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Biomedical subjects

M Tariq

Publications and source records attributed to M Tariq.

At least 19 recordsLinked to original sources

Baclofen attenuates harmaline induced tremors in rats.

Recent experimental and clinical studies clearly suggest the role of gamma-aminobutyric acid (GABA) in the pathogenesis of tremors. The present study was undertaken to investigate the effect of baclofen, a GABA B receptor agonist on harmaline induced tremors. Four groups of female Wistar rats weighing 100+/-15 g were injected with harmaline (10 mg/kg, intraperitoneally) for inducing experimental tremors. The animals in groups 2, 3 and 4 were given baclofen by gavage at doses of 2.5, 5 and 10 mg/kg, respectively, half an hour before harmaline administration, whereas, the rats in group 1 served as control and received water. The latency of onset, intensity and duration of tremor and electromyographic (EMG) responses were recorded. Treatment with baclofen resulted in a dose dependent decrease in the intensity of tremor. Our EMG study also revealed a significant decrease in the amplitude of tremors in baclofen treated rats. A highly significant increase in latency of onset of tremor was observed in the rats treated with high dose (10 mg/kg) of baclofen only. This study clearly suggests beneficial effects of baclofen in harmaline induced tremors.

Animals↗

Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP models of Parkinsonism in rodents.

Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in the development of experimental parkinsonism. In this investigation an attempt was made to determine a possible protective effect of quinacrine (QNC), a PLA2 inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30 mg/kg, i.p.) daily for 5 days. QNC was injected i.p. in the doses of 0, 10, 30 and 60 mg/kg daily 30 min before MPTP in four different groups. Two other groups of mice received either vehicle (control) or a high dose of QNC (60 mg/kg). Two hours after the last injection of MPTP, striata were collected for the analysis of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and glutathione (GSH). For the 6-OHDA study, male Wistar rats were infused with 6-OHDA (60 microg) in the right striatum under chloral hydrate anesthesia. The rats in different groups were treated with 0, 5, 15 and 30 mg/kg QNC (i.p.) for 4 days, while first injection was given 30 min before 6-OHDA. On day 5, rats were sacrificed and striata were stored at -80 degrees C. Administration of MPTP or 6-OHDA significantly reduced striatal DA, which was significantly attenuated by QNC. Concomitant treatment with QNC also protected animals against MPTP or 6-OHDA-induced depletion of striatal GSH. Our findings clearly suggest the role of PLA2 in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further studies are warranted to explore the therapeutic potential of PLA2 inhibitors for the treatment of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.

The gene products involved in mammalian mitochondrial DNA (mtDNA) maintenance and organization remain largely unknown. We report here a novel mitochondrial protein, Twinkle, with structural similarity to phage T7 gene 4 primase/helicase and other hexameric ring helicases. Twinkle colocalizes with mtDNA in mitochondrial nucleoids. Screening of the gene encoding Twinkle in individuals with autosomal dominant progressive external ophthalmoplegia (adPEO), associated with multiple mtDNA deletions, identified 11 different coding-region mutations co-segregating with the disorder in 12 adPEO pedigrees of various ethnic origins. The mutations cluster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity.

Amino Acid Sequence↗

The effects of magnesium sulphate and EDTA in the hypercholesterolaemic rabbit.

Numerous clinical reports suggest the beneficial effects of chelation therapy for the treatment of atherosclerosis. However, the results of these studies are inconclusive and controversial. The purpose of this present study was to examine the prophylactic and therapeutic effects of chelation liquid (CHL) in experimental atherosclerosis. Twenty New Zealand white rabbits were fed a 1% cholesterol-supplemented diet for 45 days. In the prophylactic phase of the study subcutaneous 300 mg EDTA + 500 mg magnesium sulphate (MgSO4) injections (five rabbits) and isotonic saline (five rabbits) were given to test and control groups, respectively, along with cholesterol rich diet. The CHL treatment ameliorated the rise of serum cholesterol and serum triglyceride concentrations, lowered serum calcium concentrations and reduced the aortic atheroma. In the therapeutic phase of the experiment the cholesterol diet was stopped and the remaining 10 animals were returned to normal diet. Five of these rabbits were given CHL injections and other five animals were given isotonic saline injections for 121 days. Although the level of cholesterol and triglyceride were not significantly different in the two groups, the serum calcium concentration and the percentage of the area of flate aortic specimen occupied by atheroma were significantly lower in the CHL treated rabbits as compared to controls. It is concluded that CHL injections have a definite prophylactic effect on atherogenesis in the cholesterol-fed rabbit, and may have some therapeutic value in the regression phase. Further confirmatory studies are suggested.

Animals↗

MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity.

P-glycoprotein (PGP), the product of the multidrug resistance gene (MDR1), acts as an energy-dependent efflux pump that exports its substrates out of the cell. PGP expression is an important factor regulating absorption of a wide variety of medications. It has also been associated with intrinsic and acquired cross resistance to a number of structurally unrelated anticancer drugs. A single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T, was recently correlated with PGP protein levels and substrate uptake. Individuals homozygous for the T allele have more than four-fold lower PGP expression compared with CC individuals. As overexpression of PGP has been associated with altered drug absorption, therapy-resistant malignancies, and lower concentrations of HIV-1 protease inhibitors, this SNP may provide a useful approach to individualize therapy. To facilitate clinical application throughout the world, 1280 subjects from 10 different ethnic groups were evaluated for this SNP using the polymerase chain reaction-restriction fragment length polymorphism assay and the genotype and allele frequency for each group were ascertained. Marked differences in genotype and allele frequency were apparent between the African populations and the Caucasian/Asian populations (P < 0.0001). The Ghanaian, Kenyan, African American and Sudanese populations studied had frequencies of 83%, 83%, 84% and 73%, respectively, for the C allele. The British Caucasian, Portuguese, South-west Asian, Chinese, Filipino and Saudi populations had lower frequencies of the C allele compared to the African group (48%, 43%, 34%, 53%, 59%, and 55%, respectively). The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Interethnic variability in human drug responses.

The scientific study of interethnic differences in responses to drugs has been extant for 80 years. Many of these differences have been described at the phenotypic level, and some have been explained by genetic factors. However, it is frequently difficult to disentangle accurately the hereditary and environmental influences in phenotypic comparisons. This is where the recent developments in knowledge of the genes responsible for drug receptors are starting to make a big impact. The beta 2 adrenoceptor is described; it has three genetic polymorphisms. The different genotypes influence responses to agonists such as albuterol (Salbutamol). New gene frequency data including those for Saudi Arabians, Indians, and Africans are shown. The expanding body of knowledge about genetic (and interethnic) variability in drug receptors is likely to be important in clinical medicine.

Ethnicity↗

Vitamin E decreases valproic acid induced neural tube defects in mice.

The present study was undertaken to investigate the effect of vitamin E on valproic acid (VPA) induced teratogenesis. Pregnant Balb mice were divided into six groups of 10-11 animals each. The mice in group 1 served as control and were injected with saline subcutaneously on day 8 of gestation, whereas, animals in group 2 received a single injection of VPA (700 mg/kg (s.c.)). Groups 3 and 4 received an oral administration of vitamin E in the doses of 250 and 500 mg/kg, respectively, 1 h before VPA injection. Group 5 and 6 were given vitamin E only, in the same doses as group 3 and 4. On day 18 of gestation, the mice were killed by cervical dislocation. Embryotoxicity was assessed by counting the number of implants, live and dead fetuses, resorptions, crown rump length and fetal body weight. The fetuses were observed for malformations including neural tube defects (excencephaly), open eye lid and micrognathae. VPA administration resulted in a significant reduction of the average live fetuses/litter, fetal weight and crown rump length and a significant increase in malformations (excencephaly, open eye lid and micrognathae). Concomitant administration of vitamin E significantly attenuated VPA induced decrease in the fetal weight, crown rump length and malformations.

Administration, Oral↗

Effect of lidocaine on harmaline-induced tremors in the rat.

The present study was undertaken to investigate the effect of lidocaine on harmaline-induced tremors in the rat. Four groups of Wistar rats weighing 45-50 g were injected with harmaline (50 mg/kg i.p.) for inducing experimental tremors. The rats in group 1 served as control, whereas the animals in groups 2, 3, and 4 were also given lidocaine i.p. at doses of 12.5, 25, and 50 mg/kg, respectively, 10 min after the onset of tremors (therapeutic study). In a separate four groups of animals intraperitoneal lidocaine injection was given 10 min before harmaline (prophylactic study) in the same dose regimen as mentioned above. The latency of onset, intensity, and duration of tremor and electromyographic responses were recorded. Lidocaine dose dependently attenuated harmaline-induced tremors in rats. The latency period was increased, and duration and intensity of harmaline-induced tremors was reduced by lidocaine. Our electromyography (EMG) study also revealed a decrease in the amplitude of harmaline-induced tremors in lidocaine-treated rats. In conclusion, the results of this study clearly suggest beneficial effects of lidocaine in harmaline-induced tremors.

Animals↗

Effect of pentaglobin and piperacillin on survival in a rat model of faecal peritonitis: importance of intervention timings.

BACKGROUND: Faecal peritonitis is a progressive pathophysiological condition which may lead to multiple organ failure and death. The reason for the associated morbidity and mortality could be attributed to the fact that some of the subtle alterations in cellular function that occur during the early stage of peritonitis are unidentified and consequently missed, leading to inadequate or delayed intervention. Recent studies have shown that early treatment with antibiotic and antisera containing antibodies to lipopolysaccharide (immunoglobulin) improve the survival rate in these patients. The present investigation was undertaken to study the effect of pentaglobin and piperacillin with particular attention to time lag of drug intervention on animal survival following experimental peritonitis. METHODS: Experimental peritonitis was produced by inoculating 1 ml/kg of faecal suspension (2:1 w/v in saline) into the peritoneal cavity. Two groups of animals were treated with pentaglobin (4 ml/kg) or piperacillin (1000 mg/kg) respectively, whereas rats in another group received both drugs simultaneously. The first dose of each drug was given at 4 h, 6 h, 8 h and 12 h after faecal inoculation followed by 3 additional doses at 8-h intervals. For biochemical studies, separate groups of animals were used in which the treatment was started 4 h after faecal inoculation and the animals were killed at 12 h after the treatment. RESULTS: Both piperacillin and pentaglobin prolonged survival time of animals which received the treatment within 6 h of faecal insult. The combination of pentaglobin plus piperacillin produced better results as compared to the individual effect. There was a significant decrease in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase in catalase following faeces-induced septicaemia, suggesting a significant increase in oxidative stress. The changes in enzyme levels were significantly attenuated by both the drugs. CONCLUSION: The findings suggest that intervention with a combination of pentaglobin and antibiotics within 6 h of peritonitis might significantly improve survival rate in rat.

Animals↗

Effect of lithium on cyclosporin induced nephrotoxicity in rats.

Psychoactive drugs provide essential intervention in the care of transplant recipients, yet little is known of their interaction with immunosuppressants such as cyclosporin (CSA). Lithium (Li) is an invaluable drug for the treatment of manic disorders in organ transplant patients. As both these drugs are known to produce renal toxicity, the concomitant use of CSA and Li may be potentially harmful. The present study was undertaken to investigate the effect of CSA and Li chloride individually and in combination on renal structure and function of rats. Male Sprague-Dawley rats were divided into the following eight groups of seven animals each: group I, control (vehicle only); group 2, Li (2 mEq/ kg i.p.) alone; group 3, CSA 12.5 mg/kg (subcutaneous); group 4, CSA 25 mg/kg; group 5, CSA 50 mg/kg; group 6, CSA 12.5 mg/kg + Li; group 7, CSA 25 mg/kg + Li; and group 8, CSA 50 mg/kg + Li. The drugs were given once a day for seven days; Li being administered 30 min before CSA. Twenty four hours after the last dose of drugs the animals were sacrificed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Li levels. The left kidney was analyzed for malondialdehyde (MDA) and conjugated dienes (CD) levels and right kidney was used for histopathological studies. Our results showed that Li alone did not produce any significant renal toxicity, whereas CSA dose dependently caused structural and functional changes in kidneys. However, significantly higher structural and functional impairment was observed in the animals treated with Li plus CSA as compared to CSA alone treated animals. Several fold increase in blood Li level was also noticed in the rats concomitantly treated with CSA and Li. A significant increase in MDA and CD in the rats treated with CSA plus Li suggests the role of oxidative stress in drug induced nephrotoxicity. These findings clearly demonstrate that even non toxic doses of Li may significantly exacerbate CSA induced nephrotoxicity in rats. The enhanced nephrotoxicity following concomitant use of these drugs may be attributed to significant increase in the bioavailability of Li and enhanced oxidative stress. Further clinical studies are warranted to investigate the interaction of these nephrotoxic drugs in human subjects.

Animals↗

Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a pathologic, cytogenetic, and molecular study of a case with a novel translocation t(9;17)(q22;q11.2).

A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was histochemical, immunohistochemical, and ultrastructural evidence of neuroendocrine differentiation is reported. Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.

Biomarkers, Tumor↗

Foreign bodies in the nasal cavities: a comprehensive review of the aetiology, diagnostic pointers, and therapeutic measures.

Otolaryngologists frequently encounter nasal foreign bodies, particularly among children and mentally retarded patients. There are isolated reports describing the removal of unusual foreign bodies from the nose. But no comprehensive reviews of this important subject have been published for many years. This article includes a detailed discussion of the different types of nasal foreign bodies, the various clinical presentations, management options, and complications associated with nasal foreign bodies.

Adolescent↗

Lipoma in fossa of Rosenmüller.

We report the first case of a lipoma originating in the fossa of Rosenmüller. Although lipomas are a common benign tumour in the body, lipomas of the nasopharynx are rare.

Adult↗

Penetrating neck injury: case report and evaluation of management.

Greater urban violence has resulted in an increased incidence of penetrating neck trauma. Penetrating neck wounds can present difficult diagnostic and therapeutic dilemmas. The evaluation and management of such injuries, however, remains controversial. There is no universally accepted specific approach to the management of patients with penetrating neck injuries, with some surgeons advocating mandatory neck exploration whilst others believe in selective surgical intervention. We believe that an equal willingness for both conservative and surgical intervention as dictated by serial bedside evaluation with adequate radiological and endoscopic support can provide the clinician a safe and effective means of managing a potentially complex and lethal problem.

Adult↗

Pleomorphic adenoma of the retropharyngeal space: a rare location.

A case of an isolated pleomorphic adenoma of the retropharyngeal space is reported, this has not been documented previously in the literature. Attention is drawn to the wide spectrum of benign and malignant neoplasms that can potentially occur within this complex anatomical region. The importance of a systematic and logical approach to the management of such lesions is emphasized.

Adenoma, Pleomorphic↗

Effect of aluminum on neurological recovery in rats following spinal cord injury.

OBJECT: This investigation was undertaken to study the effect of aluminum on neurobehavioral, electrophysiological, structural, and biochemical changes in rats following spinal cord injury (SCI). METHODS: Adult male Sprague-Dawley rats classified into different groups were given aluminum sulfate-dosed drinking water in the concentrations of 0%, 0.25%, 0.5% and 1%, respectively. After 30 days of aluminum treatment, the animals were subjected to spinal cord trauma. Laminectomy was performed at T7-8 in anesthetized rats, followed by placement of a compression plate (2.2 x 5 mm) loaded with a 35-g weight over the exposed spinal cord for 5 minutes. Control animals underwent the same surgical procedure, but the compression injury was not induced (sham). Postoperative neurological function was assessed using the inclined-plane test and by obtaining a modified Tarlov score and vocal/sensory score daily for 10 days. Electrophysiological changes were assessed using corticomotor evoked potentials, whereas pathological changes were assessed by light microscopy. The level of vitamin E in the spinal cord was measured as an index of antioxidant defense. The behavioral, biochemical, and histological analyses were performed in a blinded fashion. CONCLUSIONS: Analysis of results obtained in the behavioral studies revealed that the compression of spinal cord produced transient paraparesis in which a maximum motor deficit occurred at Day 1 following SCI and resolved over a period of 10 days. Administration of aluminum significantly impaired the recovery following SCI. Analysis of the results of the biochemical, electrophysiological, and histopathological studies also confirmed the deleterious effects of aluminum on recovery from SCI in rats.

Aluminum↗

Identification of a novel fusion gene involving hTAFII68 and CHN from a t(9;17)(q22;q11.2) translocation in an extraskeletal myxoid chondrosarcoma.

A proportion of extraskeletal myxoid chondrosarcomas (EMC) have been shown to have a characteristic translocation t(9;22)(q22;q12) involving the EWS gene at 22q12 and the CHN orphan nuclear receptor gene at 9q22. This translocation appears to be largely specific for EMC, but has not been detected in all such tumours. We report here a case of EMC with a t(9;17)(q22;q11.2) as the sole chromosome abnormality. We have determined that the translocation results in the fusion of the entire coding region of CHN to the N-terminal transactivation domain of RBP56/hTAFII68. This is the first report of a translocation involving RBP56/hTAFII 68, a protein with sequence homology to both EWS and TLS/FUS. The involvement of RBP56/hTAFII68 may explain some unusual features of the tumour.

Amino Acid Sequence↗