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Biomedical subjects

N Agrawal

Publications and source records attributed to N Agrawal.

At least 37 records · Page 2Linked to original sources
PubMed1999

The occurrence of toothwear in users of Ecstasy (3,4-methylenedioxymethamphetamine).

UNLABELLED: Ecstasy users have reported that dry mouth, jaw tension and tooth grinding were common side effects of its use although the influence of these effects upon toothwear have not been previously investigated. OBJECTIVE: This study aimed to compare incisal and occlusal toothwear in Ecstasy users and a group of non-users of Ecstasy but users of other drugs. METHODS: Groups were established by a snowball peer information network from visitors to the "drop-in" Maryland Centre in Liverpool. Volunteers completed a questionnaire about social life, drug use and diet. Clinical examination for wear on the incisal edges and on canine tips was conducted with a mirror and probe, whereas occlusal wear was recorded in impressions and subsequently scored from stone replica casts. The degree of toothwear was scored according to the criteria of the Tooth Wear Index (Smith & Knight, Br Dent J 1984;157:16). RESULTS: Ecstasy users (n = 30) were compared with non-users (n = 28). Toothwear through the enamel into the underlying dentine occurred in 18 (60%) Ecstasy users but in only three (11%) non-users. The overall mean toothwear score in Ecstasy users was 0.63 compared with 0.16 in non-users (t = 4.34, P < 0.001). Dry mouth was reported by 93% of Ecstasy users whilst 89% stated that they clenched or ground their teeth after taking the drug. Tooth grinding commonly continued into the following morning. Carbonated (acidic) beverages were consumed by 93% of the users with a mean of three cans per "trip". CONCLUSION: The severity of toothwear and the number of teeth affected were greater in Ecstasy users than in a group of non-users. The occlusal surfaces were more commonly affected than the incisal, which may indicate jaw clenching rather than grinding as a feature of Ecstasy-induced muscle hyperactivity.

England↗
PubMed1998

IRT-1, a novel interferon-gamma-responsive transcript encoding a growth-suppressing basic leucine zipper protein.

Interferon-gamma (IFN-gamma) inhibits proliferation of vascular smooth muscle cells (VSMCs) in culture and reduces arterial restenosis post-balloon angioplasty. The identification and characterization of IFN-gamma-specific transcripts in VSMCs are an important approach to discern the molecular mechanisms underlying vascular proliferative disease. In this report, we describe IRT-1, a novel mRNA transcript constitutively expressed in a number of human tissues, but expressed in human VSMCs only when they are stimulated with IFN-gamma. This mRNA expression is induced >200-fold 72 h after IFN-gamma treatment. IRT-1 mRNA is also acutely expressed in rat carotid arteries that are injured by balloon angioplasty. The IRT-1 cDNA transcript encodes a basic protein that contains a leucine zipper motif, a core nuclear localization sequence, and a single strongly hydrophobic region. Constitutive IRT-1 mRNA expression in human peripheral blood lymphocytes is reduced when these cells are stimulated to proliferate. Overexpression of IRT-1 protein in VSMCs alters their morphology and dramatically reduces their proliferative capacity. This study suggests that IRT-1 is an IFN-gamma-inducible factor that may regulate the progression of vascular proliferative diseases.

Amino Acid Sequence↗
PubMed1998

An association between the regular use of 3,4 methylenedioxy-methamphetamine (ecstasy) and excessive wear of the teeth.

AIMS: This study was established to determine if users of ecstasy had greater tooth wear than a comparison group of non-users. DESIGN: The study involved a direct comparison between two groups of young people gathered by a peer information network and divided by the response to the question "Do you take ecstasy?" SETTING: The information network was established at the Maryland Centre in Liverpool (UK). Besides offering advice on drug and sex-related problems this centre distributes free condoms and is therefore visited by many young people who would not consider themselves to have these problems. PARTICIPANTS: There were 30 users and 28 non-users with no significant difference in the gender ratio. Age was not recorded to maintain absolute confidentiality, but all the participants appeared to be of student age. MEASUREMENTS: Tooth wear was measured using the index of Smith & Knight. The social and drug-taking profile of the two groups was ascertained by questionnaire. FINDINGS: It was found that the mean (+/- STD) tooth wear score for the back teeth was 0.96 +/- 0.16 in the users compared with 0.12 +/- 0.08 for the comparison group. These values were significantly different (p < 0.001). The values for the front teeth were not significantly different. Many users were aware of clenching their teeth 12 or even 24 hours after taking the drug. CONCLUSION: Taking ecstasy results in an increased likelihood of tooth wear on the back teeth. This is likely to result from clenching the teeth in the acidic environment caused by carbonated (fizzy) drinks.

Drinking↗
PubMed1998

Endosulfan poisoning in Northern India: a report of 18 cases.

Eighteen cases of endosulfan poisoning by accidental overexposure during spray, admitted between October 1995 to September 1997, were observed and analyzed. These accounted for approximately one third of the total number of poisoning cases admitted in our unit during this period. Nausea, vomiting abdominal discomfort, tonic and clonic convulsions, confusion, disorientation, and muscular twitchings were cardinal manifestations. None of the patients succumbed to their illness. Analysis of various incriminating factors revealed that accidental overexposure was due to failure to adhere to the instructions for spray either due to ignorance or due to illiteracy. All the patients avoided preventive measures and developed toxicity both due to inhalation and absorption through skin. Endosulfan (a chlordiene derivative) poisoning is gaining up momentum in this part of world and has become an important matter for public health in India.

Accidents↗
PubMed1997

Effect of active-site modification on the terminal marking deamidation of triosephosphate isomerase.

The conformational change which results from the opening and closing of the hinged lid over the catalytic center of triosephosphate isomerase is transmitted to the subunit interface of the dimer and eventually leads to the spontaneous, specific deamidation of Asn71. This is followed by the deamidation of Asn15 approximately 5 A away on the neighboring subunit and leads to destabilization of the protein and degradation. However, it has not been established whether this molecular wear and tear occurs via an intra-subunit or inter-subunit transmission of the conformational change. We have studied this first step in the terminal marking by reacting the active-site Glu165 with the substrate analog 3-chloroacetol phosphate (CAP) which immobilizes the hinged lid. Under mild deamidation conditions (pH 9.5, 24 h, 30 degrees C) the native homodimer readily deamidated. In contrast, the CAP-modified homodimers were resistant to deamidation. Heterodimers composed of one native subunit and one CAP subunit showed intermediate deamidation. When the native and CAP-labeled subunits were resolved by electrophoresis in urea gels, it was found that the unlabeled subunit had preferentially deamidated. These data coupled with molecular modeling considerations show that restricting movement of the hinged lid prevents deamidation of Asn71 on that subunit, but that the other subunit with the free hinged lid functions independently and still deamidates. Thus, the conformationally induced wear and tear appears to be largely intra-subunit. These observations clearly link catalysis with terminal marking of the protein and suggest a general mechanism for how other enzymes may wear out.

Amides↗
PubMed1997

Aneurysms of sinus of Valsalva eroding into the interventricular septum: etiopathology and surgical considerations.

OBJECTIVE: To evaluate and discuss etiopathology, clinical manifestations and surgical outcome of a rare subset of unruptured aneurysm of the sinus of Valsalva which erodes into the interventricular septum. METHODS: Between 1989 and 1995, seven cases of unruptured aneurysm of the sinus of Valsalva eroding into the interventricular septum underwent surgical correction at the King Edward VII Memorial Hospital, Bombay. The origin of all these aneurysms was from the right coronary sinus. The mean age of presentation was 31 years. All patients were male. Calcification of the aneurysm was seen in three. Three patients presented without aortic regurgitation; all had complete heart block. Four patients presented with aortic regurgitation and in addition, two had complete heart block. Preoperative left ventricular function was poor in patients with aortic regurgitation (Ejection fraction range; 30-42%), when compared to those without aortic regurgitation (Ejection fraction range; 48-52%). Of those without aortic regurgitation at initial presentation, one patient developed progressive aortic regurgitation after 3 years requiring surgery. While two other patients were operated at earliest for closure of aneurysm, even in the absence of aortic regurgitation. All those with aortic regurgitation required surgery for aortic valve replacement and closure of aneurysm. Aneurysm was closed by direct suturing of the ostium in two patients and by patch closure in five patients. Permanent pacemaker was implanted in five patients. RESULT: There was no operative death. Patients who underwent aortic valve replacement required postoperative ionotropic support. Two patients, who underwent surgery in absence of aortic regurgitation, remain free of aortic regurgitation at the end of 36 and 42 months of follow-up. One of the patients with calcific aneurysmal sac underwent successful re-replacement of the aortic valve for paravalvar leak after a 2 year interval. CONCLUSION: Unruptured aneurysm of the sinus of Valsalva eroding into the interventricular septum should be operated at the earliest, which makes surgery simple and prevents development of complications such as aortic regurgitation and heart block.

Adult↗
PubMed1996

Pseudohexabothrium taeniurae n. sp. (Monogenea: Hexabothriidae) from the gills of Taeniura lymma (Dasyatididae) from the Great Barrier Reef, Australia.

Pseudohexabothrium taeniurae n. sp. is proposed for a hexabothriid monogenean found on the gills of Taeniura lymma (Forsskål) off Heron Island, Great Barrier Reef, Queensland, Australia. Pseudohexabothrium taeniurae is distinguished from Pseudohexabothrium rajae Brinkmann, 1952, the type and only species of the genus, by the morphology of the sucker sclerites and eggs, and by the size of the hamuli, pharynx, and the "false" oral sucker. The generic diagnosis of Pseudohexabothrium is revised. A phylogenetic analysis places Pseudohexabothrium as the sister group to the rest of the family except Hexabothrium.

Animals↗
PubMed1995

Neoplastic transformation and aberrant cell-cell interactions in genetic mosaics of lethal(2)giant larvae (lgl), a tumor suppressor gene of Drosophila.

Homozygosity for lethal(2)giant larvae (lgl), a mutation in a tumor suppressor gene of Drosophila, induces neoplasia of the imaginal discs. To explore the developmental capacities of lgl mutant cells, we have investigated their growth and differentiation in genetic mosaics. Adult wings mosaic for lgl displayed abnormal growth and differentiation of the lgl mutant and neighboring wild-type cells, suggesting aberrant cell-cell interactions during development. lgl mutant clones also straddled the anteroposterior boundary of the wing imaginal disc, apparently due to failure of the cells of the anterior and the posterior compartment to segregate at the boundary. To further test if anteroposterior compartmentalization takes place in the neoplastic imaginal discs of lgl mutant larvae, we studied the expression of an engrailed (en)-specific lacZ reporter gene during progressive stages of their tumorous growth. Our results show that en is activated in the posterior compartments of the neoplastic imaginal discs. However, during later stages of tumorous overgrowth, the en-expressing and nonexpressing cells appear to show extensive intermixing. These observations suggest that neoplastic transformation of imaginal discs involves loss of their normal cell-cell interactions and signaling.

Animals↗
PubMed1995

Epithelial hyperplasia of imaginal discs induced by mutations in Drosophila tumor suppressor genes: growth and pattern formation in genetic mosaics.

Lethal mutations in the giant discs (lgd) and fat (ft) tumor suppressor genes of Drosophila cause epithelial hyperplasia in all imaginal discs. By contrast, mutations in the vestigial (vg) gene adversely affect cell viability in the wing imaginal discs and consequently cause loss of pattern in the adult wings. However, combining homozygous lgd or ft mutations with homozygous vg1 increases the size of the wing imaginal discs and partially restores the bristle pattern in the wings of pharate adults. Comparable pattern restoration in vg1 wings is also induced by a newly isolated weak hypomorphic lgd3 allele. Further, mosaic analysis revealed that whereas lgd clones generated by the Minute technique display abnormal differentiation, those induced in a homozygous vg1 background exhibit autonomous restoration of wing pattern. These results suggest that pattern restoration in vg1 wings can serve as an assay for hyperplasia induced by mutations in Drosophila tumor suppressor genes.

Animals↗
PubMed1994

Mitochondrial gene expression during bovine cardiac growth and development.

The expression of both mitochondrial and nuclear genes encoding enzymes involved in electron transport and oxidative phosphorylation was examined in bovine cardiac tissue during early growth, development and aging. The steady state level of mRNAs for mitochondrial genes including ATPase 6. COXII and cyt b increased 2.5-4-fold relative to early fetal levels in late fetal and young adult tissues and showed a marked decline (30-50%) in older adult tissues. Similar results were found with the nuclear genes, COXVB and ATP-beta synthase showing coordinate regulation of the two genomes. An increase in mtDNA copy number correlated with the increase in transcript level. Enzyme activity levels for NADH dehydrogenase and cytochrome c oxidase showed a similar trend, albeit of lesser magnitude. These activity levels contrasted with the activity level of an entirely nuclear-encoded mitochondrial enzyme, citrate synthase, which increased not only throughout development but in the older adult tissue. This study indicates that there is a pattern of increasing mitochondrial and nuclear gene expression for OXPHOS enzymes in developing cardiac tissue and decreasing OXPHOS gene expression in the aging heart.

Animals↗
PubMed1991

Misoprostol but not antacid prevents endotoxin-induced gastric mucosal injury: role of tumor necrosis factor-alpha.

Many of the complications of septic shock are believed to be a consequence of elevated circulating levels of tumor necrosis factor (TNF), which is an important mediator of tissue injury. Prostaglandins (PGs) of the E series have recently been reported to inhibit TNF production in vitro. We investigated the in vivo effect of misoprostol, a PGE1 analog, on endotoxin-induced gastric mucosal injury and TNF production. For the gastric mucosal injury studies, groups of animals were pretreated with intragastric misoprostol (100 and 200 micrograms/kg) or with antacid (2 ml/animal of Maalox Plus) 30 min prior to a challenge with intravenous E. coli lipopolysaccharide (LPS) at 5.0 mg/kg. Stomachs were examined 3 hr after LPS. Systemic endotoxin alone induced microscopic edema, vascular congestion, and polymorphonuclear (PMN) infiltration of the gastric mucosa. Pretreatment with misoprostol, but not with antacid, significantly and dose-dependently reduced the gastric mucosal injury. For the TNF studies, groups of rats were given either misoprostol (100 or 200 micrograms/kg, intragastric), or saline 1 hr prior to LPS challenge. Serum samples were obtained 1.5 hr after LPS challenge. Misoprostol dose-dependently and significantly (P less than 0.01) inhibited TNF activity. We conclude that misoprostol is a potent inhibitor of TNF systemic production and inhibits the gastric mucosal injury induced by endotoxemia. These studies suggest a potentially important therapeutic role for misoprostol in inflammatory diseases in which TNF exerts a contributory role.

Aluminum Hydroxide↗
PubMed1991

QSAR studies on benzodiazepine receptor binding of purines and amino acid derivatives.

Quantitative structure-activity relationship (QSAR) studies are reported on the benzodiazepine receptor binding of a series of substituted 9-benzyl-6-dimethylamino-9H-purines and N-(indol-3-ylglyoxylyl)amino acid derivatives. The nitrogen of the five membered heterocyclic ring and the polar substituent in the aromatic ring, present in both series of compounds, form important centres in the binding interaction. We conclude that the receptor must possess a strong nucleophilic centre and a polar site, and that a hydrophobic pocket exists to accommodate hydrophobic moieties.

Algorithms↗
PubMed1991

Risk factors for gastrointestinal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs)

Thirteen million individuals in the United States take nonsteroidal anti-inflammatory drugs (NSAIDs) chronically for the relief of pain and inflammation caused by arthritis and related conditions. NSAIDs are valuable and in many cases essential to the management of arthritis pain. Long-term use of NSAIDs, however, can cause gastrointestinal (GI) ulcers and potentially life-threatening ulcer complications. Factors such as older age (greater than or equal to 60 years), a history of peptic ulcer disease, concomitant corticosterid use, cigarette smoking, alcohol use, and high dose or multiple NSAID therapy can increase the risk of GI damage and complications in the chronic NSAID user. Physician awareness of these risk factors is crucial so that the benefits and hazards of NSAID therapy in high-risk patients can be properly weighed. When the decision is made to prescribe NSAIDs, despite the presence of risk factors for NSAID-induced ulcers, patients should be closely monitored, and, in some cases, effective prophylaxis should be initiated. This is especially important since NSAID-induced gastrointestinal ulcers can be asymptomatic, causing serious ulcer complications without warning.

Aged↗
PubMed1989

Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin.

High-dose aspirin therapy for rheumatoid arthritis is frequently associated with severe gastrointestinal injury. To explore the possibility of reversing such damage, we conducted a double-blind, multicenter study with misoprostol, a prostaglandin E1 analog, which has demonstrated mucosal protective, gastric antisecretory, and ulcer healing properties. We also studied possible interference of misoprostol with continuing aspirin treatment in the management of patients with rheumatoid arthritis. Patients with confirmed rheumatoid arthritis and endoscopically documented gastroduodenal lesions were randomly assigned to receive 200 micrograms of misoprostol four times a day (123 patients) or placebo (116 patients). Each concurrently received 650 to 1300 mg of aspirin four times a day. After eight weeks of treatment, misoprostol was statistically superior to placebo in healing gastric mucosal injury (70% vs 25%) and duodenal mucosal injury (86% vs 53%). Patients with gastric or duodenal ulcers on admission had superior ulcer healing rates with misoprostol (67% vs 26%). There was no evidence of interference with the antirheumatic properties of aspirin. Mild to moderate adverse experiences were equally noted in misoprostol and placebo groups. Misoprostol, coadministered with aspirin, is well tolerated and highly effective in healing aspirin-associated gastroduodenal lesions in patients with rheumatoid arthritis without altering the therapeutic benefits of aspirin.

Adult↗