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Mohammad Raish Ajaz Ahmad Mushtaq Ahmad Ansari Khalid M. Alkharfy Abdul Ahad Altaf Khan Fahad I. Aljenobi Naushad Ali Abdullah M. Al-Mohizea 《Yao wu shi pin fen xi = Journal of food and drug analysis.》2019,27(1)
Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans. 相似文献
23.
Isabel Tol Elspeth Cumber Daphne Nakakande Silvana Wijaya Catherine Turberfield Abdul Badran Safia Siddiqui Prakhar Srivastava Bethany Chung Molly Dineen Cariosa Devlin Claire Worrall Rebecca Green Emily Bennett Elizabeth Golding Ashling Lillis Ami Sabharwal Andrew S. Protheroe Robert A. Watson 《European journal of cancer care》2020,29(3)
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Inga Koneczny Dorit Rennspiess Florit Marcuse Nathalie Dankerlui Myurgia Abdul Hamid Marina Mané-Damas Jos Maessen Paul Van Schil Abhishek Saxena Paraskevi Zisimopoulou Konstantinos Lazaridis Mark Woodhall Katerina Karagiorgou John Tzartos Socrates Tzartos Marc H. De Baets Peter C. Molenaar Alexander Marx Pilar Martinez-Martinez 《Autoimmunity reviews》2019,18(1):50-55
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen. In early-onset AChR MG (EOMG), the thymus plays an important role in immunopathogenesis, and early thymectomy is beneficial. It is still unknown if the thymus plays any role in Lrp4-MG. In this pilot study, we compared thymus samples from four patients with Lrp4-MG (one pre-treated with immunosuppressive drugs), four non-MG controls and five EOMG patients (not pretreated with immunosuppressive drugs). Immunohistochemistry of the Lrp4-MG thymi revealed normal architecture, with normal numbers and distribution of B-cells, lymphoid follicles and Hassall's corpuscles. Primary CD23+ lymphoid follicles were similarly infrequent in Lrp4-MG and control thymic sections. In none of the control or Lrp4-MG thymi did we find secondary follicles with CD10+ germinal centers. These were evident in 2 of the 5 EOMG thymi, where primary lymphoid follicles were also more frequent on average, thus showing considerable heterogeneity between patients. Even if characteristic pathological thymic changes were not observed in the Lrp4 subgroup, we cannot exclude a role for the thymus in Lrp4-MG pathogenesis, since one Lrp4-MG patient went into clinical remission after thymectomy alone (at one year follow-up) and one more improved after thymectomy in combination with immunosuppressive therapy. 相似文献
26.
Suzanna G.M. Frints Friederike Hennig Roberto Colombo Sebastien Jacquemont Paulien Terhal Holly H. Zimmerman David Hunt Bryce A. Mendelsohn Ulrike Kordaß Richard Webster Margje Sinnema Omar Abdul‐Rahman Vanessa Suckow Alberto Fernndez‐Jan Kees van Roozendaal Servi J.C. Stevens Merryn V.E. Macville Salwan Al‐Nasiry Koen van Gassen Norbert Utzig Suzanne M. Koudijs Lesley McGregor Saskia M. Maas Diana Baralle Abhijit Dixit Peter Wieacker Marcus Lee Arthur S. Lee Elizabeth C. Engle Gunnar Houge Gyri A. Gradek Andrew G.L. Douglas Cheryl Longman Shelagh Joss Danita Velasco Raoul C. Hennekam Hiromi Hirata Vera M. Kalscheuer 《Human mutation》2019,40(12):2270-2285
Pathogenic variants in the X‐linked gene ZC4H2, which encodes a zinc‐finger protein, cause an infrequently described syndromic form of arthrogryposis multiplex congenita (AMC) with central and peripheral nervous system involvement. We present genetic and detailed phenotypic information on 23 newly identified families and simplex cases that include 19 affected females from 18 families and 14 affected males from nine families. Of note, the 15 females with deleterious de novo ZC4H2 variants presented with phenotypes ranging from mild to severe, and their clinical features overlapped with those seen in affected males. By contrast, of the nine carrier females with inherited ZC4H2 missense variants that were deleterious in affected male relatives, four were symptomatic. We also compared clinical phenotypes with previously published cases of both sexes and provide an overview on 48 males and 57 females from 42 families. The spectrum of ZC4H2 defects comprises novel and recurrent mostly inherited missense variants in affected males, and de novo splicing, frameshift, nonsense, and partial ZC4H2 deletions in affected females. Pathogenicity of two newly identified missense variants was further supported by studies in zebrafish. We propose ZC4H2 as a good candidate for early genetic testing of males and females with a clinical suspicion of fetal hypo‐/akinesia and/or (neurogenic) AMC. 相似文献
27.
Suchandan Sikder Georgina Price Md Abdul Alim Anil Gautam Robert Scott Simpson Catherine Margaret Rush 《Autoimmunity》2019,52(2):78-87
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune mediated diseases triggered by group A streptococcal (GAS) infections. Molecular mimicry between GAS M-proteins and host tissue proteins has been proposed as the mechanism that initiates autoreactive immune responses in ARF/RHD. However, the individual role of antibodies and T-cells specific for GAS M-proteins in the pathogenesis of autoimmune carditis remains under-explored. The current study investigated the role of antibodies and T-cells in the development of carditis in the Lewis rat autoimmune valvultis (RAV) model by transferring serum and/or splenic T-cells from rats previously injected with GAS recombinant M5 protein. Here we report that serum antibodies alone and serum plus in vitro expanded rM5-specific T-cells from hyperimmune rats were capable of transferring carditis to naïve syngeneic animals. Moreover, the rats that received combined serum and T-cells developed more severe carditis. Recipient rats developed mitral valvulitis and myocarditis and showed prolongation of P-R intervals in electrocardiography. GAS M5 protein-specific IgG reactivity and T-cell recall response were also demonstrated in recipient rats indicating long-term persistence of antibodies and T-cells following transfer. The results suggest that both anti-GAS M5 antibodies and T-cells have differential propensity to induce autoimmune mediated carditis in syngeneic rats following transfer. The results highlight that antibodies and effector T-cells generated by GAS M protein injection can also independently home into cardiac tissue to cross-react with tissue proteins causing autoimmune mediated immunopathology. 相似文献
28.
Rashid Mohammed H. Stevenson Mark A. Vaughan Jane L. Saeed Muhammad A. Campbell Angus J. D. Beveridge Ian Jabbar Abdul 《Parasitology research》2019,118(3):901-911
Parasitology Research - We conducted a longitudinal survey on 13 alpaca farms in four climatic zones of Australia to understand the epidemiology of gastrointestinal nematodes (GINs) of alpacas. A... 相似文献
29.
Manzar Hasnain Syed Sarim Imam Mohd. Aqil Abdul Ahad Yasmin Sultana 《Journal of pharmaceutical innovation》2018,13(4):341-352
Purpose
The aim of the present study was to formulate and optimize lipid blend-based olmesartan medoxomil (OLM) loaded nanoparticulate scaffolds (NLCs) for enhanced oral bioavailability.Method
The OLM-NLCs were formulated using dependent variables in different concentrations of solid lipid, liquid lipid, surfactant, and co-surfactant by using melt emulsification combined with ultrasonication technique. The formulations were experimentally optimized using a three-factor, three-level statistical design approach. The formulated OLM-NLCs were evaluated for various pharmaceutical quality evaluation parameters and further optimized formulation (OLM-NLCopt) was assessed for release kinetics, thermal behavior, and in vivo absorption assessment.Result
The optimized formulation (OLM-NLCopt) showed particle size (138.7 nm), PDI (0.18), and entrapment efficiency (83.65%). The comparative in vitro release study revealed OLM-NLCopt showed significantly higher (p?<?0.05) drug release compare to OLM-susp. The in vivo study showed the OLM-NLCopt indicated nearly 3-fold improvement in oral bioavailability vis-a-vis OLM-susp in mice model.Conclusion
The results of the release study and pharmacokinetic study suggest the potential of OLM-NLCs for improved oral delivery.30.
Mohamad Hasnan Ahmad Ruhaya Salleh Noor Safiza Mohamad Nor Azli Baharuddin Wan Shakira Rodzlan Hasani Azahadi Omar Ahmad Taufik Jamil Mahenderan Appukutty Wan Abdul Manan Wan Muda Tahir Aris 《BMC women's health》2018,18(1):100