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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 505 records · Page 28Linked to original sources

Topical ketorolac 0.5% solution for the treatment of vernal keratoconjunctivitis.

The efficacy of topical ketorolac 0.5% in treatment of vernal keratoconjunctivitis (VKC) was evaluated in a randomised double-blind prospective trial in 21 patients. Ketorolac treated eyes showed 50.7% reduction in main symptoms of itching compared to 33.3% relief in placebo treated eyes after 2 weeks of treatment (p < 0.01). Photophobia, ropy discharge, and conjunctival injection also lessened by 39.9%, 31.6%, and 39.1%, respectively, in ketorolac treated eyes compared to 23.8%, 17.3%, and 20.3% in placebo group. Transient stinging sensation was observed in 3 (14.3%) patients on ketorolac therapy. This study shows efficacy of ketorolac 0.5% solution in controlling symptoms in VKC.

Administration, Topical↗

Primary argon laser trabeculoplasty vs pilocarpine 2% in primary open angle glaucoma: two years follow-up study.

In a prospective study, the efficacy of argon laser trabeculoplasty (ALT) was evaluated and compared with pilocarpine 2% as primary treatment in newly diagnosed primary open angle glaucoma (POAG). Out of 38 patients with POAG included in this study, one eye each of 36 patients underwent ALT, and one eye each of 26 patients received pilocarpine 2% every 8 hours. The mean pre-treatment IOP was 25.48 +/- 4.13 mmHg in ALT group and 24.47 +/- 3.51 mmHg in the pilocarpine group. The mean post treatment IOP at 2 year follow was 18.2 +/- 2.55 mmHg in ALT group and 18.27 +/- 2.22 mmHg in the pilocarpine group. Post treatment IOP was significantly lower than pre-treatment IOP in both ALT and pilocarpine groups. The post treatment fall in IOP showed no significant difference in ALT versus pilocarpine 2% at various follow up intervals (p > 0.05). This study showed equal efficacy of ALT and pilocarpine 2% as initial therapy of POAG.

Administration, Topical↗

A critical evaluation of anti-peroxidant effect of intravenous magnesium in acute aluminium phosphide poisoning.

The anti-peroxidant effect of intravenous magnesium was evaluated in 50 patients with acute aluminium phosphide poisoning. The patients were divided into two groups, one who received magnesium sulphate therapy (Group I) and the other who did not (Group II). The clinical and biochemical parameters in both groups were comparable. Finding of increased mean malonyl-di-aldehyde (MDA) levels in group I (3.18 +/- 0.93 micromol/L) and group II (3.15 +/- 0.78 mmol/L) combined with low blood levels of reduced glutathione (18.5 +/- 1.6 mg/dl in group I) and (17.8 +/- 1.4 mg/dl in group II) indicated oxidative stress leading to accelerated lipid peroxidation in the early phase (0-6 h) of AlP poisoning. A significant fall in MDA levels was observed after 2 h in the magnesium treated group (group I) compared to the non-treated group (group II) and levels became normal between 48-72 h. Similarly reduced glutathione started recovering between 12-24 h which became significant after 24 h and full recovery took place between 48-72 h in the magnesium treated group (group I). Both these parameters suggested an anti-peroxidant effect of magnesium. There was also a slight fall in MDA levels and a rise in reduced glutathione in the non-treated group II patients. This could be due to elimination of phosphine (PH3). We hypothesize that oxidative stress in AlP poisoning buffered the magnesium leading to a transient fall in magnesium and magnesium dependent GSH, resulting in increased susceptibility of oxygen free radical injury and accelerated lipid peroxidation. The fall in MDA and slower rise in GSH in group I than in group II suggested magnesium combated free radical stress slowly and independent of elimination of phosphine. This hypothesis was further strengthened by similar observations when both these parameters were compared in survivors in both groups. Mortality was higher in group II than in group I (44 per cent vs 20 per cent) and was probably related directly to oxidative stress.

Adolescent↗

In vitro comparison of restoration wear and tensile strength following extended brushing with Sonicare and a manual toothbrush.

The purpose of this study was to compare the wear, cement margin breakdown and bond strength of restorations following 6 to 12 months of simulated use in vitro of the Sonicare and a manual toothbrush. Extracted molar teeth with Class V hybrid composite resin restorations (n = 21) or with Class V gold inlays cemented with zinc phosphate cement were tested for wear and marginal integrity following brushing for a period that simulated 6 months of typical use. One-third of the molars in each group were brushed with the Sonicare and one-third were brushed with the manual brush. The remaining third served as non-treated controls. Toothbrushing was performed under a standardized load using a piston-action brushing machine. After brushing, the enamel, dentin/cementum and restorations were examined by light and scanning electron microscopy. There was no apparent wear of tooth structure or of restorative materials with either the Sonicare or the manual brush. There was a small loss of cement from the margins of the gold inlays following toothbrushing, which was similar and not significantly different between the sonic and manual brush. To test brushing effects on crown retention, four identical metal dies were prepared to simulate premolar crown preparations. Thirty cast copings, prepared to fit the dies, were cemented with zinc phosphate cement. Toothbrushing with Sonicare or the manual toothbrush was performed as before (n = 15 for each brush), but the simulated time was extended to the equivalent of 1 year of brushing. The dislodgement force of cemented crowns was not significantly different (t-test, p > 0.10) between the manual (207 +/- 69 N) and Sonicare (221 +/- 61 N) groups. These results demonstrate that despite its high frequency bristle motion, Sonicare exerts no detrimental effects on cement margin integrity, crown bond strength or surface wear of dental and restorative materials.

Analysis of Variance↗

Effects of BN-50730 (PAF receptor antagonist) and physostigmine (AChE inhibitor) on learning and memory in mice.

The present study was designed to investigate the effect of BN-50730, a PAF receptor antagonist, on learning and memory in mice using elevated plus-maze and to delineate the role of acetylcholine in modulating the effect of PAF receptor antagonist on learning and memory. BN-50730 administered immediately after plus-maze training on day 1 induced retrograde amnesia as indicated by a dose-dependent increase in transfer latency (TL) measured on day 2 whereas no such increase in TL was noted when BN-50730 (2.5 mg/kg, i.p.) was administered prior to plus-maze training. Physostigmine (0.5 mg/kg; 1.0 mg/kg, i.p.) administered 30 min prior to plus-maze training attenuated BN-50730-induced increase in TL measured on day 2. These results suggest that BN-50730, a PAF receptor antagonist, produced retrograde amnesia and physostigmine attenuated BN-50730-induced amnesia possibly through increased concentration of cerebral acetylcholine and a consequent increase in PAF release.

Acetylcholine↗

Pharmacological basis of drug therapy of Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative disorder primarily manifesting as a loss of memory. Senile plaques and neurofibrillary tangles are the major histopathological alteration in the brain of Alzheimer's disease patients. A considerable deficiency of cholinergic neurons is a consistent finding in Alzheimer's disease. Therefore, many therapeutic strategies to augment cerebral concentration of acetylcholine such as cholinergic precursors, cholinergic receptor agonists, cholinesterase inhibitors and acetylcholine release modulators have been evaluated in Alzheimer's disease. Although cholinesterase inhibitors such as tacrine and galanthamine offer modest clinical benefits, other cholinergic agents have proved to be of limited therapeutic value. Efforts to enhance monoaminergic neurotransmission have also been largely disappointing. Therefore, emphasis is not being put on the use of combination of two class of drugs. Moreover, use of therapeutic agents based on the putative pathogenic etiology of the disease such as excitotoxicity, amyloidosis, aluminium accumulation, inflammatory mechanisms and free radical production is being evaluated. Desferrioxamine, non-steroidal anti-inflammatory drugs, prednisone, dapsone, vitamin E and idebenone are some such agents that are currently under investigation for the preventive or palliative effect in Alzheimer's disease. Neurotrophic factors such as nerve growth factor, brain derived neurotrophic factor and epidermal growth factor have shown promising results in animal studies. However, novel methods for delivering these molecules into the brain required to be developed before launching their clinical trials in man.

Alzheimer Disease↗

Effect of ibuprofen and diclofenac sodium on experimental would healing.

Effects of frequently used anti-inflammatory drugs ibuprofen and diclofenac was studied on experimental wound healing in rats. These drugs impede tissue repair by virtue of retarding inflammation. There was 16-36% reduction in wound strength measured in terms of tensile strength in experimental rats. The detrimental effect of anti-inflammatory drugs was confirmed by histological examination of wound and by measuring dry granuloma weight.

Animals↗

Abuse of codeine-containing cough syrups: a report from India.

AIM: To study the socio-demographic and clinical profile of patients seeking treatment for abuse of codeine-containing cough syrups (CCS). DESIGN: Observational; case series. SETTING: An addiction clinic in North India. PARTICIPANTS: Forty-six consecutive treatment-seeking patients of DSM-III-R-diagnosed dependence on CCS, from January 1994 to June 1995. MEASUREMENTS: Semi-structured interview schedule for patients and their family covering socio-demographic and clinical variables. FINDINGS: All patients were male. Many were young (mean age 27 years), with completed school education (85%) and from urban backgrounds (80%). The mean age of starting CCS use was 23 years. Initiated commonly through friends (89%) and often for curiosity (63%), 89% of the patients progressed to daily use of CCS in less than 6 months (54% in less than a month), and in quantities much higher than prescribed limits. Opioid-like withdrawal was reported by 92%. Concurrent use of other substances, psychiatric co-morbidity and HIV-related risk behaviour were present in 72%, 24% and 45%, respectively. Most of the patients reported a 'stimulant' effect of CCS ('alert', 96%; 'more active', 94%). CONCLUSIONS: The combination of an opioid and a sympathomimetic agent in the CCS may cause a special, distinct euphoretic effect. This effect, along with the low price, easy availability and 'pure' preparation of CCS, may be responsible for the rapidly rising popularity of the CCS as drugs of abuse in India.

Adolescent↗

Suture splint: an alternative for luxation injuries of teeth in pediatric patients--a case report.

Stabilization of replanted tooth "splinting" is done to prevent further damage to the pulp and periodontal structure during the healing period. Suture and bonded resin splint is passive, semirigid and functional splint. It is easy to fabricate directly in mouth without lengthy laboratory procedures. A case is presented in which suture and bonded resin splint was performed on laterally luxated maxillary central incisor and avulsed lateral incisor. The splint was removed after one week and sufficient periodontal and gingival healing was observed.

Adolescent↗

all-trans retinoic acid enhances cisplatin-induced apoptosis in human ovarian adenocarcinoma and in squamous head and neck cancer cells.

Cisplatin exerts its cytotoxicity by inducing apoptosis. Similarly, all-trans retinoic acid (ATRA) causes apoptosis in certain cells. We studied the interaction of cisplatin and ATRA in human ovarian adenocarcinoma cells 2008, in human head and neck squamous carcinoma cells UMSCC10b, and in their respective cisplatin-resistant sub-lines. ATRA enhanced the cytotoxicity of cisplatin. The interaction of the drugs was synergistic in combination index-isobologram analyses (combination index >0.5 at 50% cell survival) in all of the cell lines tested. ATRA inhibited the cellular accumulation of the cisplatin analogue [3H] cis-dichloroethylenediamineplatinum(II) by 22-33% in three of four cell lines tested but did not alter the cellular content of reduced glutathione. The expression of Bcl-2 relative to Bax decreased more after combined treatment with cisplatin and ATRA than after either drug alone. The apoptotic mechanism of cell death was confirmed by demonstrating cleavage of poly(ADP-ribose)polymerase and by morphological analysis. The combined treatment with ATRA and cisplatin induced apoptosis in significantly more cells than either drug alone. We conclude that ATRA enhances the cytotoxicity of cisplatin by facilitating apoptosis in ovarian and head and neck carcinoma cells.

Adenocarcinoma↗

Antitumor efficacy of N1,N11-diethylnorspermine on a human bladder tumor xenograft in nude athymic mice.

The spermine analogue N1,N11-diethylnorspermine (DENSPM) has been shown to induce the polyamine-acetylating enzyme spermidine/spermine N1-acetyltransferase, disrupt polyamine pool homeostasis, and inhibit tumor growth. DENSPM is currently being developed as an anti-neoplastic agent and is about to enter Phase II clinical trials. In this report, the antitumor efficacy of DENSPM was evaluated against a human transitional cell bladder BL13 carcinoma xenograft implanted orthotopically and s.c. in nude athymic mice. DENSPM was administered via continuous s.c. infusion at 93 mg/kg/day for 5 days. Treatment with DENSPM was well tolerated and produced tumor regressions in all mice with a significant proportion (up to 50%) of apparent cures. On the basis of low toxicity and good therapeutic efficacy, there is a strong rationale for evaluation of the therapeutic efficacy of DENSPM against bladder carcinomas in Phase II clinical trials.

Animals↗

Phenethyl isothiocyanate modulates clastogenicity of mitomycin C and cyclophosphamide in vivo.

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is an effective chemopreventive agent against N-nitrosamine-induced carcinogenesis. We have investigated the extent to which PEITC modulates the clastogenicity of standard genotoxicants, mitomycin C and cyclophosphamide, using bone marrow cells of Swiss albino mice. PEITC, 1 mumol/kg body weight in corn oil was administered by gavage for 7 consecutive days to prime the animals. 24 h later, mice received a single dose of cyclophosphamide (10 or 20 mg/kg body weight) or mitomycin C (1 or 2 mg/kg body weight) intraperitoneally. Clastogenicity of the chemicals was compared using PEITC-primed and non-primed animals 24 h after clastogen treatment. As a single agent, PEITC is not clastogenic even after 7 days of priming. Oral priming with PEITC decreased the aberrations per cell values by 22-67% in all cases. PEITC could only alleviate the clastogenicity of 1 mg/kg body weight mitomycin C to near-control values (p < or = 0.05). Although PEITC is reported to be effective against N-nitrosamine-induced tumorigenesis by preventing metabolic activation and by blocking the reactive species formed, it is virtually ineffective against the clastogenicity of cyclophosphamide. The results of inhibition by PEITC of the clastogenicity of mitomycin C suggest that the modulation of mitomycin C bio-activation contributes to, but may not be sufficient for, PEITC chemoprevention of clastogenicity by mitomycin C.

Animals↗

Paclitaxel-liposomes for intracavitary therapy of intraperitoneal P388 leukemia.

Paclitaxel, a recently approved antineoplastic agent, is cleared slowly from the peritoneal cavity after i.p. injection, and therefore appears to be promising for intracavitary therapy of malignancies confined to the peritoneal cavity. However the dose-limiting toxicity of Taxol, the clinical formulation of paclitaxel, was severe abdominal pain, likely caused by the excipients (Cremophor EL and ethanol) that are required to overcome low drug solubility. We tested the hypothesis that a liposome-based formulation could modulate paclitaxel toxicity independent of antitumor activity. The dose-dependence of toxicity and antitumor effect of paclitaxel liposomes was evaluated after i.p. administration against i.p. P388 leukemia. Liposomal paclitaxel showed antitumor activity similar to that of free paclitaxel (as Taxol), but was better tolerated by both healthy and tumor-bearing mice.

Animals↗

Chlorophyll and chromosome breakage.

Increased consumption of green vegetables in the diet has been associated with protection against carcinogenic effects and related mutagenic and clastogenic (chromosome breaking) activity of genotoxic agents. Chlorophyll, present in all green plant parts, has been suggested to be a major protective factor in the process. We have, however, observed that while a crude aqueous extract of Indian spinach leaf significantly reduced genotoxic effects, chlorophyll alone was ineffective. On the other hand, chlorophyll, both as an aqueous extract from the leaf and in a purified commercial form, induced a significantly high frequency of chromosome breaks in bone marrow cells of mice on oral administration. The crude aqueous extract of the leaf was non-toxic. The protective activity of the crude leaf extract may be attributed to the total effect of the interaction between different components, in which the clastogenicity of chlorophyll has been neutralized.

Administration, Oral↗

Reduction in the level of Gal(alpha1,3)Gal in transgenic mice and pigs by the expression of an alpha(1,2)fucosyltransferase.

Hyperacute rejection of a porcine organ by higher primates is initiated by the binding of xenoreactive natural antibodies of the recipient to blood vessels in the graft leading to complement activation. The majority of these antibodies recognize the carbohydrate structure Gal(alphal,3)Gal (gal epitope) present on cells of pigs. It is possible that the removal or lowering of the number of gal epitopes on the graft endothelium could prevent hyperacute rejection. The Gal(alpha1,3) Gal structure is formed by the enzyme Galbeta1,4GlcNAc3-alpha-D-galactosyltransferase [alpha(1,3)GT; EC 2.4.1.51], which transfers a galactose molecule to terminal N-acetyllactosamine (N-lac) present on various glycoproteins and glycolipids. The N-lac structure might be utilized as an acceptor by other glycosyltransferases such as Galbeta1,4GlcNAc 6-alpha-D-sialyltransferase [alpha(2,6)ST], Galbeta1,4GlcNAc 3-alpha-D-Sialyltransferase [alpha(2,3)ST], or Galbeta 2-alpha-L-fucosyltransferase [alpha(1,2)FT; EC 2.4.1.691, etc. In this report we describe the competition between alpha(1,2)FT and alpha(1,3)GT in cells in culture and the generation of transgenic mice and transgenic pigs that express alpha(1,2)Fr leading to synthesis of Fucalpha,2Galbeta- (H antigen) and a concomitant decrease in the level of Gal(alpha1,3)Gal. As predicted, this resulted in reduced binding of xenoreactive natural antibodies to endothelial cells of transgenic mice and protection from complement mediated lysis.

Animals↗