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IntroductionCorona Virus-induced disease – 2019 (COVID-19) pandemic stimulates research works to find a solution to this crisis from starting 2020 year up to now. With ending of the 2021 year, various advances in pharmacotherapy against COVID-19 have emerged.Regarding antiviral therapy, Casirivimab and imdevimab antibody combination is a type of new immunotherapy against COVID-19. Standard antiviral therapy against COVID-19 includes Remdesivir and Favipravir.Aim of StudyTo compare the efficacy and safety of antibodies cocktail (casirivimab and imdevimab), Remdesivir, and Favipravir in the COVID-19 patientsPatients and Population265 hospitalized COVID-19 patients were used to represent the COVID-19 population and were assigned into three groups in a ratio of (1:2:2) respectively, Group (A) received REGN3048-3051(Antibodies cocktail (casirivimab and imdevimab), group (B) received remdesivir, and group (C) received favipravir.MethodsThe study design is a single-blind non-Randomized Controlled Trial (non-RCT). The drugs of the study are owned by Mansoura University Hospital (MUH) and prescribed by chest diseases lectures of the faculty of medicine-Mansoura University. The duration of the study is about 6 months after ethical approval.Results and discussionCasirivimab and imdevimab achieve less 28-day mortality rate, less mortality at hospital discharge, more negative swab cases, less need for O2 therapy and IMV, less duration of this need, less hospital and ICU stay, less case progression as presented by lower World Health Organization (WHO) scale and better multi-organ functions as presented by lower Sequential Organ Function Assessment (SOFA) score than Remdesivir and Favipravir.ConclusionFrom all of these results, it is concluded that Group A (Casirivimab & imdevimab) has more favorable clinical outcomes than B (remdesivir) & C (favipravir) intervention groups.Clinical Trial Registration:NCT05502081, 16/08/2022,Clinicaltrials.gov, retrospectively registered

Sahar M El-Haggar,1 Sahar K Hegazy,1 Sherief M Abd-Elsalam,2 Eslam B Elkaeed,3 Ahmed A Al-Karmalawy,4 Mostafa M Bahaa5 1Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Gharbia Government, Tanta, 31527, Egypt; 2Tropical Medicine and Infectious Diseases Department, Faculty of Medicine, Tanta University, Tanta, 315274, Egypt; 3Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, 13713, Saudi Arabia; 4Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt; 5Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, EgyptCorrespondence: Mostafa M Bahaa, Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt, Tel +201025538337, Email mostafabahaamnf@gmail.com; mbahaa@horus.edu.egBackground and Purpose: Irritable bowel syndrome (IBS) is defined as an association of chronic abdominal pain with bowel habit abnormalities, without clear organic dysfunction. T-type calcium channels and low-grade mucosal inflammation are linked to abdominal pain; however, medical treatments for IBS abdominal pain are largely ineffective. In this study, we investigated if pentoxifylline (PTX) and ethosuximide could potentially alleviate abdominal pain in patients with IBS treated with mebeverine.Methods: We recruited 150 patients from Tanta University Hospital to this randomized, prospective, and double blinded study. Patients were randomly allocated to three groups (n = 50). Group 1 (mebeverine) received 135 mg mebeverine three times/day (t.i.d). Group 2 (ethosuximide group) received 135 mg mebeverine t.i.d plus 250 mg ethosuximide twice daily (b.i.d) and group 3 (PTX group) received 135 mg mebeverine t.i.d plus 400 mg PTX b.i.d. Patients were assessed by a gastroenterologist at baseline and 6 months after therapy. Serum interleukin-8 (IL-8), IL-6, tumor necrosis-α (TNF-α), fecal myeloperoxidase, and fecal neutrophil gelatinase associated lipocalin (NGAL) levels were measured before and after therapy. The numeric pain rating scale (NRS) was also assessed before and after therapy.Primary Outcomes: Reduced NRS scores and abdominal pain relief.Secondary Outcomes: Decreased inflammatory biomarkers.Results: After 6 months, groups 2 and 3 showed a significantly greater reduction in serum IL-8, IL-6, TNF-α, fecal myeloperoxidase, and fecal NGAL levels when compared to group 1 after therapy. Both groups 2 and 3 showed significant reductions in NRS scores when compared to the group 1.Conclusion: Ethosuximide and PTX may be promising, novel adjunct drugs to antispasmodics for relieving abdominal pain in patients with IBS.Trial Registration: Identifier: NCT04217733.Graphical Abstract: Keywords: IBS, inflammation, pentoxifylline, Ca++ channels, ethosuximide

Introduction: Corona Virus induced disease – 2019 (COVID-19) disaster motivates scientific research to find a settling to this pandemic. With ending of 2021 year, various advances in immunotherapy against COVID-19 have emerged. Regarding antiviral therapy, Casirivimab and imdevimab antibody combination is a type of new immunotherapy against COVID-19. Other antiviral therapy against COVID-19 includes Remdesivir and Favipravir. Aim of Study: To compare the efficacy and safety of casirivimab and imdevimab, Remdesivir and Favipravir as antiviral agents in hospitalized COVID19 patients. Patients and Population: 265 COVID-19 Polymerase Chain Reaction (PCR) positive patients are included in this study and will be assigned into 3 groups in a ratio of (1:2:2): 1- Group A: REGN3048-3051 2-group B: Remdesivir 3-group C: Favipravir Methods: Study design is single blind non-Randomized Controlled Trial (non-RCT). The duration of study is about 6 months after ethical approval. Results and discussion: Casirivimab and imedivimab achieves less 28-day mortality rate, less mortality at hospital discharge, more negative swab cases than Remdesivir and Favipravir. Conclusion: the results show that Group A (Casirivimab & imedivimab) achieves more favorable clinical outcomes than B (remdesivir) & C (favipravir) groups.

Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15–25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P

Objective: Endothelial dysfunction is afflicted to the maturation of arteriosclerosis and type 2 diabetes mellitus (T2DM) vascular complications. This study designed to evaluate the impact of fenofibrate adjuvant therapy on endothelial dysfunction and cardiovascular risk in patients with T2DM. Methods: Seventy-five subjects were recruited from the Internal Medicine Department of Tanta University Hospital. The participants were classified into three groups: Group 1 (control group), 25 healthy subjects; Group 2, 25 T2DM patients received glimepiride/metformin (2:500 mg/day); and Group 3, 25 T2DM patients received glimepiride/metformin (2:500 mg/day)+fenofibrate (300 mg/day). Patients were assessed before and 3 months after intervention for the determination of body mass index (BMI), blood pressure, glycemic picture (hemoglobin A1C % and homeostatic model assessment of insulin resistant), lipid panel, Castelli’s risk index (CRI-I and CRI-II), albumin-to-creatinine ratio (ACR), and endothelial dysfunction biomarkers (asymmetric dimethylarginine [ADMA] and Syndecan-1 (SDC-1)]. Data were statistically analyzed by one-way analysis of variance; p

What is known and objectives There is clear evidence for an association between irritable bowel syndrome (IBS) and visceral hypersensitivity. This clinical study aimed to assess the adjunct role of ethosuximide, an antiepileptic drug with T-type calcium channel blocking activity, in the relieving of IBS-related abdominal pain. Methods This is a prospective, 3-month, randomized and controlled study of parallel groups. Fifty outpatients who met the inclusion criteria participated in the trial. Patients were allocated randomly: 25 received mebeverine 135 mg three times daily (t.i.d), whereas the other 25 received mebeverine 135 mg t.i.d and ethosuximide 500 mg t.i.d. At baseline and 12 weeks after starting the drug, patients were evaluated by a gastroenterologist. Serum tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), faecal myeloperoxidase and faecal neutrophile gelatinase-associated lipocalin (NGAL) levels were tested before and after treatment. The Numeric Pain Rating Scale (NRS) was assessed before and after three months of therapy. Results and discussion After 12 weeks, the ethosuximide group showed a statistically and significantly greater reduction in the serum levels of TNF-α, IL-6, IL-8, faecal myeloperoxidase and faecal NGAL in comparison with the control group after the treatment. Moreover, the ethosuximide group showed a statistically significant decrease in NRS compared with the mebeverine group. What is new and conclusion Ethosuximide could be a promising adjunct to antispasmodics in the treatment of IBS patients. Trial registration identifier: NCT04217733.

Metastatic colorectal cancer (mCRC) predominantly contributes to cancer-related mortalities secondary to distant metastasis. This study aimed at investigating anti-tumor activity and safety of mebendazole in patients with mCRC.This prospective, randomized double blind placebo-controlled study enrolled 40 mCRC patients who were randomized into two groups; the control group (n = 20) which received 6 cycles of bevacizumab with FOLFOX4 plus placebo tablets BID and mebendazole group (n = 20) which received 6 cycles of bevacizumab with FOLFOX4 plus mebendazole 500 mg orally BID for 12 weeks. Computed tomography scanning and serum levels of carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), liver and renal parameters were assessed at baseline and after 12 weeks. One-year overall survival and progression free survival (PFS) were also determined. Data were analyzed using paired, independent sample-t-tests, Mann-Whitney U, Chi-Square and Kaplan-Meier tests and p 0.05 was considered statistically significant.Mebendazole was well tolerated and its addition to bevacizumab and FOLFOX4 enhanced tumor response to treatment which was translated by significant improvement of overall response rate 12 weeks after intervention [10 % (2) versus 65% (13) for control and mebendazole groups, respectively; p = 0.000] and significant elevation of PFS (median: 3 and 9.25 months for control and mebendazole groups, respectively; p = 0.000). Furthermore, mebendazole produced significant decline in VEGF level (p = 0.006) with non-significant variation in CEA level (p = 0.063).Mebendazole may represent an attractive candidate for drug repositioning against mCRC secondary to its safety and efficacy in enhancing tumor response to chemotherapy.NCT03925662, retrospectively.

The development of drug resistance remains the major obstacle to clinical efficacy of cancer chemotherapy. Consequently, finding new therapeutic options for cancerous patients is an urgent need. Sixty newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients were recruited from Clinical Oncology Department, Faculty of Medicine, Menoufia University, Egypt prospectively randomized to three groups (n = 20 for each group). Group one (control group) received R-CHOP standard chemotherapy {Rituximab, Cyclophosphamide, Hydroxyldaunorubicin (Doxorubicin)®, Vincristine (oncovin)®, prednisolone in the first five days of cycle}, group two received lansoprazole (LAN) 60 mg p.o. bid for only one week before starting each of cycle + R-CHOP and group three received famotidine (FAM) 40 mg p.o. once daily one week before cycle and continues daily through the cycle + R-CHOP for six cycles. Blood samples were obtained for biochemical analysis of transforming growth factor-β (TGF-β), Basic fibroblast growth factor (bFGF), interleukin-9 (IL-9), nuclear factor-kappa B (NF-κB) and Caspase 3 before and after six cycles of therapy. The obtained data showed that LAN and FAM resulted in significant decrease in (LDH, TGF-β, bFGF and IL-9, respectively) and significant increase in (Caspase-3). In addition, LAN produced a significant elevation in the response rate compared to the control group or the FAM group. Both LAN and FAM as adjuvant therapy represents a promising anticancer strategy in DLBCL by modulation of malignancy homeostasis mechanisms and boosting chemotherapy antitumor effects without further toxicity. In addition, LAN has a synergetic effect in improving the response rate. Trial registration Clinical Trial.gov Identifier: NCT0364707.

The development of drug resistance remains the major obstacle to clinical efficacy of cancer chemotherapy. Consequently, finding new therapeutic options for cancerous patients is an urgent need. Sixty newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients were recruited from Clinical Oncology Department, Faculty of Medicine, Menoufia University, Egypt prospectively randomized to three groups (n = 20 for each group). Group one (control group) received R-CHOP standard chemotherapy {Rituximab, Cyclophosphamide, Hydroxyldaunorubicin (Doxorubicin)®, Vincristine (oncovin)®, prednisolone in the first five days of cycle}, group two received lansoprazole (LAN) 60 mg p.o. bid for only one week before starting each of cycle + R-CHOP and group three received famotidine (FAM) 40 mg p.o. once daily one week before cycle and continues daily through the cycle + R-CHOP for six cycles. Blood samples were obtained for biochemical analysis of transforming growth factor-β (TGF-β), Basic fibroblast growth factor (bFGF), interleukin-9 (IL-9), nuclear factor-kappa B (NF-κB) and Caspase 3 before and after six cycles of therapy. The obtained data showed that LAN and FAM resulted in significant decrease in (LDH, TGF-β, bFGF and IL-9, respectively) and significant increase in (Caspase-3). In addition, LAN produced a significant elevation in the response rate compared to the control group or the FAM group. Both LAN and FAM as adjuvant therapy represents a promising anticancer strategy in DLBCL by modulation of malignancy homeostasis mechanisms and boosting chemotherapy antitumor effects without further toxicity. In addition, LAN has a synergetic effect in improving the response rate.Trial registration Clinical Trial.gov Identifier: NCT0364707.

Aim This study aimed at evaluating the effect of Nigella sativa (NS) on anthropometric, metabolic and inflammatory parameters and examining its related molecular mechanisms in obese prediabetic individuals as compared to both lifestyle modification (LM) and Metformin (Met). Methods This study included 117 obese prediabetic subjects who were randomized into LM group which followed controlled diet and exercise regimen, metformin group received metformin 500 mg tablets twice daily and NS group received NS oil soft gelatin capsules 450 mg twice daily. Anthropometric (weight, BMI), glycemic, lipid, inflammatory parameters and genetic expressions of Sirtuin-1 (SIRT1) and p53 genes were assessed before and six months after interventions. Results Post-intervention pairwise comparison revealed that, NS was statistically similar to metformin in improving anthropometric, glycemic parameters and SIRT1 gene expression. There was non-significant difference between LM and NS regarding their effects on anthropometric and most of glycemic parameters. Lifestyle modification group showed significantly higher HOMA-B and SIRT1 expression than NS and metformin. Nigella sativa improved lipid panel and significantly reduced TNF-α level and Castelli risk index-I as compared to other interventions. Conclusion Nigella sativa uniquely improved lipid panel and significantly suppressed inflammation. Therefore, Nigella sativa may represent a promising intervention for obese prediabetic subjects. Clinicaltrial.gov ID: NCT03925714 .

Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, has been identified as a critical regulator of bone resorption. Considering the possible role of OPG in rheumatoid arthritis (RA) and in the osteoclastogenesis suppression effects of statins, the present study aims to investigate the effects of fluvastatin on serum levels OPG and disease activity score (DAS) in patients with RA. Forty patients with RA were randomized in a placebo-controlled trial to receive 40 mg fluvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug (DMARD) therapy (methotrexate, leflunomide, hydroxychloroquine). Patients were followed up over 12 weeks. OPG and disease activity variables were measured at baseline and after 12 weeks of treatment. After 12 weeks, the OPG level was significantly increased in the fluvastatin group compared to the placebo group. DAS-28 was significantly decreased in the fluvastatin group compared to the placebo group. C-reactive protein (CRP), morning stiffness, swollen joint count (SJC), and tender joint count (TJC) were significantly decreased in the fluvastatin group compared to the placebo group; however, erythrocyte sedimentation rate (ESR), modified health assessment questionnaire (MHAQ), and visual analogue screen (VAS) were not changed significantly. In conclusion, fluvastatin administration could increase the OPG levels and improve disease activity variables in patients with RA. Therefore, fluvastatin may serve a potential benefit in the treatment of RA patients.

Background & objectives: Rheumatoid artherits (RA) is a refractory disease and the imbalance between pro- and anti-inflammatory cytokines in favor of pro-inflammatory cytokines has been implicated in pathogenesis of RA. In this context, the aim of the present study was to compare the anti-inflammatory and antioxidant effects of candesartan, an angiotensin-receptor blocker, and atorvastatin in RA patients. Methods: In this single-blinded parallel randomized placebo controlled study, the patients recruited between December 2017 and May 2018 were categorized into three groups: group 1 included 15 RA patients who served as control group and received traditional therapy (+ placebo); group 2 included 15 RA patients who received traditional therapy + candesartan (8 mg/day); and group 3 included 15 patients who received traditional therapy + atorvastatin (20 mg/day) for three months. Clinical status in RA patients was evaluated by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI) and morning stiffness before and three months after treatment. All groups were subjected to biochemical analysis of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and malondialdehyde (MDA) before and three months after treatment. Results: Both candesartan and atorvastatin treated groups showed significant decrease in serum levels IL-1β and TNF-α, acute-phase reactants (CRP and ESR), number of swollen joint and patient global assessment. This was also associated with improvement in disease activity and quality of life regarding DAS28 and HAQ-DI as compared to baseline data and the control group. Atorvastatin group showed significant decrease in the serum level of oxidative stress marker (MDA). Interpretation & conclusions: Both candesartan and atorvastatin showed anti-inflammatory effect and immunomodulatory effects leading to improvement in clinical status and disease activity in RA patients. However, atorvastatin was superior to candesartan through its anti-oxidant effect.

Background Infections downregulate cytochrome-P activities and thus may alter drug disposition, especially for drugs with a narrow therapeutic index. Cyclosporine (CyA), still used for the prevention of allograft rejection in renal transplant recipients in Egypt, seems to be affected by these infectious changes, based on random clinical observations. In the present study, the effects of bacterial and fungal infection on CyA metabolism were studied in renal transplant patients and subsequent nephrotoxicity was monitored. Methods Twenty renal transplant patients, diagnosed with fungal or bacterial infection, were recruited from the renal transplantation outpatient clinic in Alexandria University Hospitals. No dose adjustment in CyA was performed at least 1 week before the onset of infection. Exclusion criteria were patients with acute or chronic unstable liver disease, elderly patients, and patients on concomitant drugs affecting CyA metabolism. CyA trough levels and serum creatinine (SCR) concentrations were measured by fluorescence polarization immunoassay and enzymatic assay, respectively, pre-infection, during infection and in many cases, post infection. Results CyA trough levels and SCR concentrations increased significantly during the infection (P

Obesity, insulin resistance (IR), inflammation, and progressive decline in pancreatic β cell function are major features of type 2 diabetes mellitus (T2DM). We aimed to investigate the effect of co-administration of celecoxib (CE) with glimepiride (GL) in the treatment of obese T2DM patients. Body Mass Index (BMI), serum glucose, C-peptide, lipid profile, adiponectin, tumor necrosis factor-α (TNF-α), visfatin, and leptin levels were determined in 40 obese T2DM patients before and after treatment with GL alone or in combination with a selective cyclooxygenase-2 (COX-2) inhibitor CE for 3 months. Homeostasis model assessment of insulin resistance (HOMA2-IR) and atherogenic index (AI) was calculated. Increased levels of serum glucose, C-peptide, total cholesterol (TCH), low-density lipoprotein (LDL-C), triglycerides (TGs), visfatin, TNF-α, leptin, AI, and HOMA2-IR shown in obese diabetic patients were significantly decreased after co-treatment with GL plus CE compared to patients who received GL alone. On the other hand, adiponectin levels showed a significant increase after treatment. The obtained results demonstrate that targeting inflammation using celecoxib with glimepiride improves insulin resistance, glycemia, and inflammatory process in obese type 2 diabetics.

Background: statins are used routinely in patients with coronary artery disease for their lipid lowering effects. Some clinical studies have found that statins do not affect clinical outcomes in patients with chronic heart failure (CHF), while others have found that statins have many beneficial effects. The aim of this study was to evaluate the pleiotropic effects of atorvastatin on patients with chronic heart failure of ischemic etiology (IHF) using conventional echocardiography and tissue doppler imaging. Patient & Methods: Forty­eight patients with (CHF) were divided randomly into two equal groups; Atorvastatin group (received conventional therapy of HF plus atorvastatin 20 mg/d orally) and Original Research Article El-Sisi et al.; BJPR, 6(5): 343-357, 2015; Article no.BJPR.2015.076 344 Control group (received conventional therapy only) for 3 months. Patients were examined both before and after treatment for biochemical tests; serum tumor necrosis factor α (TNF­α), serum high sensetive c reactive protein (hs­CRP), oxidized low density lipoprotein (ox­ LDL), noradrenaline, adrenaline, renin, brain naturetic peptide (BNP­32), Troponin­I, total lipid profile and malondialdehyde. Conventional Echocardiography including left ventricle (LV) dimensions & wall thickness, ejection fraction (EF), E/A ratio, and tissue Doppler imaging (TDI) including Isovolumic contraction (IC), mitral annulus systolic velocity(S­peak), early (E) and late (A) diastolic peak velocities and Tei index were performed. Results: Atorvastatin group showed statistically significant decreased in TNF­ α, hs­CRP, ox­LDL, BNP­32 and noradrenaline compared to their baseline values before the study. Conventional echo failed to detect significant changes in each group except for significant increase in E/A ratio in atorvastatin group. DTI demonstrated that atorvastatin group showed significant improvement in systolic function [significant increase in S wave & isovolumic contraction (IC) peak velocities and better diastolic function [E peak velocity increased & E/E' ratio decreased significantly]. Tei index and heart rate improved significantly in atorvastatin group. Conclusion: Atorvastatin improved cardiac function, decreased inflammatory and oxidative stress parameters as well as modulated the neurohormonal imbalance in CHF patients.

Osteoporosis is the most important metabolic bone disease in patients with diabetes mellitus. Several studies have documented that metformin is osteogenic in vitro. In contrast, others showed no effect of metformin on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Incretin hormones have received much attention because of their beneficial effects beyond glycemia, including on bone health. The study evaluated the anti-osteoporotic effect of metformin and sitagliptin in postmenopausal diabetic women. Forty postmenopausal diabetic women were randomly divided into two equal groups. Group 1 received metformin (Glucophage(®) 500 mg) 1 tablet twice daily, and group 2 received sitagliptin (Januvia(®) 100 mg) 1 tablet/day, for 12 weeks. Fasting blood and urine samples were collected for measurement of serum total alkaline phosphatase (ALP), osteocalcin, and urinary deoxypyridinoline (DPD). Laboratory tests were measured at baseline, after 4 and 8 weeks, and at the end of the study. Bone mineral density of the anterior posterior lumbar spine was measured by dual energy X-ray absorptiometry at baseline and after 12 weeks of the intervention. In the metformin-treated group, the mean values for all markers of bone turnover at 12 weeks of treatment were not significantly different from baseline. In group 2, the mean serum total ALP was significantly decreased, serum osteocalcin levels were non-significantly decreased gradually by 10% at 12 weeks, while urinary DPD decreased significantly and was then maintained at 28% decrease at 12 weeks. In conclusion, metformin is neither osteogenic nor has anti-osteoporotic effect, while sitagliptin could positively regulate bone metabolism.

Aim: To investigate the interaction of slidenafil and green tea in normal healthy male volunteers using probe drugs (midazolam, CYP3A4 activity). Study Design: Ten healthy males were included in random crossover single dose study. Each volunteer received one tablet of sildenafil 50 mg and one tablet of midazolam 7.5 mg concurrently either after drinking 250 ml of water or 250 ml of fresh extract of 2 gram of green tea. After one week washout period, each volunteer received the other intervention. Plasma samples were analyzed for sildenafil and midazolam using HPLC. Place and Duration of Study: The Laboratory of Pharmaceutical Research Center of Faculty of Pharmacy, Tanta University, Egypt, between June to July 2013. Methodology: Blood samples were obtained after the insertion of peripheral cannula into the forearm. Samples were obtained before sildenafil and midazolam intake (blank) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 10, and 12 hours after sildenafil and midazolam administration. The samples were collected in clean heparinized tubes. Plasma was obtained by centrifugation and was stored at –20° until assay. Plasma samples were analyzed for sildenafil and midazolam using HPLC. Results: Coadministration of green tea with sildenafil tea increased the extent but not the rate of sildenafil absorption. It resulted in higher plasma concentrations (AUC∞ increased from 484.2 ± 67.27 μg hr/L to 731.5 ± 111.01 μg hr/L (90% CI 1.50 (1.36-1.66) and the Cmax from 318.9 ± 46.8 μg /L to 414.9 μg/L ± 67.0 μg/L (90% CI 1.29 (1.15-1.43). The elimination rate constant of sildenafil was significantly decreased and the elimination half life was prolonged by about 36%. However, AUC∞ of midazolam increased by 16% and Cmax by 14%; suggesting a small reduction CYP 3A4 activity. Conclusion: Increased bioavailability of sildenafil after green tea intake may be caused by the effect of catechins which can alter spontaneous activity of small intestine or an effect on transporters. Patients who are taking green tea may need smaller doses of sildenafil, and those at higher risk of developing sildenafil adverse effects and are taking green tea should seek medical advice before taking their sildenafil therapy.

Recently, growing multiple uses of silymarin (SIL) as a complementary and alternative medicine, for alcohol-induced liver disease, acute and chronic viral hepatitis, as well as some other nonhepatic indications have been reported. Therefore, more attention should be paid for the hormonal side effects of SIL. Since the available data on the possible estrogenic effects of SIL is rather rare, this study aimed to further elucidate the different estrogenic effects and antiosteoporotic activity of SIL in ovariectomized (OVX) rats. OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE) or SIL. Uterine and body weight were measured in all animals. Biochemical markers of bone formation (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin), endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)) and serum total cholesterol and total lipids were estimated. Formalin fixed femora and uteri specimens were used for histopathological examination. In addition, the binding property of SIL to the two estrogen receptors (ER) subtypes was tested by molecular docking. EE (strong) and SIL (mild) stimulated uterine weight (increased uterus hyperplastic endometrial glands) but EE only prevented body weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted in protection of trabecula thickness, decreased serum levels of ALP and increased serum levels of both calcium and phosphorus. In contrast to EE, SIL did not decrease OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol, total lipids, LH and FSH and increased serum E2. Both EE and SIL increased serum PTH. The docking study revealed a high affinity of SIL towards ERbeta. In conclusion, findings derived in the present study presented an overview of SIL many estrogenic effects in OVX rats. SIL significantly prevents the bone loss in rats induced by OVX with mild proliferative effects in uterus. The observed effects may be due to additive beneficial effect of SIL on bone either due to direct interaction with ERbeta or increasing bone formation parameters including calcium, phosphorus, osteocalcin and PTH.

Aloe vera L. high molecular weight fractions (AHM) containing less than 10ppm of barbaloin and polysaccharide (MW: 1000kDa) with glycoprotein, verectin (MW: 29kDa), were prepared by patented hyper-dry system in combination of freeze–dry technique with microwave and far infrared radiation. AHM produced significant decrease in blood glucose level sustained for 6 weeks of the start of the study. Significant decrease in triglycerides was only observed 4 weeks after treatment and continued thereafter. No deterious effects on kidney and liver functions were apparent. Treatment of diabetic patients with AHM may relief vascular complications probably via activation of immunosystem.

BACKGROUND: Oxidative stress plays an important role in the development of diabetic cardiomyopathy. Alpha-lipoic acid (ALA) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction. AIM: We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular (LV) dysfunction in children and adolescents with asymptomatic type 1 diabetes (T1D). SUBJECTS AND METHODS: Thirty T1D patients (aged 10-14) were randomized to receive insulin treatment (n = 15) or insulin plus alpha-lipoic acid 300 mg twice daily (n = 15) for four months. Age and sex matched healthy controls (n = 15) were also included. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and 2-dimensional longitudinal strain echocardiography (2DS) before and after therapy. Glutathione, malondialdhyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), Fas ligand (Fas-L), matrix metalloproteinase 2 (MMP-2), and troponin-I were determined and correlated to echocardiographic parameters. RESULTS: Diabetic patients had significantly lower levels of glutathione and significantly higher MDA, NO, TNF-alpha, Fas-L, MMP-2, and troponin-I levels than control subjects. The expression of transforming growth factor beta (TGF-beta) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients. Significant correlations of mitral e'/a' ratio and left ventricular global peak systolic strain with glutathione, MDA, NO, TNF-alpha, and Fas-L were observed in diabetic patients. Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA, NO, TNF-alpha, Fas-L, MMP-2, troponin-I levels, and TGF-beta gene expression. Moreover, alpha-lipoic acid significantly increased mitral e'/a' ratio and left ventricular global peak systolic strain in diabetic patients. CONCLUSION: These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.

Background. Activation of PPAR α modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPAR α agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE) plus chlorpromazine (CPZ) in rats. Method. 100 male albino rats (150-200 gm) were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four groups received either ursodeoxycholic acid, fenofibrate, bezafibrate, or gemfibrozil for 7 days; 2 days before EE + CPZ, three other groups received one of the three fibrates after GW6471, a selective PPAR α antagonist in addition to EE + CPZ. The final group received GW6471 alone. Results. The three fibrates showed marked reduction (P0.05) in serum levels of ALP, GGT, ALT, AST, total bile acids, bilirubin, TNF α , and IL-1 β and in hepatic malondialdehyde level as well as a significant increase in bile flow rate (P0.05) in addition to improvements in histopathological parameters compared to diseased group. In groups which received GW6471, these effects were completely abolished with fenofibrate and partially blocked with bezafibrate and gemfibrozil. Conclusion. Short-term administration of fibrates to EE/CPZ-induced intrahepatic cholestatic rats exerted beneficial effects on hepatocellular damage and apoptosis. Fenofibrate anticholestatic effect was solely PPAR α dependent while other mechanisms played part in bezafibrate and gemfibrozil actions.

AIM: To investigate the anti-oxidative and anti-fibrotic effects of aloe vera in patients with liver fibrosis. METHODS: Aloe vera high molecular weight fractions (AHM) were processed by patented hyper-dry system in combination of freeze-dry technique with microwave and far infrared-ray radiation. Fifteen healthy volunteers as the control group and 40 patients were included. The patients were randomly subdivided into two equal groups: the conventional group was treated with placebo (starch), and AHM group was treated with 0.15 gm/d AHM, both for 12 consecutive weeks. The patients were investigated before and after treatment. Serum activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hyaluronic acid (HA), transforming growth factor-β (TGF-β) and matrixmetalloproteinase-2 (MMP-2) were determined. The reduced glutathione (GSH) and malondialdehyde (MDA) levels in liver were assayed and the expression of hepatic α-smooth muscle actin (α-SMA) was identified by immunohistochemistry. RESULTS: At the start of the study, the hematoxylin and eosin staining revealed fibro-proliferated bile ductules, thick fibrous septa and dense inflammatory cellular infiltration in the patients before treatment. The use of AHM for 12 wk significantly ameliorated the fibrosis, inhibited the inflammation, and resulted in minimal infiltration and minimal fibrosis compared to the conventional group. The enzyme activities of the liver (ALT, AST and ALP) were attenuated after treatment in both groups, and the decrease in the AHM group was more significant as compared with the conventional group. Similar to the AST, the MDA levels were significantly higher before treatment, and were attenuated after treatment in both groups. In contrast, the hepatic glutathione content in the patients were decreased significantly in the AHM group compared to the controls. The serum levels of the fibrosis markers (HA, TGF-β and MMP-2) were also reduced significantly after treatment. The expression of α-SMA was modified in patients before and after treatment as compared with the normal controls. In the conventional group, there was only thin and incomplete parenchymal α-SMA positive septum joining the thickened centrilobular veins, while in the AHM group, few α-SMA positive cells were present in sinusoid and lobule after treatment. CONCLUSION: Oral supplementation with AHM could be helpful in alleviating the fibrosis and inflammation of hepatic fibrosis patients.

This study aimed at comparing the effects of atorvastatin and vitamin E on erectile dysfunction in patients initially irresponsive to sildenafil, with investigation into the underlying possible mechanisms. Sixty patients were randomly divided into three groups: the atorvastatin group received 80 mg daily, the vitamin E group received 400 IU daily and the control group received placebo capsules. Patients were examined both before and after 6 weeks of treatment for biochemical tests; Superoxide dismutase (SOD), glutathione peroxidase (GPO), C-reactive protein (CRP), interleukin-6 (IL-6), nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) and for erectile function tests; International index of erectile function (IIEF-5) scores and Rigiscan. Both atorvastatin and vitamin E showed a statistically significant GPO increase (P

Montelukast, a leukotriene receptor antagonist, is used in the treatment of asthma. The objective of the study reported here was to determine whether multiple doses of clarithromycin or fluconazole affect the pharmacokinetics of montelukast.This was a four-phase cross-over study with a washout period of 2 weeks between phases. In phase 1, 12 volunteers received a single oral dose of 10 mg montelukast. In phase 2, the volunteers received a single, oral dose of 1,000 mg clarithromycin once daily for 2 days, followed by, on day 3, a single oral dose of 10 mg montelukast co-administered with clarithromycin. In phase 3, a single oral dose of 50 mg fluconazole was given once daily for 6 days, followed by, on day 7, a single oral dose of 10 mg montelukast co-administered with 50 mg fluconazole. In the last phase (phase 4), a single oral dose of 150 mg fluconazole was given once daily for 6 days, followed by, on day 7, a single oral dose of 10 mg montelukast co-administered with 150 mg fluconazole. The plasma concentration of montelukast was measured by high performance liquid chromatography for 24 h.Following clarithromycin co-administration, the area under the concentration-time curve from zero to infinity ( AUC(0-∞)) of montelukast increased by 144% [90% confidence interval (CI) 2.03-2.86]. The co-administration of a single oral dose of 150 and 50 mg fluconazole decreased the montelukast AUC(0-∞) by 30.7 (90% CI 0.53-0.81) and 38.8% (90% CI 0.57-0.69), respectively.Clarithromycin increased the plasma concentrations of montelukast whereas fluconazole reduced the plasma concentrations of montelukast. The mechanism of the interaction is probably due to interference of the interacting drugs with transporters mediating the uptake of montelukast.

Background: Skin tags (ST) are the most common benign skin lesions. In obesity, production of inflammatory cytokines by visceral adipose tissue (VAT) macrophages increases significantly. This situation creates

To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis (UC), and their effect on inflammatory mediators and nuclear factor (NF)-kappaB activation in these patients.Thirty patients with mild to moderate UC were randomly classified into two groups: sulfasalazine group, who received sulfasalazine 2400 mg/d; and probiotic group, who received sulfasalazine 2400 mg/d with probiotic. The patients were investigated before and after 8 wk of treatment with probiotic (Lactobacillus delbruekii and Lactobacillus fermentum). Colonic activity of myeloperoxidase (MPO) was assayed with UV spectrophotometry, the colonic content of interleukin (IL)-6 was determined by enzyme-linked immunosorbent assay (ELISA), fecal calprotectin was determined by ELISA, and expression of NF-kappaB p65 and tumor necrosis factor (TNF)-alpha proteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction, respectively.At the start of the study, colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining, and an increase in colonic MPO activity, fecal calprotectin, and expression of colonic TNF-alpha and NF-kappaB p65 proteins. The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6, expression of TNF-alpha and NF-kappaB p65, leukocyte recruitment, as demonstrated by a decrease in colonic MPO activity, and the level of fecal calprotectin compared to sulfasalazine group and the control group (P0.05).Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.