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Biomedical subjects

M Gupta

Publications and source records attributed to M Gupta.

At least 55 records · Page 3Linked to original sources

Anti-steroidogenic activity of the two Indian medicinal plants in mice.

The chloroform extract of Croton roxburghii bark (CECR, Euphorbiaceae) and ethyl acetate extract of Zizyphus jujuba bark (EAZJ, Rhamnaceae) were evaluated for anti-steroidogenic activity in the adult female mouse. This study was designed to assess the effects of CECR and EAZJ on ovarian steroidogenisis. Antifertility activity was evaluated by observing the estrus cycle, body weight, wet weight of ovaries, steroidogenic enzymes, and substrates. Blood profiles were estimated to find out the toxic manifestations of the extracts. CECR and EAZJ each arrested the normal estrus cycle of adult female mouse at diestrus stage and reduced the wet weight of ovaries significantly. Cholesterol and ascorbic acid content in ovaries of crude extract-treated mice were significantly elevated. The significant inhibition of delta(5)-3beta-hydroxysteroid dehydrogenase (delta(5)-3beta-HSD) and glucose-6-phosphate dehydrogenase (G-6-PDH), the two key enzymes involved in ovarian steroidogenisis, were also observed in mouse after 18 days of treatment. Hematological profiles, biochemical estimations of whole blood and serum remains unaltered in extract-treated mouse. Normal estrus cycle and ovarian steroidogenisis were restored after withdrawal of treatment with CECR and EAZJ on average 27 and 32 days, respectively. Antifertility activities of crude extracts were found to be reversible.

3-Hydroxysteroid Dehydrogenases↗

Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency.

Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to pharmacologic rescue, at 3-4 weeks of life. In the current report, we characterized amino acid profiles in SSADH(-/-) brain utilizing whole brain and regional extracts (frontal and parietal cortex, hippocampus, and cerebellum) to develop hypotheses concerning epileptogenesis. Of 35 amino acids quantified, we found significant dysregulation in SSADH(-/-) mice for 11 (GABA, glutamate, glutamine, alanine, aspartate, serine, taurine, cystathionine, methionine, homocarnosine, and arginine) as compared to age-matched littermates both before, and following, the period of generalized convulsive seizures and status epilepticus. Our results reveal imbalanced amino acid levels potentially involved in the transition from absence seizures to generalized convulsive seizures resulting in SSADH(-/-) mice. We conclude that the SSADH(-/-) mouse represents a unique epileptic model with the potential to reveal novel aspects of excitatory/inhibitory interactions in the genesis of seizures.

Aldehyde Oxidoreductases↗

Efficacy of photodynamic therapy in circumscribed choroidal haemangioma.

PURPOSE: To report efficacy of photodynamic therapy (PDT) in the treatment of three cases of juxtafoveal circumscribed choroidal haemangioma. METHODS: Data on three patients (two primary, and one failed TTT) treated with verteporfin, 6 mg/m2 given as i.v. infusion over 10 min. Diode laser (690 nm) with an intensity of 600 mW/cm2 for 83 s (50 mJ/cm2) was applied 5 min after completion of infusion. Overlapping multiple spots (2500 microm) were applied to cover the entire surface of the tumour. The mean pretreatment tumour size was 7 mm (base) x 2.2 (thickness) mm. Periodic follow-up with ophthalmoscopy, ultrasonography, and angiographic studies was performed. RESULTS: All three cases showed complete regression of the tumour with resolution of subretinal fluid, flattening of tumour, and absence of choroidal vasculature on ICG. The visual acuity either improved or remained stable in all three cases. The overlying retinal vessels remained unaffected. There were no ocular or systemic complications. CONCLUSIONS: PDT is an effective treatment for management of juxtafoveal circumscribed choroidal haemangioma.

Choroid Neoplasms↗

Endoscopic biopsies from normal-appearing terminal ileum and cecum in patients with suspected colonic tuberculosis.

BACKGROUND AND STUDY AIMS: Colonic tuberculosis is generally diagnosed by colonoscopy and targeted biopsy of lesions. However, the diagnostic yield of colonic biopsies is not very good. So far as we are aware, there have been no studies investigating the role of biopsies from endoscopically normal-appearing cecum and terminal ileum in diagnosing colonic or ileal tuberculosis, or both. PATIENTS AND METHODS: Patients with a clinical suspicion of colonic tuberculosis, in whom no endoscopic abnormalities were found on colonoscopy or ileoscopy, were included in the study. Multiple biopsies were obtained from the cecum and ileum. RESULTS: Fifty patients were studied. Intubation of the terminal ileum was possible in 43 patients (86 %). Histological examination of biopsies obtained from the cecum and terminal ileum showed noncaseating granuloma in two patients. Both of these biopsies were from the terminal ileum. In two other patients, collections of loosely arranged epithelioid cells were observed. This established the diagnosis in these four patients (8 %). In the remaining 46 patients, histology showed nonspecific inflammation in 18 patients (in the cecum in 15 and in the terminal ileum in seven). The other biopsies did not show any abnormalities (33 from the cecum, 34 from the terminal ileum). CONCLUSIONS: Histological examination of biopsies from the normal-appearing cecum and terminal ileum is useful in a small but significant number of patients with colonic tuberculosis.

Adult↗

Acute myeloid leukemia following treatment with cladribine for hairy cell leukemia: a case report and review of the literature.

The overall survival of patients with hairy cell leukemia (HCL) has significantly increased in recent years because of the development of effective treatments such as interferon alpha and purine analogs. Several reports have described an increased risk of secondary cancers, particularly solid tumors, in patients with HCL. We describe a case of a patient with HCL, who had prolonged pancytopenia after a single course of cladribine. Fifteen months after the diagnosis of HCL the patient developed acute myeloid leukemia (AML) and died shortly afterwards. Review of the literature shows few reports of acute leukemia in HCL patients. All of the 11 reported cases of leukemia in patients with HCL have been in patients who have been treated with either interferon alpha or purine analogs, and developed several years (mean 4.3 years; range 1.6-6.4 years) after the diagnosis of HCL. Our case is unusual in that the patient developed AML shortly (1.2 years) after the diagnosis and treatment of HCL. Further studies are needed to clarify whether leukemias seen in patients following the treatment of their HCL are incidental findings or related to HCL and its treatments.

Acute Disease↗

Photodynamic therapy of circumscribed choroidal haemangioma.

AIM: To evaluate efficacy of verteporfin ocular photodynamic therapy (PDT) in treatment of 10 patients with a symptomatic circumscribed choroidal haemangioma. DESIGN: Prospective non-randomised, interventional case series and critical review of previously published studies. METHODS: 10 consecutive patients (seven primary, two failed transpupillary thermotherapy (TTT), and one failed external beam radiotherapy) with symptomatic circumscribed choroidal haemangioma were treated using verteporfin 6 mg/m2 given as an intravenous infusion over 10 minutes. Diode laser (690 nm) with an intensity of 600 mW/cm2 for 83 seconds (50 J/cm2) was applied 5 minutes after completion of infusion. Single or multiple partially overlapping spots were applied based on the tumour basal dimensions. Periodic follow up with ophthalmoscopy, ultrasonography, and angiographic studies was performed. RESULTS: All 10 patients showed evidence of regression with flattening of tumour, resolution of subretinal fluid, and reduction of choroidal vasculature on angiograms. The visual acuity either improved or remained stable in eight (80%) patients. Visual loss due to delayed choroidal atrophy was seen in two patients. CONCLUSIONS: Although verteporfin PDT is an effective treatment for management of symptomatic circumscribed choroidal haemangioma, delayed treatment related effects can lead to visual loss.

Adult↗

Evaluation of analgesic, antipyretic activity and toxicity study of Bryonia laciniosa in mice and rats.

Analgesic, antipyretic activity and toxicity study of the leaves of Bryonia laciniosa Linn. (Family: Cucurbitaceae) was evaluated in the standard animal models. The methanol extract of Bryonia laciniosa (MEBL) was evaluated by hot plate and acetic acid-induced writhing methods to assess analgesic activity. The antipyretic activity of the extract was also evaluated by normal body temperature and yeast-induced hyperpyrexia. The extract showed significant analgesic and antipyretic activity. The MEBL was further evaluated for toxicity at the doses of 125 and 250 mg/kg administered orally for 14 days in rats. At the end of experiments, the blood, liver function and kidney metabolism were observed. The hematological profile and different biochemical parameters such as SGOT, SGPT and ALP were estimated. The present study revealed that MEBL exhibited significant analgesic and antipyretic activity in the tested experimental animal models. The toxicity study indicates that the extract is not toxic at the tested doses.

Alanine Transaminase↗

Frequency of MICA in all babies in southeast Sweden (ABIS) positive for high-risk HLA-DQ associated with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease known to occur in genetically susceptible individuals after exposure to certain unknown environmental factors. HLA-DR3-DQ2 or DR4-DQ8 are established genetic markers for the disease. MHC class I chain-related gene-A (MICA) gene polymorphism has been proposed to be associated with T1DM. To identify the environmental factors and for implementing intervention trials to prevent T1DM, it is important to screen subjects at genetically increased risk for developing T1DM. The All Babies in Southeast Sweden (ABIS) study aims to assess the risk of future progression to T1DM in the general child population. In the present report, we studied the frequency of MICA alleles among newborn babies carrying high-risk HLA DQ2 or DQ8. Of 2821 newborns, we found 563 subjects positive for DQ2, 583 subjects positive for DQ8, 133 subjects positive for DQ2-DQ8 (heterozygous), and 1013 subjects positive for either DQ2 or DQ8. Of these 1013 babies, we typed 499 babies for MICA. Frequency of MICA5 was 38% among DQ8+, 35% among for DQ2-DQ8 (heterozygous) positives, and 22.5% among DQ2+ babies. Frequency of MICA5.1 was 81% among DQ+, 62% among DQ8+, and 71% among DQ2-DQ8 (heterozygous) positives. Frequency of MICA6 was between 20% and 22% among the three groups. Frequency of MICA5/5.1 was 19% among DQ2-DQ8 (heterozygous) positives and between 12% and 13% among those positive for DQ2, DQ8, DQ2, or DQ8. The results from genetic typing in this study would be useful, in conjunction with results from autoantibody analysis that are prospectively being followed-up in all the babies, to develop an approach for identifying children at risk for developing T1DM. Inclusion of MICA typing in addition to HLA could be useful for screening of genetic markers associated with T1DM.

Alleles↗

Modulation of antiepileptic effect of phenytoin and carbamazepine by melatonin in mice.

The pharmacokinetic and pharmacodynamic interaction of phenytoin and carbamazepine with melatonin was studied in a maximal electroshock seizure (MES) model in mice. The anticonvulsant ED(20), ED(33), ED(50) and ED(100) of phenytoin and carbamazepine, and ED(50) of melatonin were determined. Thereafter, the subanticonvulsant doses of phenytoin and carbamazepine were combined with ED(50) dose of melatonin. In combination with melatonin, 100% protection against seizures was achieved with phenytoin and carbamazepine in doses as low as ED(50) and ED(33), respectively. Serum levels of phenytoin and carbamazepine in animals that received ED(50) dose of phenytoin and carbamazepine per se, were not significantly different to those of the groups that received melatonin also. The study suggests that the synergistic antiepileptic effect is most likely a pharmacodynamic interaction, and not due to pharmacokinetic changes. Melatonin, thus, can be a potential adjunct to antiepileptic drugs, achieving a therapeutic effect at lower concentrations, hence limiting their dose-related toxicities.

Animals↗

Cutaneous reactions in patients with solitary cysticercus granuloma on phenytoin sodium.

Several medical conditions are believed to be associated with an increased risk of cutaneous adverse reactions to anti-epileptic drugs. The aim of this study was to study the frequency and nature of cutaneous reactions in a cohort of patients being treated with phenytoin sodium for seizures, who were divided into those with a solitary cysticercus granuloma (SCG) and those with a condition other than SCG, to determine if the presence of SCG increases the risk of cutaneous adverse reaction to phenytoin. A cohort of 117, consecutively begun on treatment with phenytoin for seizure control, were followed up prospectively for the development of cutaneous reactions. There were 63 patients with SCG upon imaging and 54 patients to whom phenytoin was administered for seizures due to causes other than SCG or multiple neurocysticercosis. Cutaneous reactions were significantly more common (p = 0.02) in patients with SCG (9/63 patients; 14.3%) than in controls (2/54 patients; 3.7%). The spectrum of skin reactions in patients with SCG included benign skin rash (n = 3), anticonvulsant hypersensitivity syndrome (n = 4), Stevens-Johnson syndrome (n = 1), and urticaria (n = 1). Individuals with seizures due to SCG have a high incidence of cutaneous adverse reactions to phenytoin. This fact should be kept in mind when initiating them on treatment with this anti-epileptic drug.

Adult↗

Inhibition of skin sphingosine synthesis: enhanced percutaneous permeation of 5-fluorouracil.

The present study was designed to investigate the role of skin sphingosine inhibition in enhancing the transcutaneous permeation of 5-fluorouracil (5-FU), a hydrophilic drug, across rat skin. Ethanol-perturbation significantly reduced the sphingosine content as compared to that in normal skin until 24 h of perturbation (p < 0.05). To maintain the low content of sphingosine for a longer time, beta-chloroalanine (beta-CA), a selective inhibitor of serine palmitoyl transferase, was used for inhibiting the sphingosine synthesis in viable skin. Application of beta-CA (600 microg or 1200 microg/7 cm2) to viable skin perturbed with ethanol significantly reduced the sphingosine content until 48 h as compared to that in perturbed viable skin (p < 0.05). However, the sphingosine content in viable skin perturbed with ethanol and treated with lower doses (200 or 400 microg/7 cm2) of beta-CA, returned significantly close to that in ethanol-perturbed viable skin at 36 h (p < 0.05). Skin sphingosine synthesis inhibition efficacy of 1200 microg beta-CA was insignificantly different to that of 600 microg dose of beta-CA at 36 h or 48 h (p < 0.05). The systemic delivery of percutaneously applied 5-FU across ethanol-perturbed rat skin treated with either 600 microg or 1200 microg beta-CA was significantly greater as compared to that obtained after oral administration or after application of lower percutaneous doses of beta-CA (p < 0.05). Higher Cmax, MRT, AUC and maintenance of effective plasma concentration of 5-FU for 46 h was achieved by a single topical application of a formulation containing 5-FU and 600 microg beta-CA to ethanol-perturbed skin.

Administration, Oral↗

Changing trends in the hospital management of unstable angina: a drug utilization analysis.

OBJECTIVE: The current study was designed to investigate drug utilization in the management of unstable angina in India and to examine the changing trends in the management of unstable angina over the past 4 years. METHODS: We conducted a prescription survey to examine the use of antianginal drugs in patients with unstable angina in a tertiary care Indian hospital. The use of concurrent medications such as antidiabetic, antihypertensive and lipid-lowering agents was also examined. This study results were compared with a similar study done in this institute 4 years earlier. RESULTS: A total of 159 consecutive prescriptions were evaluated. Aspirin (86%), nitroglycerin infusion (77%) and low-molecular weight heparins (93%) were the most frequently prescribed drugs. Enoxaparin accounted for 76% of the total LMWH use. One of the heparins was used by 92% of all patients, angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers by 70% and 67%, respectively. Lipid-lowering agents (57%), antidiabetic agents (16%) and antianxiety agents (33%), in addition to antianginals, were also frequently co-administered. Time trend analysis showed that the use of unfractionated heparin fell from 35% to 10% and the use of ACEIs and enoxaparin increased from 17% to 70% and from 51% to 71%, respectively. CONCLUSIONS: The study showed that unfractionated heparin is less frequently used in the treatment of unstable angina than in the past and that ACEIs are preferred to calcium channel blockers. Enoxaparin remains the most commonly used low-molecular weight heparin for this indication. A variety of low-molecular weight heparins are available for therapy but comparative clinical trials of efficacy and pharmacoeconomic studies comparing the various LMWHs still need to be carried out.

Angina, Unstable↗

Early postnatal behavior deficits after maternal carbon dioxide pneumoperitoneum during pregnancy.

BACKGROUND: In this study, we tested the hypothesis that maternal pneumoperitoneum produces early postnatal behavior deficits in the offspring. METHODS: Time-dated pregnant guinea pigs were exposed to 45 min of carbon dioxide (CO2) pneumoperitoneum at a pressure of 7 mmHg. There was no manipulation of the control animals. On postnatal days (PND) 10 and 20, the behavior of their offspring was assessed by monitoring the locomotor activity of each of the pups in a 1 x 1 m chamber demarcated into 100 squares. Locomotor data was log-transformed and expressed as mean values (SD). RESULTS: At PND 10, pneumoperitoneum offspring exhibited significantly higher levels of locomotor activity than the offspring of controls (1.81 +/- 0.48 vs 1.33 +/- 0.78). The pneumoperitoneum pups continued to exhibit hyperactive behavior at PND 20 (1.83 +/- 0.72 vs 1.20 +/- 0.72). CONCLUSIONS: Maternal pneumoperitoneum produces postnatal hyperactivity in guinea pig offspring, suggesting that there may be long-term consequences associated with the physiologic changes produced in the fetus during CO2 insufflation.

Animals↗