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M Y Hasan

Publications and source records attributed to M Y Hasan.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of two pre-exposure treatment regimens in acute organophosphate (paraoxon) poisoning in rats: tiapride vs. pyridostigmine.

Recently, the FDA approved the medical use of oral pyridostigmine as prophylactic treatment of possible nerve agent exposure: the concept is to block the cholinesterase transitorily using the carbamate (pyridostigmine) in order to deny access to the active site of the enzyme to the irreversible inhibitor (nerve agent) on subsequent exposure. We have shown previously that tiapride is in vitro a weak inhibitor of acetylcholinesterase and that in rats administration of tiapride before the organophosphate paraoxon significantly decreases mortality. The purpose of the present study was to compare tiapride- and pyridostigmine-based pretreatment strategies, either alone or in combination with pralidoxime reactivation, by using a prospective, non-blinded study in a rat model of acute high-dose paraoxon exposure. Groups 1-6 received 1 microMol paraoxon (approximately LD75) groups 2-6 received in addition: G(2)50 microMol tiapride 30 min before paraoxonG(3)50 microMol tiapride 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G41 microMol pyridostigmine 30 min before paraoxon G(5)1 microMol pyridostigmine 30 min before paraoxon and 50 microMol pralidoxime 1 min after paraoxon G(6)50 microMol pralidoxime 1 min after paraoxon. Mortality data were compared using Kaplan-Meier plots and logrank tests. Mortality is statistically significantly influenced by all treatment strategies. Tiapride pretreatment followed by pralidoxime treatment (G3) is aux par with pyridostigmine pretreatment followed by pralidoxime treatment (G5). Tiapride pretreatment only (G2) is inferior to pyridostigmine pretreatment only (G4). The best results are achieved with pyridostigmine pretreatment only or pralidoxime treatment only (G4 and G6).

Acute Disease↗
PubMed2006

HPLC analysis of K-48 concentration in plasma.

K-48 is a new oxime-type compound to be used as an enzyme reactivator in the treatment of exposure to organophosphorous compounds. Plasma concentration of K-48 can be determined using reversed-phase HPLC. Analysis using octyl silica stationary phase and ultraviolet-absorbance detection is fast and simple. K-48 displays a relatively high dose-normalized area under the curve as compared to pralidoxime, which might be beneficial for an antidote. After i.m. administration of 50 mumol K-48, the time course of the concentration can be approximated by a straight line between 15 and 120 min meaning the elimination follows zero-order kinetics.

Animals↗
PubMed2006

High-performance liquid chromatographic determination of the plasma concentration of K-27, a novel oxime-type cholinesterase reactivator.

A simple and reliable HPLC method for the determination of the plasma level of K-27, an oxime type antidote of use in organophosphorus poisoning is presented. Separation was carried out by HPLC using an octyl silica stationary phase and a mobile phase consisting of 93% phosphate buffer (pH 2.6) containing octane sulfate sodium salt, and 7% methanol. Quantitative absorbance was monitored at 286 nm. The calibration curve was linear through the range of 1.25-200 microg/mL, that is well beyond the detected plasma level range of K-27. Limit of quantitation was 5 microg/mL. Intra-day and inter-day precisions of the HPLC determinations gave standard deviations as 0.77 and 2.67%, respectively. Following intramuscular administration of 50 micromol (22.31 mg) K-27 in rats, the maximum of K-27 concentration in plasma was reached at about 15 min giving 186 microg/mL and the t(1/2) was 85 min. K-27 displays initial (from 15 trough 120 min) zero order elimination kinetics. Similar results have been found after intraperitoneal administration.

Animals↗
PubMed2006

Tiapride pre-treatment in acute exposure to paraoxon: comparison of effects of administration at different points-in-time in rats.

INTRODUCTION: Accidental and suicidal exposures to organophosphorus compounds (OPC) are frequent. The inhibition of esterases by OPC leads to an endogenous ACh poisoning. Recently, the FDA approved, based on animal experiments, for military combat medical use oral pyridostigmine (PSTG) for pre-exposure treatment of soman; the concept is to block the cholinesterase reversibly using the carbamate pyridostigmine in order to deny access to the active site of the enzyme to the irreversible inhibitor (OPC) on subsequent exposure. We have shown previously that tiapride (TIA) is in vitro a weak inhibitor of AChE. We also have shown recently that in rats coadministration of TIA with the organophosphate paraoxon significantly decreases mortality without having an impact on red blood cell cholinesterase (RBC-AChE) activity. PURPOSE OF THE STUDY: To establish in a prospective, non-blinded study in a rat model of acute high dose OPC (paraoxon; POX) exposure the ideal point in time for TIA pre-treatment administration and to correlate it with measured TIA plasma levels. MATERIAL AND METHODS: There were six groups of rats in each cycle of the experiment and each group contained six rats. The procedure was repeated twelve times (cycles) (n = 72 for each arm; half male and half female). All substances were applied ip. All groups (1-6) received 1 microMol POX ( approximately LD(75)); groups 1-5 also received 50 microMol TIA at different points in time. Group 1 (G(1)): TIA 120 min before POX Group 2 (G(2)): TIA 90 min before POX, Group 3 (G(3)): TIA 60 min before POX, Group 4 (G(4)): TIA 30 min before POX, Group 5 (G(5)): TIA & POX simultaneously, Group 6 (G(6)): POX only. The animals were monitored for 48 hours and mortality/survival times were recorded at 30 min, 1, 2, 3, 4, 24 and 48 h. AChE activities were determined at 30 min, 24 and 48 h in surviving animals. Statistical analysis was performed on the mortality data, cumulative survival times and enzyme activity data. Mortality data was compared using Kaplan-Meier plots. Cumulative survival times and enzyme activites were compared using the Mann-Whitney rank order test. No Bonferroni correction for multiple comparisons was applied and an alpha < or= 0.05 was considered significant. RESULTS: Mortality is statistically significantly reduced by TIA pre-treatment at all points-in-time. Highest protection is achieved if TIA is given 90 to 0 min before OPC exposure. The reduction in mortality is not correlated to TIA plasma levels (C (max) approximately 120 min post ip-administration). TIA pre-treatment is not affecting AChE activity regardless of the timing of administration. CONCLUSION: The lack of correlation between TIA plasma levels and degree of mortality reduction as well as the lack of protective effect on enzyme activity seem to indicate that the site of action of TIA is not the blood. While our hypothesis that TIA would protect AChE in a pyridostigmine-like manner (via protection of the enzyme) could not be confirmed, the reduction in mortality with TIA pre-treatment is nevertheless of potential interest.

Animals↗
PubMed2006

Monitoring the metabolism of moexipril to moexiprilat using high-performance liquid chromatography-electrospray ionization mass spectrometry.

High-performance liquid chromatography combined with a UV absorbance detector and electrospray ionization mass spectrometer is used for the simultaneous analysis of moexipril and moexiprilat in biological samples. Moexipril and moexiprilat are determined in samples metabolized by rat and human liver microsomal preparations, and also in rat urine. The calibration curve is linear in the ng/mL and microg/mL concentration range of the injected moexipril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Subchronic exposure to high-dose ACE-inhibitor moexipril induces catalase activity in rat liver.

The long-term clinical effects of ACE-inhibitors have similarities with those of both fibrates and glitazones, activators of peroxisome proliferator activator receptor (PPAR) alpha and gamma, respectively. The antioxidant enzyme catalase, a heme protein that degrades hydrogen peroxide, is found at high concentrations in peroxisomes. Catalase activity is one of the recognized surrogate markers indicative of PPAR activation in the rat liver. The purpose of the study was to establish the effect of moexipril on catalase activity and to compare it with the effect of both saline controls and that of the known PPAR agonist clofibrate (positive control). Three groups of seven rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day break. The cycle was repeated eight times. After the final cycle (day 56) the animals were sacrificed and liver tissue collected. The number of catalase positive cells in both moexipril group (95% CI 57-61) and clofibrate group (95% CI 72-80) is higher than in controls (95% CI 3-16) (p < or = 0.01). The number of catalase positive cells in the clofibrate group is higher than in the moexipril group (p < or = 0.01). High-dose subchronic exposure to the ACE-inhibitor moexipril induces catalase activity in the rat liver to an extent comparable to fibrates. We suggest that some of the long-term advantages of ACE inhibitor use - beyond mere BP lowering - might be due to a PPAR mediated effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

alpha-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 alpha-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, alpha-tocopherol, lead plus alpha-tocopherol and saline). Lead (1 mg/kg, i.p.), was administered daily for 2 weeks and alpha-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 alpha-tocopherol reversed twitch tension reduction (4.1+/-0.3 g) and modified lead induced delay in half time of decay. Similarly, alpha-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 alpha-tocopherol showed significantly decreased levels of nicotinic receptors. alpha-Tocopherol appears to protect against lead induced neuromuscular dysfunction. These effects of alpha-tocopherol are possibly mediated via a free radical mechanism or modification of calcium homeostasis.

Animals↗
PubMed2004

Trace metal profiles in hair samples from children in urban and rural regions of the United Arab Emirates.

Pollution has increased with industrialization and humans are subjected to exposure to heavy metals from different environmental sources. In oil-producing countries heavy metals are considered a major threat to the population. Metals such as lead, aluminum, manganese, nickel and cadmium may impact various organs of the body, and controlling their toxicity is crucial for individuals at risk. Previous studies utilized blood levels for monitoring metal toxicity. The current study was designed to investigate exposure to lead, aluminum, manganese, nickel and cadmium using scalp hair. Hair samples were randomly collected from 42 children (aged 6-18 y) representing rural and urban areas of the United Arab Emirates. The rural regions were defined as at least 50 km away from factories or traffic sites. Immediately after cutting, hairs were stored in plastic bags and attached to a questionnaire with the relevant background information. Samples were dried, weighed and sealed with polyethylene envelopes. Following extraction procedures with nitric acid, ICP-MS was utilized for metals determination. The analytical instrument showed a high degree of sensitivity and revealed significant differences between levels of some metals in hairs from rural and urban areas. Children from rural areas had mean hair lead levels (microg/g) of 0.79 + 0.10 whereas children from urban area had higher hair lead levels (3.47 + 0.47). Measuring metals concentration in scalp hair could be a useful method for studying exposure and assessing environmental pollution. Although the technique has the potential of being an effective tool for evaluating extent of pollution and identifying potentially toxic elements, it cannot yet replace the standard procedures of measuring air, water and soil metal content.

Adolescent↗
PubMed2003

Effects of ascorbic acid on lead induced alterations of synaptic transmission and contractile features in murine dorsiflexor muscle.

Lead is a common environmental toxin that affects neuromuscular junction and potentially might cause muscle weakness. Antioxidants like ascorbic acid may protect against lead induced myopathy. The present study measured isometric twitch tensions (evoked either directly by muscle stimulation or indirectly by nerve stimulation) to study effects of ascorbic acid on lead induced alterations at murine dorsiflexor skeletal muscle. Resting membrane potentials (RMPs), endplate potentials (EPPs) and miniature endplate potentials (MEPPs) were also recorded. Forty animals were divided into four groups of n = 10 each. (10 control, 10 lead alone, 10 ascorbic acid alone, 10 lead treated plus ascorbic acid). Lead (1 mg/kg) i.p, was administered daily for 2 weeks before the recording day and ascorbic acid (200 mg/kg, i.p) was given daily for 3 weeks prior to the experiment day. Lead treatment reduced twitch tension significantly (from 4.3 +/- 0.5 g to 2.7 +/- 0.2 g) and delayed half time of decay compared to the control. Similarly MEPPs frequencies were reduced following lead treatment. Application of ascorbic acid prevented twitch tension reduction in lead treated mice (3.3 +/- 0.3 g) and reversed lead induced delay in half time of decay. The negative actions of lead treatment on MEPPs frequencies were also modified with ascorbic acid. It appears that ascorbic acid exerts a protective role against lead induced peripheral nerve and muscle dysfunction. This effect of ascorbic acid on lead induced neuromyopathy is probably mediated via a free radical scavenging mechanism or modification of Ca(2+) homeostasis.

Animals↗
PubMed2003

Factors influencing the quality of life of infertile women in United Arab Emirates.

OBJECTIVES: To measure the quality of life in a representative sample of infertile women and evaluate their sociocultural attitude to this condition. METHODS: Two hundred sixty-nine infertile women attending the Assisted Reproduction clinic, Tawam Hospital were consecutively selected. They were interviewed about the effect of infertility on their quality of life using a structured, measurement-specific and pre-tested questionnaire. RESULTS: Parameters mostly affected were mood-related mainly in women above 30 years, with primary and female factor infertility and those in polygamous marriages. Quality of life did not affect sexual performance and was not affected by duration of infertility or cost of treatment. CONCLUSION: The results highlight the importance of bearing children and the stresses exerted on infertile women in Eastern societies. Thorough counseling and continuing support of infertile women is therefore indicated to improve their quality of life.

Adolescent↗
PubMed2003

PD-136,450: a CCK2 (gastrin) receptor antagonist with antisecretory, anxiolytic and antiulcer activity.

This study investigated the effects of PD-136,450 (PD), a highly selective ligand for the CCK2 receptor, on gastric acid and pancreatic secretions, gastric cytoprotection and anxious behaviour in the rat and rabbit. PD inhibited gastrin (but not dimaprit) stimulated acid secretion in anaesthetized and conscious rats (IC50 of 1 mg kg(-1) sc) and inhibited 14C-aminopyrine uptake in isolated gastric glands from rabbits. In addition, PD decreased dose-dependently gastric haemorrhagic lesions in rats treated orally with acidified ethanol. Both, the antisecretory effects on gastric acid secretion and the gastric cytoprotective effects were less potent compared with the proton pump inhibitor omeprazole. PD strongly increased pancreatic secretion, which was substantially inhibited by the CCK1 antagonist L-364,718 (but not by the CCK2 antagonist L-365,260). PD also showed significant anxiolytic activity as assessed by a black and white box two-compartment activity assay. Both, time spent in the dark compartment and latency for movement from the light to the dark compartment was increased by PD (similarly with 5 mg kg(-1) diazepam). In conclusion, PD inhibited gastrin-stimulated gastric acid secretion, decreased ethanol-induced damage to the gastric mucosa, stimulated pancreatic secretion (via CCK1 receptors) and displayed anxiolytic activity. Thus, PD may have utility as an adjunct therapy in peptic ulcer disease by countering the actions of gastrin and increasing acid neutralization and mucosal protection.

Animals↗
PubMed2003

Effects of alpha-tocopherol on diabetes-induced alterations of synaptic transmission and contractile features in murine dorsiflexor muscle.

Diabetes mellitus affects skeletal muscle and free radicals may be implicated in the manifestation of diabetes complications. The present study investigated effects of alpha-tocopherol on diabetic dorsiflexor muscle via recording resting membrane potentials (RMPs), endplate potentials (EPPs), miniature endplate potentials (MEPPs) and isometric twitch tensions. Forty mice were divided randomly into two groups (n = 20). One group served as control and the other was injected once with streptozotocin (STZ) solution (60 mg/kg, i.p) to induce diabetes. The animals were then divided further into two subgroups (n = 10). Alpha-tocopherol (100 mg/kg, i.p) was administered daily to one control and one diabetic group for 3 weeks prior to recording day. Experiments were conducted 4 weeks following diabetes induction. Isometric twitch tension was measured in anaesthetized mice (2 mg/g urethane, i.p) via a transducer connected to a computer system. Resting membrane potentials and MEPPs were measured by utilizing the intracellular recording method. Compared to control, diabetic mice showed reduced twitch tension (4.4 +/- 0.4 g control vs. 2.5 +/- 0.3 g diabetic) and demonstrated delayed half time of decay. Diabetic flexor muscle also displayed significant reduction in MEPPs frequencies with no changes in RMPs. Alpha-tocopherol reversed tension reduction in diabetic mice (from 2.5 +/- 0.3 to 3.8 +/- 0.4 g), impacted delayed half time of decay and reversed reduction in MEPPs frequencies. Alpha-tocopherol exerts a protective role against diabetes-induced peripheral muscle dysfunction. This effect is probably mediated via a free radical scavenging mechanism or modification of Ca2+ homeostasis.

Animals↗
PubMed2002

Student perceptions of tutor skills in problem-based learning tutorials.

OBJECTIVE: The problem-based learning (PBL) tutor plays a role that is different from the role of a teacher in a conventional teaching format. In the Faculty of Medicine and Health Sciences, United Arab Emirates, all students are Arab nationals and tutors are expatriates with different sociocultural backgrounds from the students. This study was designed to investigate how students evaluate tutors in PBL tutorials and whether student evaluations of tutors change with the progress of students in PBL tutorials. METHODS: Differences in tutor performance evaluation by male and female students were also analysed. The students evaluated 12 tutor skills in a scale of 1-3, 1 being 'below average' and 3, 'outstanding'. Student responses from a total of 314 (98.1%) completed forms collected over 2 academic years were analysed statistically. A total of 14 tutors participated in the PBL programme. RESULTS: The analysis revealed that tutors as a group were rated as having average to outstanding tutor skills in 10 items of the evaluation form. Students and faculty perceptions were different for the tutor skills of guiding students for information management. The students expected more support from tutors, whereas the tutors tried to emphasize self-learning in the PBL curriculum. Lower scores to the tutors in the 'problem' bringing sociocultural and religious issues for discussion showed that a gap in sociocultural/religious understanding between students and tutors might influence tutor skills. CONCLUSIONS: Differences in tutor evaluation by male and female students indicate necessity of adopting different strategies by tutors in a different sociocultural background. The results of the study have direct implications for faculty development.

Attitude↗
PubMed2001

Reduced potassium currents in old rat CA1 hippocampal neurons.

Potassium currents are an important factor in repolarizing the membrane potential and determining the level of neuronal excitability. We compared potassium currents in CA1 hippocampal neurons dissociated from young (2-3 months old) and old (26-30 months old) Sprague-Dawley rats. Whole-cell patch-clamp techniques were used to measure the delayed rectifier (sustained) and the A-type (transient) potassium currents. The delayed rectifier current was smaller in old (548 +/- 57 pA) than in young (1193 +/- 171 pA) neurons. In the absence of extracellular calcium, the delayed rectifier current was also smaller in old (427 +/- 41 pA) than in young (946 +/- 144 pA) neurons. The cell membrane capacitance was unchanged in old (13.3 +/- 1.2 pF) compared to young (13.6 +/- 1.2 pF). Therefore, the reduction in the delayed rectifier current was not due to a change in membrane surface area. Moreover, activation and inactivation of the delayed rectifier current were unchanged in old compared to young neurons. The slope of the current-voltage relation, however, was smaller in old (B = 5.03) than in young (B = 9.62) neurons. Similarly, the A-current was smaller in old (100 +/- 16 pA) than in young (210 +/- 44 pA) neurons in the presence of extracellular calcium. This reduction of potassium currents could account for the prolongation of action potentials reported previously for old rat CA1 hippocampal neurons. The age-related reduction in potassium current indicates plasticity in neuronal function that can impact communication in the hippocampal neural network during aging.

Aging↗
PubMed2000

Water deprivation reveals early neuromyopathy in diabetic mice.

The effects of water deprivation on peripheral nerve and muscle function were investigated in flexor digitorum superficialis muscle of control and diabetic mice. Twenty mice (30 g average body weight) were injected once with streptozotocin solution (200 mg/kg) to induce experimental diabetes and another 20 mice of similar body weight served as controls. Two weeks later, comparative analyses of in situ muscle isometric contractile characteristics were performed by direct muscle stimulation and indirect nerve stimulation (at 1, 5 and 30 Hz) in urethane-anesthetized (2 mg/g, i.p.) control and diabetic mice. One day prior to the experiments, 10 control and 10 diabetic mice were deprived of water. The study contained four groups: hydrated (H) control, dehydrated (DH) control, H diabetic and DH diabetic. There were no significant differences in synaptic delay or twitch tension between H control and DH control. Comparing H control and H diabetic groups, no differences were noticed in synaptic delay or twitch tension; except at 30 Hz where twitch tension was reduced in H diabetic mice. Significant differences were observed when comparing DH control and DH diabetic mice. DH diabetic showed a significant increase in synaptic delay (from 7.4 to 9.3 ms) and a significant decrease in twitch tension evoked either by indirect nerve or by direct muscle stimulation (from 4.4 g to 1.9 g and from 4.4 g to 2.3 g, respectively). These results revealed that water deprivation enhances diabetes effects at the neuromuscular junction and at the muscle leading to further complication of neuromyopathy.

Animals↗
PubMed2000

Early morphological remodeling of neuromuscular junction in a murine model of diabetes.

Although skeletal muscle weakness is documented in diabetes, the time course for its development is not established. The present study examined the dorsiflexor muscle from animals that had been diabetic for 2 wk. Adult male c57BL mice were injected once with streptozotocin (STZ) to induce diabetes (60 mg/kg ip). Two weeks later, resting membrane potential and miniature end-plate potentials were recorded, and electron microscopy was utilized for ultrastructural evaluations. After STZ-induced diabetes, both resting membrane potential and miniature end-plate potentials were reduced. Nerve terminals showed less synaptic vesicles and had degenerated mitochondria. Furthermore, in the intramuscular nerves, disorganization of microtubules and neurofilaments was evidenced. Myelin-like figures were present in intramuscular nerves, neuromuscular junctions, and muscle fibers. At the muscle level, mitochondria were swollen, with disorganization of their cristae, disruption of T tubules, and myofibers with more deposition of glycogen granules. The present results revealed early STZ-induced nerve and muscle alterations. Observed ultrastructural modifications resemble those of motoneuron disorders and aging processes. These changes are possibly related to alterations in Ca(2+) mobilization across muscle membrane. Other mechanisms such as free radical-mediated actions may also be implicated in STZ-induced effects on skeletal muscle.

Animals↗
PubMed2000

Cadmium modulates diabetes-induced alterations in murine neuromuscular junction.

Skeletal muscle function is compromised in diabetes mellitus and exposure to heavy metals may further complicate neuromuscular impairments. The present study investigated the effects of cadmium on diabetes induced dorsiflexor muscle dysfunction in C57 BL adult male mice. Forty mice were divided randomly into 2 groups (n=20 each). One group served as control and the other was injected once with i.p. streptozotocin (STZ) solution (60 mg/kg) to induce experimental diabetes. Each group was then divided into two sub-groups (n=10) of which one received 5 mM cadmium. Utilizing intracellular recording method, resting membrane potential (RMP) and miniature endplate potentials (MEPPs) were measured in dorsiflexor muscle obtained from urethane-anaesthetized (2 mg/g, i.p.) four weeks diabetic and matched control mice. Comparative analyses of isometric contractile characteristics of in situ dorsiflexor muscle were also conducted in both groups. In control mice, flexor muscle exposure to 5 mM cadmium for 10 min resulted in significant reduction in MEPPs frequencies and isometric twitch tensions without affecting RMP. In STZ-diabetic mice, the same exposure did not modify resting membrane potential and further decreased MEPPs frequencies and isometric twitch tensions. Current results indicated that cadmium probably via a Ca2+ antagonist and chelating activity at nerve terminals exacerbates diabetes complications.

Animals↗