Drug Research

BACKGROUND: This study aimed to evaluate the effectiveness of metformin and pioglitazone in combination with vitamin E on sonography grade and liver enzymes level in patients with non-alcoholic fatty liver disease. METHODS: A randomized controlled clinical trial was designed with 68 patients diagnosed with non-alcoholic fatty liver disease by sonography and clinical examinations. Sixty-eight patients were randomly divided into two groups; 34 were assigned to receive 15 mg of pioglitazone per day and 34 were assigned to receive 1000 mg of metformin per day for 6 months...

BACKGROUND: Mesenchymal stem cells (MSCs) modulate immune responses, and their immunomodulatory potential can be enhanced using inflammatory cytokines. Here, the modulatory effects of IFN-γ-licensed MSCs on expression of T cell-related chemokines and chemokine receptors were evaluated using an experimental autoimmune encephalomyelitis (EAE) model. MATERIAL AND METHODS: EAE was induced in 3 groups of C57bl/6 mice and then treated with PBS, MSCs and IFN-γ-treated MSCs...

Skin provides an excellent barrier to molecular transport, as the stratum corneum is the most formidable barrier to the passage of most pharmaceuticals. Various attempts have been made to improve drug administration into the body through intact skin. Though very few routes are as attractive as the topical route, drug transport through the skin is challenging. To overcome the challenges, researchers have found a system in which the drug is encapsulated into the vesicle, penetrating deeper into the skin to hit the target site...

BACKGROUND: Inhalation preparation involves liquid or solid raw materials for delivering to lungs as aerosol or vapor. The liquid preparation for nebulizer is effective for convenient use and patient compliance and it has been extensively used in the treatment of clinical lung diseases. Clinical staff often mixes the compound ipratropium bromide with beclomethasone propionate and budesonide inhaler but reference values of inhalants for clinical use need to be established for simplifying the operation procedure...

Imatinib mesylate (IM) is the gold standard for treatment of Chronic Myeloid Leukemia (CML). This study aimed to gain more knowledge of the altered PK, pharmacogenetic factors, and gene expression leading to variable IM levels. Fifty patients with chronic phase-CML were enrolled in this study and divided as 25 responders and 25 non-responders (patients are directly recruited after response assessment). HPLC/MS/MS was used to determine trough and peak concentration of imatinib and N-desmethyl imatinib in the blood...

Oximes, as classical acetylcholinesterase (AChE) reactivators, have some pharmacokinetics/pharmacodynamics disadvantages. During the synthesis of non-oxime compounds, we encountered the compound 2-formylbenzoic acid (2-FBA) with promising in vitro and in vivo cholinesterase (ChE) reactivating properties in the acute exposure to diazinon (DZN). For in vitro experiments, the healthy mice serum and brain homogenate were freshly prepared and exposed to DZN (160 µg/mL). After 10 minutes, 2-FBA was added to the poisoned samples, and ChE activity was measured afterward...

INTRODUCTION: This paper sought to scrutinize the role of microRNA-32 (miR-32) on the growth and migration as well as on the expression of metastatic genes in PC3 cells of prostate cancer in vitro. METHODS: Subsequent transfection of cells with miR-32 mimics, miR-32 inhibitor, negative control (NC), cell proliferation using MTT, and apoptosis by ELISA were performed. Furthermore, qRT-PCR was directed to measure the expression levels of matrix metalloproteinase 2 (MMP2) and vascular endothelial growth factors (VEGF) as metastatic and angiogenesis genes in the progression of PC3...

Malaria is one of the world's most devastating diseases, infecting well over 300 million people annually and killing between 2 and 3 million worldwide. Increasing parasite resistance to many existing drugs is exacerbating disease. Resistance to commonly used malarial drugs is increasing the need to develop new drugs urgently. Due to the slow pace and substantial costs of new drug development, repurposing of old drugs which is recently increasingly becoming an attractive proposition of highly efficient and effective way of drug discovery led us to study the drug rifampicin for this purpose...

BACKGROUND: Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI...

BACKGROUND: There are studies that suggest that some benzamide derivatives may exert effects on heart failure; however, their molecular mechanism is not very clear. OBJECTIVE: The aim of this research was to evaluate the biological activity of a 4-hydroxy-furanyl-benzamide derivative against heart failure translated as area infarct. METHODS: Biological activity produced by 4-hydroxy-furanyl-benzamide derivative against heart failure was determinate using an ischemia-reperfusion injury model...

BACKGROUND: There are reports which indicate that some cyclooctyne derivatives may exert changes in cardiovascular system; however, its molecular mechanism is not very clear. OBJECTIVE: The aim of this study was to evaluate the biological activity of four cyclooctyne derivatives (compounds 1: to 4: ) produced on infarct area and left ventricular pressure. METHODS: Biological activity produced by cyclooctyne derivatives on infarct area was determinate using an ischemia/reperfusion injury model...

BACKGROUND: This study aimed to evaluate the potential neuroprotective effect of cyclosporine - a calcineurin inhibitor-, ondansetron, and tropisetron-5-hydroxytryptamine (serotonin) 3 receptor (5-HT3R) antagonists-, on optic nerve crush (ONC) injury in rats. Moreover, underlying signaling activities of their beneficial neuroprotective effects were studied. METHODS: Adult male rats were treated with the intravitreal administration of cyclosporine (1.6 mM), ondansetron (100 nM), and tropisetron (100 nM) immediately after the induction of ONC...

Curcumin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory and tissue protective. In here we hypothesized that curcumin-loaded chitosan-coated solid lipid nanoparticles (CuCsSLN) are able to increase its overall bioavailability and hence its antioxidant and mitochondria;/lysosomal protective properties of curcumin. CuCsSLN were prepared using solvent diffusion technique for formation of solid lipid nanoparticles (SLNs) and electrostatic coating of positive-charged chitosan to negative surface of SLNs...

Mitochondrial dysfunction is a basic mechanism leading to drug nephrotoxicity. Replacement of defective mitochondria with freshly isolated mitochondria is potentially a comprehensive tool to inhibit cytotoxicity induced by ifosfamide on renal proximal tubular cells (RPTCs). We hypothesize that the direct exposure of freshly isolated mitochondria into RPTCs affected by ifosfamide might restore mitochondrial function and reduce cytotoxicity. So, the aim of this study was to assess the protective effect of freshly isolated mitochondrial transplantation against ifosfamide-induced cytotoxicity in RPTCs...

Therapeutic drug monitoring investigations based on saliva samples can be utilized as an alternative to blood sampling for many advantages. Moreover, the development of physiologically based pharmacokinetic (PBPK) modeling tools can further help to estimate drug exposure from saliva. This review discusses the use of saliva samples and illustrates the applications and examples of PBPK modeling systems for estimating drug exposure from saliva.

BACKGROUND: Chronic pain represents a significant and costly healthcare problem especially in the older patient. Transdermal opioid therapy is easy to apply and ensures constant supply of active ingredients. However, skin irritation, poor adhesion and systemic side effects complicate transdermal pain therapy. METHODS: In the Relief study, comprising 54 centers, all in Germany, 252 patients were recruited and data about the general care situation as well as the characteristics, effects and side effects of the Aloe vera fentanyl patch were collected...

BACKGROUND: Aging is tightly linked to chronic disease, frailty, and death. Multi-morbidity, defined as the presence in the same patient of three or more conditions such as neoplastic, cardiovascular, neurodegenerative, metabolic, or autoimmune diseases, becomes more common with age. METHODS: The study was performed in a double-blind fashion. Subjects within each dose cohort (Cohorts 1, 2, 3, and 4) were randomly assigned to receive Isomyosamine doses (between 150 mg to 600 mg or placebo) or placebo in a 3:1 ratio (6 active: 2 placebo)...

Studies have shown the ability of benzodiazepine drugs to cause memory loss in animals and humans. Midazolam is a benzodiazepine commonly administered intravenously during surgical procedures because it reacts rapidly, causes anterograde amnesia, and has few side effects. It has also been used in palliative medicine where, among others, an oral route has been employed for chronic administration of the drug. The current study evaluated the effects of chronic orally administered midazolam on spatial working memory and procedural memory in control and experimental female rats over a three-week experimental period utilizing the Morris water maze...

A series of 7 compounds with isoxazole - indole - γ-resorcylic acid scaffold, segregated into B2 & A2 series, wherein, B2 comprises Compounds: 13, 14, 15 & 16 and A2 comprises Compounds: 10, 11 & 12, on the basis of the variable substituents at the indole, resorcinol and isoxazole end of the scaffold as in Figure: 1, were designed and docked with human estrogen receptor: 1ERRα. The Binding affinity (BA) and the interacting amino acids compared with reference selective estrogen receptor modulators (SERM's) such as Raloxifene, Estradiol, Bazedoxifene, Bisphenol, Genistein, Daidzein, Ormiloxifene, Tamoxifen, 6-hydroxy-naphthalen-2yl-benzo(D)-isoxazol-6-ol(1) using PyRx software and their ADME properties predicted with SWISS ADME online tool...

BACKGROUND: Pulmonary hypertension (PH) is a pathophysiological disorder, which involves multiple clinical conditions such as the upregulation of the Rho/ROCK signaling pathway. On the other hand, fasudil as a Rho kinase inhibitor has been investigated in the treatment of PH in some clinical studies. OBJECTIVES: The present systematic review and meta-analysis aimed to evaluate the human clinical trials regarding the efficacy of fasudil in the management of PH. METHODS: Databases were searched with pre-defined search terms, up to December 2021...