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Research Profile - College of Medicine and Health Science - United ...

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Department <strong>of</strong> Pharmacology<br />

subtype selective toxins from mamba snake<br />

(Dendroaspis) venoms. At present the status <strong>of</strong><br />

M1 <strong>and</strong> M4 receptors in health <strong>and</strong> disease<br />

states in humans are being investigated. Our<br />

results show significant decrease <strong>of</strong> M4, but not<br />

<strong>of</strong> M1 receptors in the hippocampus <strong>of</strong><br />

Alzheimer’s patients compared to controls.<br />

Moreover, changes in these receptors in<br />

adrenalectomized animal models which have<br />

been shown to have a selective loss <strong>of</strong><br />

hippocampal neurons. Attempts to isolate <strong>and</strong><br />

characterize M2, M3, <strong>and</strong> M5 selective toxins is<br />

also in progress. Behavioral, biochemical <strong>and</strong><br />

electrophysiological techniques are also used in<br />

underst<strong>and</strong>ing the role <strong>of</strong> other<br />

neurotransmitters in diabetes, epilepsy,<br />

aggressive behavior, aging, <strong>and</strong> degenerative<br />

diseases.<br />

Pr<strong>of</strong>. Georg Petroianu<br />

Clinical toxicology<br />

Therapy <strong>of</strong> acute organophosphate<br />

poisoning<br />

Organophosphorus cholinesterase inhibitors<br />

(organophosphates) are widely used in<br />

agriculture, in industry <strong>and</strong> technology, <strong>and</strong> in<br />

military technology. According to the WHO,<br />

more than one million casualties per year are<br />

due to organophosphates exposure. Countries<br />

<strong>of</strong> the Indian subcontinent <strong>and</strong> adjacent regions<br />

top the list. While use <strong>of</strong> atropine in the therapy<br />

<strong>of</strong> acute organophosphate poisoning is wellestablished<br />

clinical practice, the use <strong>of</strong> oxime<br />

enzyme reactivators (pralidoxime, obidoxime)<br />

is a hotly debated issue. Recent in vivo data<br />

from our laboratory shows that oximes produce<br />

a spurious signal when ChE activity is<br />

determined photometrically. True enzyme<br />

protection/reactivation is thus less than<br />

assumed. Furthermore high dose oxime<br />

increases the “time-to-extubation (TTE)” <strong>and</strong><br />

mortality as compared to identical therapy<br />

without oxime (animal data). The paradigm <strong>of</strong><br />

enzyme reactivation in organophosphate<br />

poisoning must be reassessed <strong>and</strong> alternatives<br />

developed. Screening <strong>of</strong> benzamide<br />

compounds with cholinesterase protective<br />

capabilities is a present priority <strong>of</strong> our group.<br />

Preliminary experiments performed in our<br />

laboratory in vitro <strong>and</strong> in vivo suggest that the<br />

benzamide compound tiapride is partially<br />

protective against esterase inhibition by<br />

organophosphates. In addition newly<br />

synthesized oximes with superior reactivating<br />

properties are tested in conjunction with<br />

benzamides to increase survival in exposed<br />

animals.<br />

Pr<strong>of</strong>. MY Hasan<br />

Neuroscience<br />

The main line <strong>of</strong> research has been focusing on<br />

neurotransmission. We have been applying<br />

behavioral, biochemical <strong>and</strong> electrophysiological<br />

<strong>and</strong> morphological techniques in<br />

underst<strong>and</strong>ing the role <strong>of</strong> neurotransmitters in<br />

various disorders (diabetes, epilepsy, aging,<br />

neurodegenerative diseases). Findings indicated<br />

significant modification <strong>of</strong> specific<br />

neurotransmitters in many <strong>of</strong> the disorders. It<br />

appears that alteration in calcium mobilization<br />

<strong>and</strong> free radical system may be a common factor<br />

accounting for some <strong>of</strong> the changes observed<br />

in aging, diabetes <strong>and</strong> Parkinson's disease.<br />

Another line <strong>of</strong> research has been toxicological<br />

studies <strong>and</strong> impact <strong>of</strong> toxins on muscle the<br />

nervous system. We have investigated the effects<br />

<strong>of</strong> heavy metal intoxication in relation to<br />

FIGURE 1<br />

degenerative diseases. We studied impact <strong>of</strong><br />

heavy metal toxicity on nervous system <strong>and</strong><br />

muscle <strong>and</strong> observed that free radicals may be<br />

involved in metal toxicity <strong>and</strong> antioxidants like<br />

ascorbic acid <strong>and</strong> alpha-tocopherol may have a<br />

protective role against metals effects Also we<br />

have been looking at neurotoxicity <strong>and</strong> general<br />

toxicity from organophosphates <strong>and</strong> nerve<br />

gases. We have been screening antidotes for<br />

organophosphate poisoning <strong>and</strong> implication<br />

for treating exposure to nerve gas agents.<br />

Furthermore my interest covered broad areas in<br />

medical education <strong>and</strong> community health. Some<br />

63

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