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Home > Pharmacological Screening of Nsaid’S for Their Probable Central Nervous System Effect and Their Role in Neurodegenerative Diseases

Pharmacological Screening of Nsaid’S for Their Probable Central Nervous System Effect and Their Role in Neurodegenerative Diseases

Thesis Info

Access Option

External Link

Author

Naeem, Sadaf.

Program

PhD

Institute

University of Karachi

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2015

Thesis Completion Status

Completed

Subject

Pharmacognosy

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/9471/1/Sadaf%20Naeem_Pharmacolgy_2015_UoK.doc

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726880821

Similar


Inducible cyclo-oxygenase (COX) expression in the brain is associated with acute neurotoxicity, such as seizures and ischemia. On the other hand COX 1 and 2 both are related to delayed pro-inflammatory activities, which are ought to exacerbate the neuronal damage in neurodegenerative diseases. It was postulated in last decade that non steroidal anti-inflammatory drugs (NSAIDs) which are widely used in clinical situation as anti-inflammatory, analgesics and antipyretic drugs by inhibiting COX pathway in brain can prevent neurodegeneration. However it is still unknown whether NSAIDs have effect on the development on the central nervous system and play a major role to prevent and treat neurodegenerative disease. Previous clinical, epidemiological and experimental data revealed that repeated and long term use of NSAIDs prevent neurodegeneration by inhibiting brain COX isoenzymes and recommended as a new emerging approach. In the present study we aimed to evaluate the effect of diclofenac, ibuprofen and celecoxib on behavioral and biochemical parameters as well as disease severity assessment not only in parkinson’s patients but on chlorpromazine induced parkinson rat model. A single blind clinical study was conducted in four groups of 40 parkinson’s patients. The cognition was measured by MMSE and MoCA test, depression assessed by HDRS test, daily living functioning judged with ADCS-ADL scale and disease severity by Hoehn & Yahr staging and descriptive UPDRS scale. The outcomes were better among patients treated with NSAIDs than control patients. NSAIDs treated patients showed significant improvement in MMSE, MoCA and ADCS-ADL scores after 2 month treatment period from baseline score. However insignificant results were also observed after 2 month treatment with respect to depression and disease severity. The most frequent adverse events during 2 month treatment period were nausea, dyspepsia, elevated hepatic enzymes, and hypertension. NSAIDs showed significant increased SGOT, SGPT, and bilirubin levels but no significant change in GGT and alkaline phosphatase after 2 month treatment was noted. NSAIDs showed significant increased levels of urea and creatinin after 2 month. We found elevated Cortisol levels at baseline in all parkinson patients after taking NSAID we observed slightly reduced levels of cortisol from baseline as compare to control patients but results were insignificant. Behavioral and histopathological examination of NSAIDs treated rats after chlorpromazine induced parkinsonism was observed. NSAIDs were administered after 30 minutes of 3mg/kg ip injection of chlorpromazine up to 21 day. After 21 day we observed significant motor impairment in CPZ treated rat in open field, catalepsy and wire hanging test while NSAIDs treated rat showed significant improvement comparable to standard L-dopa/carbidopa group. NSAIDs treated rats showed significant improved cognitive behaviors in radial arm maze, water maze and passive avoidance test as compare to control and CPZ group. Depression was marked with CPZ group on forced swimming induced test and cage crossing test while NSAIDs treatment improved depression after 21 days. NSAIDs treated rats slightly reduced their weight after 21 days as compare to control and CPZ group while CPZ group significantly increased body weight. Anxiety was assessed by using elevated plus maze. NSAIDs showed anxiety like behavior after 21 day treatment but CPZ treated rats showed anxiolytic effect. Histopathological examination of brain tissue of NSAIDs treated group revealed minimal neuronal destruction and gliosis as compare to CPZ group. In conclusion results of this clinical and experimental study explain that NSAIDs treatment show moderate improvement in parkinson associated cognitive decline, motor impairment and in their daily life function. Adverse drug events were also observed, hence prolong use can only be recommended after extensive study.
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کامیابی

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ڈھل جانی اے یار جوانی اے
تیری ڈولی جنگل جانی اے
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اوہ پینڈا دور دراز دا اے
اوتھے پہلا پچھ نماز دا اے
اوہ جانوں راز نیاز دا اے
کر عمل تے کھٹ بہار کُڑے
کر نال ملاّح دے پیار کُڑے
تدھ چوڑا چھن چھن چھنکے نی
گل پا حضوری منکے نی
رنگ دار تے ونکو ونکے نی
توں ہس کے وقت گزار کُڑے
کر نال ملاّح دے پیار کُڑے

تیرے وال سنہری بھاندے نیں
جو ویکھن خوشیاں پاندے نیں
ایہہ ہسن چار دناں دے نیں
نہیں لگنا فیر بزار کڑے
کر نال ملاّح دے پیار کُڑے

تینوں سائیں سنہڑے گھلے نی
توں خرچہ بنھ لے پلے نی
جاندی نوں کہڑا ٹھلے نی
توں کیتا سی اقرار کُڑے
کر نال ملاّح دے پیار کُڑے

قادریؔ دی گل پلے پاویں
اکھیں کسے دے نال نہ لاویں
سچے در تے سیس نواویں
تینوں ملسی چین قرار کُڑے
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غیر مسلموں سے تعلقات اور بقائے باہمی کی اساس: سیرت النبیﷺ کے تناظر میں

Islam is universal Religion which not only clear with issues related to Muslims but also clarify the rules and regulations to have intinary with Non-Muslims. Islam emphasizes on primary/ basic rules about relationship of Muslims and Non- Muslims Communities; justice, peace, mutual harmony and co-operation. No force conversion and freedom of thought, Non compulsion Of impartiality convenant. Islam forces on mutual existence in according of these rules. So, clash of civilizations can be avoided in the present age.

Epidemiology, Haematology and Thyerapy of Large Strongyles Infestation in Thoroughbred Horses

Our study consists of three parts. Part -1 deals with epidemiological study in which one year field survey of 2400 thoroughbred horses at Sahiwal, Lahore, Sargodha and Mandi Baha-ud-Din districts were surveyed revealing the prevalence of strongylosis as 40.83 %, 38.17 %, 43.33 %, and 39.83 % respectively. This study has drawn a compelling evidence that the disease is prevalent thoroughout Punjab province with remarkable overall prevalence of 40.54 %. We further explored that hot and humid environment favours its prevalence, age and sex of the horses has no effect on the prevalence and it is maximum in summer while lowest in winter. This study also demonstrates 79.58 % prevalence of internal parasitism among thoroughbred horses overall at Punjab province. Part -2 deals with study of haematology, serum enzymes and electrolytes on 30 thoroughbred horses suffering from large strongyles infection and treated with piperazine adipate. This study revealed a higly significant (p >0.05) decrease in RBC, Hb, Neutrophil percentage, Na, K and Mg in diseased horses. The decrease in RBCs and haemoglobin exhibited normocytic normochromic anaemia. There was a significant decrease in monocyte percentage in diseased animals. A highly significant (p >0.05) increase in eosinophils, SGPT, SGOT, LDH, and a significant increse in basophils percentage was recorded in diseased horses. No significant increase / decrease (p <0.05) was noted in the levels of TLC, lymphocyte percentage, CPK and Ca in diseased horses. Part 3 deals with therapeutic trials of allopathic and herbal drugs. This study was conducted on 110 thoroughbred horses suffering from large strongyles infestation. Present study revealed that aqueous extract of N. sativa seeds at the dose rates of 50, 100 and 150 mg/kg body weight is highly effective and showed 87.50 %, 87.82 % and 88.35 % efficacy 28 days post treatment respectively. Aqueous extracts of F.parviflora arial parts at the dose rates of 50, 100 and 150 mg/kg body weight showed 62.74 %, 80.68 % and 81.74 % efficacy 28 days post treatment respectively. Aqueous extracts of Fl. macrophylla arial parts at the dose rates of 50, 100 and 150 mg/kg body weight exhibited 66.92 %, 73.38 % and 74.04 % efficacy 28 days post treatment respectively whereas 100 % efficacy rate of piperzine adipate (allopathic drug) at the dose rate of 110 mg/kg body was noted. Among the herbal drugs efficacy was found maximum in N.sativa followed by F.parviflora whereas the lowest with Fl. macrophylla.