Ciliotherapy: A Novel Intervention in Polycystic Kidney Disease

Background Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as ‘cilio-therapy’. Methods and Results In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopa- minergic agonist to regulate cilia length and function

Protective Effect of Ginger Extract Against Cisplatin-Induced Hepatotoxicity and Cardiotoxicity in Rats.

The protective effect of ginger extract against cisplatin-induced hepatotoxicity and cardiotoxicity was evaluated in 30 albino white rats(weighing 200-300 gm ) classified into 5groups (6 rats per each group). The rats were treated with 0.5g/kg/day or         1g/kg/day ginger extract orally 5 successive days before and 5 successive days after induction of toxicity with intraperitoneal (IP) injection of (10mg/kg ) cisplatin, resulted in a significant reduction in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) , total serum  billirubin(TSB) , lactate dehydrogenase (LDH) and creatine kinase(CK) enzymes in comparison with the cisplatin treated animals; ginger extract also improves the histological changes produced by cisplatin in the liver cells and cardiac muscle fiber cells  in comparison with the control .  It is  concluded that , ginger extract when used concomitantly with cisplatin protects the liver and heart against the toxicity induced by this cytotoxic drug.                                         Key wards :Ginger, Cisplatin,Oxidative Stress

The Protective Effect of Honey Against Amikacin- induced Nephrotoxicity in Rats

Drug –induced nephrotoxicity is an important cause of renal failure. Aminoglycoside antibiotics, such as amikacin, which causes ototoxicity and nephrtotoxicity as a main side effects, this is focused on the use of natural materials as antioxidants against the toxic oxidative action that exert a cell damaging effect. The most important one of these materials is the honey. The aim of this work is to evaluate the antioxidant effects of honey against amikacin – induced nephrotoxicity.18 albino rats divided into 3 groups (6 rats per each group), group 1 received I.P daily dose of normal saline (control), group 2 received (35  mg/kg/day) I.P dose of amikacin ,and group 3 received (35mg/kg/day) of amikacin I.P dose in combination with oral dose of honey(500mg/kg/day) for 2 weeks. All animals (at 15th day) were anesthetized by ether and sacrificed; blood samples were collected for the subsequent measurement of the serum creatinine, urea, malneldehyde (MDA) and glutathione (GSH) while an isolated kidney was kept in 10 % of formaldehyde for the histopathological examination. This study showed that amikacin causes nephrotoxicity represented by elevation of serum level of creatinine and urea, MDA and a decrease in the serum glutathione level. While the administration of honey in combination with amikacin reduced the nephro-toxic effect of amikacin that represented by a reduction of the serum creatinine and urea, MDA and elevation of glutathione levels with improvement of the kidney histological findings in comparison with group 2.This study concluded that, honey decreased nephrotoxicity induced by amikacin through interference with the oxidative stress process, i.e. honey acts as free radical scavenger. Key words:amikacin, honey, nephrotoxicity, oxidative stress

Melatonin Potentiates the Therapeutic Effects of Metformin in Women with Metabolic Syndrome

Objective: This study evaluated the effect of melatonin on the response of patients suffering from metabolic syndrome (MEBS) treated with metformin. Design: This study used two-armed groups in a double-blind, randomized controlled clinical trial. Materials and Methods: A randomized double-blind placebo-controlled study was carried out on female patients diagnosed as having MEBS, according to the International Diabetes Federation (IDF) diagnosing criteria of MEBS (2005), from the outpatient clinic in Al-Zahraa Teaching Hospital/Kut, Iraq. They were diagnosed utilizing laboratory and clinical investigations, then randomized into two groups. The first group (group A) was treated with metformin (500 mg) twice daily, in addition to a placebo formula once daily at bedtime for three months. The second group (group B) was treated with metformin (500 mg) twice daily after meals, in addition to melatonin (10 mg) once daily at bedtime for three months. Results: The treatment of patients with MEBS using metformin–melatonin showed an improvement in most MEBS components such as fasting serum glucose (FSG), lipid profile, and body mass index (BMI), in addition to a reduction in insulin resistance and hyperinsulinemia. Simultaneously, there were increments in serum uric acid (UA), leptin, prolactin (PRL), and estradiol levels, while serum progesterone level decreased. Furthermore, patients treated with metformin–placebo showed less improvement in the studied parameters compared to that produced due to the inclusion of melatonin in the treatment protocol. Conclusion: Melatonin improves the effect of metformin on several components of MEBS such as FSG, lipid profile, and BMI, in addition to insulin resistance and hyperinsulinemia, compared to metformin alone

The RNA polymerase "switch region" is a target for inhibitors

The alpha-pyrone antibiotic myxopyronin (Myx) inhibits bacterial RNA polymerase (RNAP). Here, through a combination of genetic, biochemical, and structural approaches, we show that Myx interacts with the RNAP "switch region"--the hinge that mediates opening and closing of the RNAP active center cleft--to prevent interaction of RNAP with promoter DNA. We define the contacts between Myx and RNAP and the effects of Myx on RNAP conformation and propose that Myx functions by interfering with opening of the RNAP active-center cleft during transcription initiation. We further show that the structurally related alpha-pyrone antibiotic corallopyronin (Cor) and the structurally unrelated macrocyclic-lactone antibiotic ripostatin (Rip) function analogously to Myx. The RNAP switch region is distant from targets of previously characterized RNAP inhibitors, and, correspondingly, Myx, Cor, and Rip do not exhibit crossresistance with previously characterized RNAP inhibitors. The RNAP switch region is an attractive target for identification of new broad-spectrum antibacterial therapeutic agents.status: publishe