clinical parameters of the patients. We found that the Arabic version of SLEQOL has a Cronbach's alpha of 0.936, interobserver and intraobserver correlation coefficients of 0.809 and 0.886 respectively. Strong correlations were also found between SLEQOL scores and SF-36 Physical and Mental Component summaries. In conclusion, the Arabic version of SLEQOL is a reliable and valid instrument for measuring QoL of Egyptian SLE patients.


Assuntos
Árabes/psicologia , Lúpus Eritematoso Sistêmico/diagnóstico , Qualidade de Vida , Inquéritos e Questionários , Tradução , Adolescente , Adulto , Características Culturais , Egito/epidemiologia , Feminino , Humanos , Entrevistas como Assunto , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
6.
Child Care Health Dev ; 42(3): 394-401, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27004968

RESUMO

BACKGROUND: The early childhood period is considered the most important developmental phase in an individual's lifespan. However, it is not addressed in the Egyptian health system. We aimed to explore mothers' and healthcare providers' perceptions about early childhood development (ECD) and identify their needs to support ECD in Egypt. METHODS: Focus group discussions with 79 mothers of children younger than 2 years old from different socio-economic backgrounds and residing in urban and rural areas and 26 primary healthcare providers were used to collect data. Emerging themes and subthemes were identified from the data analysis. RESULTS: Urban and rural mothers in Egypt of all educational levels are not well prepared to support their children's early development, especially the cognitive and emotional aspects. Limited sources of information about ECD, the large families of rural women and an absence of developmental health services and family support were the most important factors that led to a neglect of mother-child communication and stimulation. CONCLUSION: Raising community awareness and training primary healthcare providers to counsel mothers about ECD are important prerequisites for supporting ECD in Egypt. Rural and first-time mothers would be the most valuable starting point.


Assuntos
Desenvolvimento Infantil/fisiologia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Comportamento Materno/psicologia , Relações Mãe-Filho/psicologia , Mães/psicologia , Poder Familiar/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Escolaridade , Egito , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Comportamento Materno/etnologia , Relações Mãe-Filho/etnologia , Mães/educação , Poder Familiar/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Pesquisa Qualitativa , População Rural , Apoio Social , Fatores Socioeconômicos , População Urbana , Adulto Jovem
7.
Parasitology ; 142(8): 1063-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25823556

RESUMO

A new name Sarcocystis chloropusae is proposed for a parasite previously found in two of 25 common moorhen (Gallinula chloropus) from Brolos Lake, Egypt. Sarcocysts were microscopic, up to 650 µm long, the cyst wall was up to 4.5 µm thick, and contained villar protrusions that were up to 4 µm long and up to 2 µm wide. The villar protrusions were crowded, contained vesicles but lacked microtubules. The ground substance layer was smooth. The bradyzoites were up to 12 µm long and up to 2 µm wide. Molecular characterization and phylogenetic analysis of the (ITS-1) supported the conclusion that the Sarcocystis in G. chloropus is a distinct species.


Assuntos
Doenças das Aves/parasitologia , Sarcocystis/classificação , Sarcocistose/veterinária , Animais , Sequência de Bases , Doenças das Aves/epidemiologia , Aves , DNA de Protozoário/química , DNA de Protozoário/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Egito , Lagos , Microscopia Eletrônica de Transmissão/veterinária , Dados de Sequência Molecular , Filogenia , Sarcocystis/genética , Sarcocystis/isolamento & purificação , Sarcocystis/ultraestrutura , Sarcocistose/epidemiologia , Sarcocistose/parasitologia , Análise de Sequência de DNA/veterinária
8.
Mymensingh Med J ; 23(1): 130-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24584386

RESUMO

"Laparoscopic assisted appendicectomy" refers to visualization of abdominal cavity, identification of appendix, drawing the appendix out through the port wound and appendicectomy. The objective of this study is to evaluate the outcome of the procedure of laparoscopic assisted appendicectomy. In this prospective study patients with appendicitis were randomly selected for laparoscopic assisted appendicectomy from August 2007 to February 2009 in the Department of Surgery, Modernized District Hospital, Joypurhat, Bangladesh. Out of 73 patients Laparoscopic assisted appendicectomy was performed successfully in 95.89% cases and conversion rate was 4.11%. Male to female ratio was almost 1:2 with mean±SD age 18.62±9.16 years. The wound infection rate was 8.2% and urinary retention 2.7%. Early postoperative feeding was started within 24 hours in 86.3% cases and mean duration of hospital stay was 2 days in 76.71% patients. More than 82% returned to their home and started social activities within 5 days. Duration of surgery was almost similar in emergency and interval appendicectomy group (19.35±10.13 vs. 23.66±9.43) minutes. Postoperative morbidity in emergency appendicectomy group showed significantly higher morbidity than interval appendicectomy group (p=0.003). This study indicates that the laparoscopic assisted appendicectomy is feasible for the majority of the patients with appendicitis in both emergency and interval settings. It reduces the operative time, shortens hospital stay and helps in early resumption of normal activities with good cosmetic outcome and patients' satisfaction.


Assuntos
Apendicectomia/métodos , Apendicite/cirurgia , Laparoscopia/métodos , Adolescente , Bangladesh/epidemiologia , Feminino , Hospitais de Distrito , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Resultado do Tratamento
9.
Eur Rev Med Pharmacol Sci ; 27(22): 10815-10830, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38039010

RESUMO

OBJECTIVE: This study aims to explore underlying molecular variations in the expression of miRNAs in kidney tissues of ginger-treated and non-treated cyclophosphamide (CP)-intoxicated rats. MATERIALS AND METHODS:   A total of 40 adult male Wistar rats were randomly divided into four groups of 10 each: Group I (control: received normal food and water), Group II (received ginger at a dose of 300 mg/kg), Group III (received CP 75 mg/kg, i.p.), and Group IV (received the same dose of CP and ginger extract).  Rats received a single injection of 75 mg/kg CP on days 3, 4, 5, 19, 20, and 21. In CP-intoxicated rats, the treatment with ginger extract at a dose of 300 mg/kg was received by oral gavage starting seven days before CP and continuing throughout the duration of the experiment for four weeks. Molecular variations in the expression of miRNAs, apoptotic genes, histological kidney damage, and abnormal kidney function in control, ginger, and CP-intoxicated rats were identified by using real-time RT-PCR Analysis, immunohistochemical, and colorimetric assays. In addition, HPLC analysis and liquid chromatography spectrophotometry analysis using Diphenyl-1-picrylhydrazyl (DPPH) radical, and Β-Carotene-linoleic acid reagents were applied respectively for in-vitro screening of phytoconstituents and antioxidant activity for ginger extract. RESULTS: The kidney tissues of CP-intoxicated rats displayed an increase in lipid peroxidation marker malonaldehyde (MDA), DNA damage, and fibrosis markers like hyaluronic acid (HA) and hydroxyproline Hypx) with a decrease in the superoxide dismutase (SOD) and total antioxidant capacity (TAC). In addition, molecular expressions of mRNA fibrotic genes such as collagen, type 1, alpha 1 (COL1A1), and α-smooth muscle actin (αSMA). Molecular expressions of levels of B-cell lymphoma 2 (BCl-2) mRNA gene were down-regulated, and the expression of mRNA apoptotic; BCL2 associated X gene (Bax), caspase-3, Bax/BCl-2 ratio genes were significantly up-regulated respectively. Moreover, cellular oxidative genes, erythroid 2-related factor (Nrf2), and heme oxygenase-1 (HO-1) were down-regulated, respectively. The miR-155-5p, miR-34a-5p, miR-21-5p significantly increased while the miR-193b-3p, miR-455-3p, and miR-342-3p significantly decreased. Ginger also increased the expression of Nrf2, HO-1, and BCl-2 genes in the kidneys of rats induced with CP. In addition, active phytoconstituents, particularly 6]]-shogaol and 6]]-gingerol, were significantly identified in ginger extract using HPLC analysis. Antioxidant activity of these active metabolites were shown to be higher against in vitro free radicals (DPPH and Β-Carotene-linoleic acid), suggesting the potential antioxidant and antiapoptotic properties of ginger against CP-toxicity. CONCLUSIONS: Treatment with ginger in rats induced with CP resulted in significant improvement in the expression of certain molecular miRNAs. The kidney tissues of these rats showed a marked decrease in the expression of miR-155-5p, miR-34a-5p, and miR-21-5p, while the levels of miR-193b-3p, miR-455-3p, and miR-342-3p were observed to increase significantly. In conclusion, ginger can protect rats from CP-induced nephrotoxicity.


Assuntos
MicroRNA Circulante , MicroRNAs , Ratos , Masculino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ratos Wistar , MicroRNA Circulante/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ácido Linoleico/metabolismo , beta Caroteno/metabolismo , Ciclofosfamida/toxicidade , Rim/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores/metabolismo , RNA Mensageiro/metabolismo
10.
Mymensingh Med J ; 21(3): 485-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22828548

RESUMO

Day case surgery offers convenience to the patients and cost saving to the healthcare institutes. In this prospective study, the authors reviewed their experience with day case Laparoscopic Cholecystectomy (LC) to determine its outcome in the government healthcare settings of Bangladesh. Selection criteria's for the day case LC were patients with symptomatic cholelithiasis with ASA (American Society of anesthesiologists) grade I or II, the availability of a responsible carer, absence of morbid obesity, low risk for concomitant presence of bile duct stones and domicile within Dhaka and around. Patients were admitted in the post operative ward as day case (DC) in the morning and were discharged on the next morning with a standard analgesia. Two hundred ten patients were admitted for LC as day cases over the last 7 years from October 2003 to October 2010 on the morning operation theatre lists. Five patients later required admission to the inpatient department for conversion to the open procedure. None of the patients was readmitted after discharge. Majority patients were followed up after 1st and 6th week. Two hundred seven patients attended for the follow up at the 1st week and 158 patients were reported for the 6th week. One hundred ninety six patients resumed their normal job or activities after one week. Patient's satisfaction was assessed by questionnaires. Two hundred five patients were either satisfied or very satisfied with the day-case procedure. It appears that for selected groups of patients, day-case LC can be safely done in government healthcare settings of Bangladesh with good patient satisfaction.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Colecistectomia Laparoscópica , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 271: 120897, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35066444

RESUMO

Nowadays, the analytical community is focusing on developing new analytical methods that incorporate principles of green analytical chemistry to reduce adverse impacts on the environment and humans. In this study, we focused specifically on establishing a correlated connection between theoretical and experimental applications via developing green, and eco-friendly visible spectrophotometric methods. These methods were relied on charge-transfer complexation (CTC) between ledipasvir and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), or chloranilic acid (CA) for sensitive colorimetric analysis of ledipasvir in the presence of sofosbuvir (Sofolanork plus®). The results were evaluated as modern computational chemistry using molecular modeling technology. At ambient temperature, the reactions for DDQ and CA took 15 and 10 min, respectively, to produce a purple red-colored solution with DDQ absorbing maximally at 588 nm and a purple-colored solution with CA absorbing maximally at 522 nm. Linearity was achieved for ledipasvir utilizing DDQ and CA in the concentration ranges of 8-80 µg.mL-1 and 40-400 µg.mL-1, respectively. The precision and accuracy of the methods mentioned were determined. Finally, the results were statistically compared to a previously published spectrophotometric technique, and no significant differences were found.


Assuntos
Antivirais , Preparações Farmacêuticas , Colorimetria , Humanos , Sofosbuvir , Espectrofotometria/métodos
12.
Food Chem ; 385: 132668, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35290954

RESUMO

In this work, carbon paste electrode (CPE) and modified CPE with copper oxide or copper yttrium oxide were prepared for determining amprolium hydrochloride (AMP) by differential pulse voltammetry. AMP has an antiprotozoal activity for treating coccidiosis in poultry; their retaining- in sheep meat and livers- induces adversative effects for the customer. XRD pattern was employed to define the fabricated nanostructured materials; the elemental composition of the nanocomposite was examined using EDX spectra. Over a pH ranging from 2 to 8, the oxidation process of AMP was studied using phosphate buffer. The scan rates were studied over a wide range (20 to 140 mV s-1) using cyclic voltammetry. The developed sensor shows a wide linear range (1.0 × 10-8-1.0 × 10-3 M) with a detection limit of 2.32 × 10-9 M. This method can quantify AMP in pharmaceutical form, sheep meat, and liver samples.


Assuntos
Cobre , Nanocompostos , Monofosfato de Adenosina , Amprólio , Animais , Carbono/química , Cobre/química , Técnicas Eletroquímicas/métodos , Eletrodos , Limite de Detecção , Fígado , Carne , Ovinos
13.
Metabolites ; 12(11)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36422263

RESUMO

Four compounds, hippacine, 4,2'-dihydroxy-4'-methoxychalcone, 2',5'-dihydroxy-4-methoxychalcone, and wighteone, were selected from 4924 African natural metabolites as potential inhibitors against SARS-CoV-2 papain-like protease (PLpro, PDB ID: 3E9S). A multi-phased in silico approach was employed to select the most similar metabolites to the co-crystallized ligand (TTT) of the PLpro through molecular fingerprints and structural similarity studies. Followingly, to examine the binding of the selected metabolites with the PLpro (molecular docking. Further, to confirm this binding through molecular dynamics simulations. Finally, in silico ADMET and toxicity studies were carried out to prefer the most convenient compounds and their drug-likeness. The obtained results could be a weapon in the battle against COVID-19 via more in vitro and in vivo studies.

14.
Clin Exp Immunol ; 159(2): 185-98, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19912257

RESUMO

Several negative regulatory mechanisms control Toll-like receptor (TLR)-mediated inflammatory responses and restore immune system balance, including the zinc-finger protein A20, a negative regulator of TLR signalling that inhibits nuclear factor kappa B (NF-kappaB) activity. In the present study, we investigated TLR-5-mediated A20 expression and its role in intestinal epithelial cells (IECs) during inflammation. HCT-15 and HT-29 cells were stimulated with flagellin, then the expressions of A20, interleukin-1 receptor-associated kinase (IRAK-M) and Tollip were evaluated using RNase protection assay. Furthermore, experimental colitis was induced in tlr4-deficient CH3/HeJ mice by administration of dextran sodium sulphate (DSS), then flagellin was injected anally, and the colonic expression of A20 was examined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To confirm flagellin-induced expression of A20, we employed an organ culture system. The role of A20 in flagellin-induced tolerance induction was evaluated in vitro, using a gene knock-down method targeting A20. A20 expression increased rapidly and peaked at 1 h after flagellin stimulation in cultured IECs, then declined gradually to the basal level. In vivo, anal injection of flagellin induced epithelial expression of A20 in injured colonic tissue, whereas flagellin did not cause a significant increase in A20 expression in non-injured normal tissue, which was also confirmed in vitro using the organ culture system. Gene knock-down using A20 siRNA did not influence tolerance induced by restimulation with flagellin. A20 is an early response negative regulator of TLR-5 signalling in IECs that functions during intestinal inflammation. Our results provide new insights into the negative feedback regulation of TLR-5 signalling that maintains the innate immune system in the gut.


Assuntos
Células Epiteliais/metabolismo , Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Receptor 5 Toll-Like/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Proteínas de Ligação a DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Flagelina/administração & dosagem , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Imuno-Histoquímica , Inflamação/patologia , Intestinos/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipopolissacarídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Proteínas Nucleares/genética , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa
15.
Clin Exp Immunol ; 162(2): 348-61, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21077278

RESUMO

Single immunoglobulin (Ig) interleukin-1R-related molecule (SIGIRR) is an Ig-like membrane protein critical for negative regulation of Toll-like receptor (TLR)-4-mediated signalling. We investigated SIGIRR expression and its regulation mechanism in intestinal epithelial cells (IECs) during inflammation. Endoscopic biopsy specimens were obtained from active and inactive colonic mucosa of ulcerative colitis (UC) patients, then SIGIRR expression was examined using real-time polymerase chain reaction (PCR) and immunohistochemistry (IH). Mice experimental colitis models were established by administrations of sulphonic acid (TNBS) and dextran sodium sulphate (DSS), and epithelial expression of SIGIRR was examined using real-time PCR, IH and flow cytometry. The effects of lipopolysaccharide (LPS) and tumour necrosis factor (TNF)-α on SIGIRR expression were evaluated in vitro using cultured IECs. To elucidate SIGIRR expression regulation in IECs, binding ability of the transcription factor SP1 at the responsive element of the SIGIRR promoter was examined using gel-shift and chromatin immunoprecipitation (ChIP) assays. In human colonic samples, SIGIRR was expressed mainly in IECs at levels significantly higher in inactive compared to active mucosa. In the mice, SIGIRR colonic expression decreased rapidly after colitis development and returned gradually to basal levels. Experimental colitis-mediated down-regulation of SIGIRR in IECs was also confirmed by IH and flow cytometry results. Further, inflammatory conditions induced by TLR ligands and TNF-α caused significant down-regulation of SIGIRR expression in IECs, which was dependent upon decreased SP1 binding at the responsive element of the SIGIRR promoter. We found that SIGIRR is expressed in IECs and serves as a negative regulator to maintain gut innate immunity, which is down-regulated during inflammation by inhibition of an SP1-mediated pathway.


Assuntos
Colite/metabolismo , Regulação para Baixo/imunologia , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Receptores de Interleucina-1/metabolismo , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Colite/induzido quimicamente , Colite Ulcerativa/metabolismo , Colo/metabolismo , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Humanos , Inflamação/metabolismo , Intestino Grosso/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , RNA Interferente Pequeno/genética , Receptores de Interleucina-1/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Fator de Transcrição Sp1/metabolismo , Organismos Livres de Patógenos Específicos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia , Adulto Jovem
16.
Nanotechnology ; 21(50): 505303, 2010 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-21098935

RESUMO

Previous reports have detailed the fabrication of media able to support high density magnetic recording in both longitudinal and perpendicular formats by the global rapid thermal processing of sputtered non-magnetic precursor films. During processing in this manner a magnetic element is released from its nitride and agglomerates to form a random near mono-dispersion of magnetic nano-particles. Here we explore, primarily through modelling and simulation, the feasibility of processing similarly formulated precursor media not globally but locally. We investigate the potential of using conducting nano-probe tips to produce, via electro-thermal (Joule) heating, a nano-patterned recording medium in the form of regular arrays of magnetic islands in a non-magnetic host. In the first instance we concentrate on the simplest cobalt based precursor medium for which both initial simulation and experimental studies indicate the formation of magnetic islands with dimensions of the order of the tip diameter; this is relatively straightforward. The results signify that if practical production scenarios can be devised to produce technologically significant areas of recording media by the rapid multi-probe repetition of this technique, then processing in this manner offers a promising route to areal recording densities of perhaps 5 Terabit/in(2) even with the simplest cobalt media. We also note that the electro-thermal processing method is potentially extendable to the production of a wide variety of magnetic materials (e.g. PtCo, FeCo, NiFe alloys) and, applied via electrical nano-imprinting type techniques, to the production of a wide variety of patterned structures.

17.
Mymensingh Med J ; 19(1): 77-84, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20046176

RESUMO

Laparoscopic cholecystectomy is accepted as the procedure of choice for gallstone diseases but like all other procedure it is also not free from unwanted events. In this study, the authors have analyzed their experience in laparoscopic cholecystectomy (LC) and its complications and their management. Amongst the total 4957 laparoscopic cholecystectomy (LC) performed by the authors between April 1995 to May 2005 the male, female ratio was 1:5.6 (744 and 4213). 15.33%(760) of LC were carried out for the patients with acute cholecystitis. The age ranged from 9 years to 98 years. Mean operating time was 37 minutes (7 m to 187 m). Average hospital stay was 2.23 days (20 h to 7d). Peri-cholecystic adhesions including cholecysto-enteric fistulae and acute inflammation were the main reason for difficult dissection. This could be anticipated from the history of recurrent attack, high fever, severe pain and thick walled gall bladder (GB) on ultrasonography (USG). The main per-operative problem the authors came across was hemorrhage 5.2%(258), iatrogenic perforation of the gallbladder 15.12%(755) and common bile duct (CBD) injuries 0.12%(7). Conversion to open procedure was necessary in 0.68%(36) cases, most commonly due to obscure anatomy as a result of chronic inflammatory adhesions 0.56%(28), the other reasons for conversion were to deal with the CBD injury 0.04%(2), cholecysto-colic fistula 0.02%(1), unsuspected malignancy 0.06%(3) and uncontrolled bleeding 0.04%(2). The postoperative complications were port site infection and stitch granuloma 0.75%(37), bile leakage 0.08%(4), hemorrhage 0.06%(3), sub-hepatic abscess 0.02%(1), peritonitis due to gut perforation 0.04%(2) and retained bile duct stones 0.06%(3). Two deaths were due to septicemia resulting from gut perforation. Laparoscopic cholecystectomy is a safe procedure in the hands of a surgeon with adequate exposure to open surgery and properly oriented in minimally invasive surgery. Complications can be reduced to minimum if meticulous principle of dissection is followed. The unwanted events can mostly be managed laparoscopically without conversion. But decision for conversion should be taken early if there is any confusion and thus mortality and morbidity could be minimized.


Assuntos
Colecistectomia Laparoscópica , Doenças da Vesícula Biliar/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colecistectomia Laparoscópica/efeitos adversos , Estudos de Coortes , Feminino , Doenças da Vesícula Biliar/etiologia , Doenças da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Mymensingh Med J ; 19(3): 442-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20639842

RESUMO

Two patients (one male and one female) underwent endoscopic para-thyroidectomy for parathyroid adenoma at the Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Three ports (one mid line and two laterals) were employed, a 10 mm telescope was used for the visualization and a harmonic scalpel was used for the dissection. To the best of our knowledge, there was no report of endoscopic para-thyroidectomy from Bangladesh. Both patients were fed on the first post operative day and discharged from the 4th and 8th operative day. Both patient's parathyroid hormone (PTH) level dropped to about one fourth the level in 12 to 20 minutes after enucleation (as compared to the immediate pre operative level). Endoscopic para-thyroidectomy appears to be a technically feasible patient friendly modality of treatment for the selected cases of para-thyroid pathology in experienced hand with excellent cosmetic outcome.


Assuntos
Adenoma/cirurgia , Endoscopia/métodos , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/instrumentação , Adenoma/patologia , Bangladesh , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/patologia
19.
Scand J Gastroenterol ; 44(2): 172-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18830898

RESUMO

OBJECTIVE: CD5(+) B cells comprise a unique subset of B cells that modulates innate as well as autoimmune systems. The aim of this study was to investigate alterations of the circulating CD5(+) B-cell subset in patients with inflammatory bowel disease (IBD) by evaluating various clinical parameters, including therapeutic regimens. MATERIAL AND METHODS: Thirty-four patients with ulcerative colitis (UC), 19 patients with Crohn's disease (CD), and 46 healthy control subjects were enrolled in this study. CD5(+) B cells in peripheral blood collected from each subject were analyzed by flow cytometry. Multiple regression analysis was carried out to evaluate the factors related to the circulating CD5(+) B-cell subset in the IBD patients. In an in vitro examination, dexamethasone-induced apoptosis in peripheral blood B cells was examined by detecting cell surface binding of the annexin-V antibody. RESULTS: Age and gender in the control subjects did not influence the circulating CD5(+) B-cell subset. Multiple regression analysis showed that the presence of UC, corticosteroid therapy, and number of white blood cells in peripheral blood each had a significant influence in decreasing the number of circulating CD5(+) B cells in the IBD patients. Furthermore, in vitro results showed that dexamethasone treatment significantly induced apoptosis in CD5(+) B cells, though apoptosis was similarly observed in CD5(-) B cells. CONCLUSIONS: CD5(+) B cells may be involved in the pathogenesis of UC, and modulation of this subset by corticosteroid therapy may play a role in the treatment of IBD patients.


Assuntos
Subpopulações de Linfócitos B/metabolismo , Linfócitos B/metabolismo , Antígenos CD5/sangue , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Adolescente , Adulto , Idoso , Antígenos CD5/imunologia , Estudos de Casos e Controles , Feminino , Glucocorticoides/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 206: 302-313, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30125819

RESUMO

A highly accurate and precise spectrofluorimetric method was established for quantitation of Gatifloxacin in pure material, pharmaceutical formulations and in the existence of its oxidative degradation product. The emission was recorded at 487 nm after the excitation at 290 nm. Using micelle, sodium dodecyl sulphate (SDS), enhanced fluorescence intensity of Gatifloxacin-SDS complex. The optimization of numerous experimental conditions was carried out. The improved emission showed a suitable linear correlation between derivative synchronous fluorescence power and concentration of Gatifloxacin over the range of 10 to 100 ng/mL with a determination coefficient equals 0.9996. Studying cytotoxicity and antimicrobial susceptibility for oxidative degradation product of Gatifloxacin was carried out using Gatifloxacin as a control. In comparison, the proposed method presented a superior sensitivity and enhanced stability over the reported method.


Assuntos
Gatifloxacina/análise , Espectrometria de Fluorescência/métodos , Bactérias/efeitos dos fármacos , Estabilidade de Medicamentos , Gatifloxacina/química , Gatifloxacina/farmacologia , Limite de Detecção , Modelos Lineares , Testes de Sensibilidade Microbiana , Oxirredução , Comprimidos
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