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1.
Int J Pharm ; 663: 124541, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39089344

RESUMO

Although the use of thermoplastic polyurethane (Tpu) nanofiber mats as wound dressings is of great interest due to their mechanical properties, they are hindered by their poor wettability and bioavailability. In this study, we aimed to improve the cellular affinity of Tpu nanofiber mats for skin disorders by incorporating extracted collagen (Col) from tendons and physically mixed with a layer of phytoceramides (Phyto) to produce TpuCol@X-Phyto mats in which the weight % of Phyto relatively to the weight of the solution was X = 0.5, 1.0, or 1.5 wt% via facile electrospinning approach. The collective observations strongly indicate the successful incorporation and retention of Phyto within the TpuCol architecture. An increase in the Phyto concentration decreased the water contact angle from 69.4° ± 3.47° to 57.9° ± 2.89°, demonstrating improvement in the hydrophilicity of Tpu and binary blend TpuCol nanofiber mats. The mechanical property of 1.0 wt% Phyto aligns with practical requirements owing to the presence of two hydroxyl groups and the amide linkage likely contributing to various hydrogen bonds, providing mechanical strength to the channel structure and a degree of rigidity essential for transmitting mechanical stress. The proliferation of human skin fibroblast (HSF) peaked significantly 100 % with TpuCol@X-Phyto mats coated for X =1.0 and 1.5 wt% of Phyto. Electrospun scaffolds with the highest Phyto content have shown the lowest degree of hemolysis, demonstrating the high level of compatibility between them and blood. The TpuCol@1.5Phyto mat also demonstrated higher efficacy in antibacterial and antioxidant activities, achieving a rate of DPPH radical scavenging of 83.3 % for this latter property. The most notable wound closure among all tested formulations was attributed to higher Phyto. Thus, the developed TpuCol@1.5Phyto nanofiber formula exhibited enhanced healing in an in vitro epidermal model.


Assuntos
Colágeno , Nanofibras , Poliuretanos , Nanofibras/química , Poliuretanos/química , Humanos , Colágeno/química , Dermatopatias/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Fibroblastos/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bandagens , Cicatrização/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas
2.
Expert Rev Anticancer Ther ; 24(10): 1009-1020, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39138591

RESUMO

BACKGROUND: Genetic polymorphisms play a crucial role in predicting treatment efficacy in patients with hepatocellular carcinoma (HCC). This study aims to evaluate the response to Transarterial Chemoembolization (TACE) in relation to the genetic polymorphisms of interleukin 28B (IL28B) and angiopoietin-2 (ANGPT2) in HCC patients. RESEARCH DESIGN AND METHODS: Prospective cohort study conducted on 104 eligible HCC Egyptian patients who underwent TACE using doxorubicin and lipiodol. Genotyping of the IL28B and ANGPT2 genes was performed with laboratory data analysis. RESULTS: At baseline IL28B rs12979860 genotypes C/T, C/C and T/T appeared in 43.9%, 34.6% and 21.5% while ANGPT2 rs55633437 genotypes C/C, C/A and A/A found in 71.03%, 28.04% and 0.93% of patients respectively. After one month of therapy, 51.4% of patients achieved a complete response. There was a significant difference in relation to IL28B rs12979860 genotypes (p = 0.017) whereas ANGPT2 rs55633437 genotypes (p = 0.432) showed no significant difference in patient response after one month of TACE. CONCLUSION: This study demonstrates the effectiveness of TACE in Egyptian HCC patients, as evidenced by low recurrence rates. Furthermore, the IL28B rs12979860 (C/T) gene may be associated with the efficacy and prognosis of TACE treatment in HCC Egyptian patients. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05291338).


Assuntos
Angiopoietina-2 , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Doxorrubicina , Óleo Etiodado , Genótipo , Interferons , Interleucinas , Neoplasias Hepáticas , Humanos , Quimioembolização Terapêutica/métodos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Egito , Feminino , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Pessoa de Meia-Idade , Estudos Prospectivos , Angiopoietina-2/genética , Óleo Etiodado/administração & dosagem , Estudos de Coortes , Interleucinas/genética , Interferons/administração & dosagem , Adulto , Resultado do Tratamento , Idoso , Polimorfismo de Nucleotídeo Único , Interferon lambda
3.
Inflammopharmacology ; 32(5): 3259-3269, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38985232

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn's Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD. AIM: This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD. METHOD: This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn's Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period. RESULTS: In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002). CONCLUSION: Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients. CLINICAL TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).


Assuntos
Adalimumab , Infliximab , Humanos , Infliximab/uso terapêutico , Infliximab/efeitos adversos , Infliximab/administração & dosagem , Adalimumab/uso terapêutico , Adalimumab/efeitos adversos , Adalimumab/administração & dosagem , Masculino , Feminino , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Doença de Crohn/tratamento farmacológico , Índice de Gravidade de Doença , Colite Ulcerativa/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Proteína C-Reativa/metabolismo , Adulto Jovem , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/farmacologia
4.
Pharmgenomics Pers Med ; 14: 1679-1687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992430

RESUMO

BACKGROUND: Acne vulgaris (AV) is a chronic inflammatory disease that affects the pilosebaceous unit. Leptin (LEP) gene polymorphisms is associated with higher risk of multiple disorders. Insulin-like growth factor-1 (IGF-1) exerts comedogenic effect by stimulating the sebaceous glands. Isotretinoin is an effective oral therapy for AV with many side effects including hyperlipidemia and increased serum levels of liver enzymes. PURPOSE: To evaluate the impact of LEP gene rs7799039 polymorphism in acne patients' clinical response lipid profile and liver enzymes following 6 months oral isotretinoin therapy in Egyptian AV patients. METHODS: One hundred eligible AV patients received 0.5 mg/kg oral isotretinoin for 6 months. Patients' demographics and clinical data were obtained. Body mass index (BMI), lipid profile, liver enzymes and IGF-1 were measured at baseline and after 6 months of therapy. Genotyping was done for LEP gene rs 7799039. RESULTS: Six month administration of oral isotretinoin in Egyptian AV patients is associated with significantly elevated aspartate transaminase (AST) in CC and AC genotypes (P<0.001). Significant alanine aminotransferase (ALT) elevation was observed in CC, AC and AA genotypes (P <0.001, 0.004, 0.002, respectively). Total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) were elevated significantly P<0.001) in the three genotypes. IGF-1 was decreased significantly in CC and AC genotypes (P<0.001). CC genotype is associated with highest response (P<0.001). CONCLUSION: LEP rs7799039 gene had an impact on the clinical response, lipid profile and liver enzymes in AV patients treated with oral isotretinoin. LEP rs7799039 CC genotype is predicted to be the treatment candidate for 6 month oral isotretinoin.

5.
Med Hypotheses ; 144: 110140, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32768893

RESUMO

While researchers are struggling to develop a vaccine for coronavirus disease, it is important to evolve effective therapeutic strategies to save lives. The majority of coronavirus disease deaths are due to pneumonia. Mostly, stress and depression are associated with coronavirus disease infection and thus, resulting in weakening of patients' immune response and hence, more severe respiratory symptoms or even death. We propose using a class of antidepressants named selective serotonin reuptake inhibitors for their reported potential antiviral effect, modulatory effect of respiratory symptoms, antioxidant properties and immunoregulatory effects beside their main action as antidepressant. In addition, the low cost of selective serotonin reuptake inhibitors might add a benefit for coronavirus disease patients.


Assuntos
Anti-Inflamatórios/farmacologia , Tratamento Farmacológico da COVID-19 , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Anticoagulantes/farmacologia , Antidepressivos/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Citocinas/metabolismo , Depressão/tratamento farmacológico , Humanos , Sistema Imunitário , Inflamação , Pulmão/efeitos dos fármacos , Modelos Teóricos , Risco , Serotonina/metabolismo , Sertralina/farmacologia , Estresse Psicológico
6.
Int J Clin Pharm ; 42(4): 1207-1216, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32712884

RESUMO

Background Hepatitis C virus infection is one of the major causes of liver cirrhosis and hepatocellular carcinoma worldwide. IL28B gene polymorphism has a direct relation to the response of interferon-based regimens. However, the effect of IL28B gene polymorphism on efficacy of the new direct acting antivirals used in treatment of chronic hepatitis C Egyptian patients hasn't been studied yet. Objective This study aimed to investigate the frequency of IL28B genotypes and impact of its polymorphism on the efficacy and safety of two direct acting antiviral regimens. Setting Patients were recruited form faculty of Medicine Ain shams research institute, Cairo, Egypt. Methods Easy to treat chronic hepatitis C Egyptian patients were included in this prospective study. Patients were randomized into two groups, group 1 received sofosbuvir plus daclatasvir and group 2 received paritaprevir, ombitasvir and ritonavir plus ribavirin. Both treatment regimens were given for 3 months. Laboratory evaluation and IL28B rs 12979860 genotyping were performed at baseline. Follow ups were performed monthly. Fibrosis was assessed at baseline and after treatment. Main outcome measures The frequency of IL28B genotypes and their correlation with safety and efficacy of direct acting antiviral regimens. Results CT genotype was present in 52.42% of patients while CC and TT genotypes were present in 28.16% and 19.42% of patients, respectively. IL28B genotypes weren't correlated to sustained virologic response in both treatment groups. Baseline fibroscan scores didn't show any significant relations with IL28B genotypes. Aspartate aminotransferase/alanine aminotransferase ratio increased significantly at the end of treatment in group1. CC genotype had shown higher ratio values at the end of treatment in Group 2. Conclusion CT genotype is the predominant genotype in easy to treat HCV Egyptian patients. IL28B genotypes hasn't any predictive value on the efficacy or the safety of direct acting antiviral regimens.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferons/genética , Adulto , Antivirais/efeitos adversos , Quimioterapia Combinada , Egito , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Resultado do Tratamento
7.
J Clin Pharm Ther ; 45(3): 539-546, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31889322

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Direct-acting antivirals (DAAs) have become the most widely used treatment of chronic hepatitis C infection. Comparative studies on DAAs regimens approved by the Egyptian Ministry of Health for easy-to-treat genotype 4 (G4) Egyptian patients are still deficient. In this prospective study, we compared the efficacy and cost of two DAA regimens that are used in the treatment of Egyptian chronic hepatitis C virus (HCV) G4. The cost-saving regimen is determined. METHODS: Eligible patients were randomized into 2 groups. Group 1 (Gp 1) received sofosbuvir plus daclatasvir, and group 2 (Gp 2) received ombitasvir, paritaprevir and ritonavir plus ribavirin (RBV) for 12 weeks. Data were collected and evaluated at baseline and at weeks 4, 8 and 12. Sustained virologic response 12 weeks after the end of treatment (SVR12 ) was evaluated. Cost-minimization analysis (CMA) was performed. RESULTS AND DISCUSSION: Eligibility was achieved in 107 patients, Gp1 included 57 patients, and Gp 2 included 50 patients. Two patients dropped out from Gp 2 due to non-compliance. All patients in the two groups showed negative HCV blood levels at the end of treatment. At the 24th week, 3 relapsers (5.2%) were detected in Gp1 and 2 relapsers (4.1%) were detected in Gp 2. SVR12 was 54/57 (94.7%) and 46/48 (95.8%) for Gp 1 and Gp 2, respectively. After the 12th week of treatment, a significant decrease in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and haemoglobin levels were observed in both groups. Albumin levels declined in Gp 2 only. CMA showed higher cost in Gp 2 than Gp 1, although similar efficacy and safety. WHAT IS NEW AND CONCLUSION: The two DAA regimens showed high SVR12 and safety in Egyptian HCV G4 patients. Sofosbuvir plus daclatasvir is the cost-saving regimen.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Adolescente , Adulto , Antivirais/efeitos adversos , Antivirais/economia , Análise Custo-Benefício , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Egito , Feminino , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resposta Viral Sustentada , Resultado do Tratamento , Adulto Jovem
8.
World J Gastroenterol ; 19(16): 2529-36, 2013 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-23674855

RESUMO

AIM: To evaluate the safety, efficacy and tolerability of Nigella sativa (N. sativa) in patients with hepatitis C not eligible for interferon (IFN)-α. METHODS: Thirty patients with hepatitis C virus (HCV) infection, who were not eligible for IFN/ribavirin therapy, were included in the present study. Inclusion criteria included: patients with HCV with or without cirrhosis, who had a contraindication to IFN-α therapy, or had refused or had a financial constraint to IFN-α therapy. Exclusion criteria included: patients on IFN-α therapy, infection with hepatitis B or hepatitis I virus, hepatocellular carcinoma, other malignancies, major severe illness, or treatment non-compliance. Various parameters, including clinical parameters, complete blood count, liver function, renal function, plasma glucose, total antioxidant capacity (TAC), and polymerase chain reaction, were all assessed at baseline and at the end of the study. Clinical assessment included: hepato and/or splenomegaly, jaundice, palmar erythema, flapping tremors, spider naevi, lower-limb edema, and ascites. N. sativa was administered for three successive months at a dose of (450 mg three times daily). Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. RESULTS: N. sativa administration significantly improved HCV viral load (380808.7 ± 610937 vs 147028.2 ± 475225.6, P = 0.001) and TAC (1.35 ± 0.5 vs 1.612 ± 0.56, P = 0.001). After N. sativa administration, the following laboratory parameters improved: total protein (7.1 ± 0.7 vs 7.5 ± 0.8, P = 0.001), albumin (3.5 ± 0.87 vs 3.69 ± 0.91, P = 0.008), red blood cell count (4.13 ± 0.9 vs 4.3 ± 0.9, P = 0.001), and platelet count (167.7 ± 91.2 vs 198.5 ± 103, P = 0.004). Fasting blood glucose (104.03 ± 43.42 vs 92.1 ± 31.34, P = 0.001) and postprandial blood glucose (143.67 ± 72.56 vs 112.1 ± 42.9, P = 0.001) were significantly decreased in both diabetic and non-diabetic HCV patients. Patients with lower-limb edema decreased significantly from baseline compared with after treatment [16 (53.30%) vs 7 (23.30%), P = 0.004]. Adverse drug reactions were unremarkable except for a few cases of epigastric pain and hypoglycemia that did not affect patient compliance. CONCLUSION: N. sativa administration in patients with HCV was tolerable, safe, decreased viral load, and improved oxidative stress, clinical condition and glycemic control in diabetic patients.


Assuntos
Antioxidantes/uso terapêutico , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Nigella sativa , Extratos Vegetais/uso terapêutico , Óleos de Plantas/uso terapêutico , Adulto , Antioxidantes/efeitos adversos , Antivirais/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Interações Medicamentosas , Egito , Feminino , Hepatite C/sangue , Hepatite C/diagnóstico , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Projetos Piloto , Extratos Vegetais/efeitos adversos , Óleos de Plantas/efeitos adversos , Plantas Medicinais , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Carga Viral
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