Mohammed Y. Hasan

Cellular and molecular actions of Methylene Blue in the nervous system.

Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide‐induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimers disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system.

Assessing patient satisfaction with community pharmacy in the UAE using a newly-validated tool

BACKGROUND Patient satisfaction has become an integral component of the quality of healthcare services. It has been used for the purpose of performance assessment, reimbursement, and quality management of health service delivery. It has been suggested that patient satisfaction could be a predictor of health-related behavior. OBJECTIVES To develop and validate a tool for use within the Arabic context to assess patient satisfaction. To assess patient satisfaction with current community pharmacy services in the UAE using the validated tool. METHODS A systematic process was used to develop an assessment tool that could be used within the Arabic context and establish its validity and reliability. Survey participants assessed their satisfaction with the services based on a 5-point Likert-type scale: Poor = 1, Fair = 2, Good = 3, Very good = 4, Excellent = 5. The anonymous questionnaire was distributed over a 5-month period to eligible participants in public places such as malls and shopping markets, in various emirates across the UAE. Those who were 21 years or older, taking at least one scheduled (regular) medication and having adequate Arabic or English language proficiency were included. RESULTS The instrument comprised four dimensions: Information, Relationship, Accessibility and Availability. Participants required more information about medications and self-management (Mean = 2.49 ± 1.19). Measures of competence, i.e., care, interest, time, confidence and trust, could also be improved (Mean = 3.05 ± 1.07). Accessibility scores measuring physical, geographical and financial items were lowest (Mean = 2.80 ± 1.33). Overall scores on availability of medications indicated relative satisfaction with this dimension (Mean = 3.51 ± 0.7). CONCLUSIONS This study is the first to use a patient satisfaction tool specifically developed for the Arabic context. Patient satisfaction scores in all dimensions were significantly lower than published data, suggesting patients have unmet expectations of community pharmacy services in the UAE. Stakeholders could utilize this information to help in the design and delivery of improved services that could lead to increased demand.

Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium

The cholinergic nervous system has been demonstrated to attenuate the inflammatory response during sepsis via the inhibitory action of acetylcholine (ACh) on macrophages. These findings were largely based on experimental sepsis models using endotoxin as the inducing agent. Herein, however, we report that the specific inhibition of acetylcholinesterase (AChE) renders animals more resistant to infection by a virulent strain of Salmonella enterica serovar Typhimurium, a Gram‐negative enteric pathogen. Inhibition of AChE was induced by a subchronic exposure to paraoxon, a potent anti‐cholinesterase metabolite of the organophosphorous compound parathion. Our findings indicate that inhibition of AChE enhanced survival of infected mice in a dose‐dependent fashion and this correlated with efficient control of bacterial proliferation in target organs. Immunologically, inhibition of AChE enabled the animals to mount a more effective inflammatory anti‐microbial response, and to secrete higher levels of interleukin‐12, a key T helper type 1‐promoting cytokine. The ACh‐induced enhancement in resistance to infection was abrogated by co‐administration of an oxime which can reactivate AChE. Hence, in a model of Gram‐negative bacterial infection, cholinergic stimulation is shown to enhance the anti‐microbial immune response leading to effective control of bacterial proliferation and enhanced animal survival.

Alpha Tocopherol Protects Against Immunosuppressive and Immunotoxic Effects of Lead

Chronic exposure to lead (Pb) is associated with multi-organ toxicity. The precise mechanism(s) involved, however, remains incompletely defined. The present study was undertaken to analyze the effect of Pb on the immune system and determine the ability of f tocopherol (AT) to reverse Pb-induced immunotoxicity. Groups of TO Mice (6 per group) were treated ip for 2 weeks with saline alone, Pb acetate alone, Pb plus AT, or with AT alone. Spleens were then analyzed for (i) cellular composition by flow cytometry, (ii) cellular response to B and T cell mitogens and (iii) production of nitric oxide (NO). Pb treatment resulted in a significant state of splenomegaly associated mainly with an influx of CD11b + myeloid cells. Surprisingly, however, these cells exhibited no upregulation in expression of activation markers and did not produce NO. The lymphocyte mitogenic responses were inhibited by S 70% in Pb-treated group. Concurrent treatment with Pb and AT resulted in almost a complete reversal of Pb-induced splenic cellular influx. Despite this, however, mitogenic responses in Pb+AT treated group were approximately 50% of those observed in normal (saline-treated) controls. We conclude that (1) chronic treatment with Pb acetate induces a state of splenomegaly and decreased proliferation in response to mitogenic stimuli and (2) co-treatment with AT largely reversed the cellular influx but this was associated with only a partial improvement of the mitogenic responses. These results highlight the role of AT as a potentially effective antioxidant in the immune system.

Protective Drugs in Acute Large-Dose Exposure to Organophosphates: A Comparison of Metoclopramide and Tiapride with Pralidoxime in Rats

Weak and reversible inhibitors of cholinesterase(s), when coadministered in excess with a more potent inhibitor such as organophosphates, can act in a protective manner. The benzamide compound, metoclopramide, confers some protection (putatively via this mechanism) for cholinesterases against inhibition by paraoxon both in vitro and in vivo, after chronic small-dose exposure. Tiapride is a related benzamide. In this study, we compared the protection by metoclopramide and tiapride in rats acutely exposed to large doses of paraoxon with the therapeutic “gold standard,” pralidoxime. Group 1 received 1 &mgr;mol paraoxon (approximately 75% lethal dose), Group 2 received 50 &mgr;mol metoclopramide, Group 3 received 50 &mgr;mol tiapride, Group 4 received 50 &mgr;mol pralidoxime, Group 5 received 1 &mgr;mol paraoxon + 50 &mgr;mol metoclopramide, Group 6 1 &mgr;mol paraoxon + 50 &mgr;mol tiapride, and Group 7 1 &mgr;mol paraoxon + 50 &mgr;mol pralidoxime. All substances were administered intraperitoneally. The animals were monitored for 48 h and mortality was recorded at 30 min, 1, 2, 3, 4, 24, and 48 h. Blood was taken for red blood cell acetylcholinesterase measurements at baseline, 30 min, 24, and 48 h. With the exception of Group 7, in which some late mortality was observed, mortality occurred mainly in the first 30 min after paraoxon administration with minimal changes occurring thereafter. Mortality at 30 min was 0% in the metoclopramide, tiapride, and pralidoxime groups and 73 ± 20 (paraoxon), 65 ± 15 (paraoxon + metoclopramide), 38 ± 14 (paraoxon + tiapride), and 13 ± 19 (paraoxon + pralidoxime). Mortality at 48 h was 75 ± 18 (paraoxon), 67 ± 17 (paraoxon + metoclopramide), 42 ± 16 (paraoxon + tiapride), and 27 ± 24 (paraoxon + pralidoxime). Metoclopramide does not significantly influence mortality after acute large-dose paraoxon exposure. Both tiapride and pralidoxime significantly decreased mortality in our model. The protection conferred by tiapride was significantly less than that conferred by pralidoxime at 30 min, but was not significantly different at 24 and 48 h.

Lipophilicity Determination of Some ACE Inhibitors by TLC

Abstract A simple and reliable reversed-phase TLC method was used to determine the lipophilicity of ACE inhibitors. The TLC silica plates were saturated with paraffin using continuous development with 10% paraffin in hexane for 18 hours. The TLC silica particles covered with the paraffin are used as an inexpensive substituent of the usual RP-18 TLC stationary phase.

α-Tocopherol Modifies Lead Induced Functional Changes at Murine Neuromuscular Junction

Lead impacts neuromuscular junction and might induce skeletal muscle weakness. Antioxidants may prevent toxic actions of lead on muscle. In this study, resting membrane potentials, endplate potentials, miniature endplate potentials (MEPPs) and isometric twitch tensions were recorded to investigate effects of α-tocopherol (Vitamin E) on lead induced changes at murine dorsiflexor muscle. Moreover, levels of endplate nicotinic receptors were measured by receptor autoradiography. Forty rats were divided into four groups (lead alone, α-tocopherol, lead plus α-tocopherol and saline). Lead (1 mg/kg, i.p.), was administered daily for 2 weeks and α-tocopherol (100 mg/kg, i.p.) was given daily for 3 weeks. Lead treatment significantly reduced twitch tension (from 4.4±0.4 to 2.2±0.3 g) and delayed half time of decay. MEPP frequencies and quantal content were also significantly reduced after lead treatment. Pretreatment with α-tocopherol reversed twitch tension reduction (4.1±0.3 g) and modified lead induced delay in half time of decay. Similarly, α-tocopherol modified the negative actions of lead exposure on MEPP frequencies and quantal content. Receptor autoradiographic studies revealed significant increase of nicotinic receptor levels at the endplate region of flexor muscle in lead treated mice. However, animals treated with lead plus α-tocopherol showed significantly decreased levels of nicotinic receptors. α-Tocopherol appears to protect against lead induced neuromuscular dysfunction. These effects of α-tocopherol are possibly mediated via a free radical mechanism or modification of calcium homeostasis.