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Biomedical subjects

V Arora

Publications and source records attributed to V Arora.

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

Improved postprandial glycemic control during treatment with Humalog Mix25, a novel protamine-based insulin lispro formulation. Humalog Mix25 Study Group.

OBJECTIVE: Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation (NPL) in a ratio of 25:75%. The objective of this study was to compare Humalog Mix25 to human insulin 30/70 (30% regular insulin/70% NPH) with respect to glycemic control. RESEARCH DESIGN AND METHODS: Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month randomized open-label two-period crossover study. Each insulin was administered twice daily, before the morning and evening meals. Information regarding self-monitored blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l), insulin dose, and HbA1c was collected. RESULTS: Treatment with Humalog Mix25 resulted in better postprandial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70. Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments. CONCLUSIONS: In comparison to treatment with human insulin 30/70, twice daily administration of Humalog Mix25 resulted in improved postprandial glycemic control, similar overall glycemic control, and the convenience of dosing immediately before meals.

Blood Glucose↗
PubMed1999

Safety of Ghasa.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed1999

Laparoscopic transabdominal repair of hernia of Morgagni-Larrey.

A patient with symptomatic gall stones was found to have a hernia of Morgagni. The patient complained of upper abdominal symptoms along with heaviness in the chest and mild dyspnea. A complete diagnosis was possible with a chest X ray and a CT scan, which revealed a right-sided Morgagni hernia containing omentum and some bowel loops. It was decided to laparoscopically deal with both lesions at the same sitting. Initially, a laparoscopic cholecystectomy was accomplished. The hernial contents were then reduced and an 8 cm x 5 cm defect was closed with a tailored mesh sutured in place with a hernia stapler. Follow up after one month showed an asymptomatic patient confirmed by CT scan. Morgagni hernia is eminently treatable laparoscopically and must be considered as a first line approach to this problem. It can safely be combined with other laparoscopic procedures.

Cholecystectomy, Laparoscopic↗
PubMed1998

Manipulation of metallothionein expression in the regenerating rat liver using antisense oligonucleotides.

Metallothioneins (MTs) are low molecular weight, zinc-binding proteins that by activating zinc metalloenzymes participate in the regulation of growth and development. The present study was designed to examine the roles of MTs in cell proliferation using an in vivo model of liver regeneration following partial hepatectomy (PH) in rats. The levels of MT-I and MT-II were studied with respect to regulation of proliferative potential, cell cycle checkpoint activity, and oxidative stress in the rat PH model. We synthesized a 17-mer antisense phosphorothioate oligodeoxynucleotide (S-ODN), named aMT, complimentary to the start site of the MT-I mRNA sequence and an appropriate control. Both S-ODNs were administered intraperitoneally at the dose of 5 mg/kg following 70% PH. MT became induced 57.4 +/- 9.8-fold following PH and the said effect became attenuated dramatically following administration of aMT. In addition, PH rats treated with aMT exhibited decreased rate of liver regeneration as measured by expression of proliferating cell nuclear antigen and elevated cell cycle checkpoint activity as determined by expression of p53. The results of these studies suggest that MT isoforms with their high thiol contents do play an important role in cellular functions and especially during stressful states induced by a broad range of mediators generating free radicals.

Animals↗
PubMed1998

Simultaneous intracellular and extracellular pH measurement in the heart by 19F NMR of 6-fluoropyridoxol.

6-Fluoropyridoxol (6-FPOL) was evaluated as a simultaneous indicator of intracellular and extracellular pH and, hence, pH gradient in perfused rat hearts. After infusion, 19F NMR spectra rapidly showed two well-resolved peaks assigned to the intracellular and extracellular compartments, and pH was calculated on the basis of chemical shift with respect to a sodium trifluoroacetate standard. To demonstrate use of this molecule, dynamic changes in myocardial pH were assessed with a time resolution of 2 min during respiratory and metabolic alkalosis or acidosis and ischemia. For a typical heart, intracellular pH (pHi) = 7.14+/-0.01 and extracellular pH (pHe) = 7.52+/-0.02. In response to metabolic alkalosis, pHi remained relatively constant and the pH gradient increased. In contrast, respiratory challenge caused a significant increase in pHi. Independent measurements using pH electrodes and 31P NMR confirmed validity of the 19F NMR results.

Alkalosis, Respiratory↗
PubMed1998

Development of novel 19F NMR pH indicators: synthesis and evaluation of a series of fluorinated vitamin B6 analogues.

We have synthesized a series of novel fluorinated vitamin B6 analogues (6-fluoropyridoxol derivatives) as potential 19F NMR pH indicators for use in vivo. Modifications included addition of aldehyde, carboxyl or aminomethyl groups at the 4- or 5-ring position, and examination of a trifluoromethyl moiety as an internal chemical shift standard. The variation in chemical shift with respect to acid-base titration showed pKa values in the range 7.05-9.5 with a chemical shift sensitivity in the range 7.4-12 ppm. Several of the molecules readily cross cell membranes providing estimates of both intra- and extra-cellular pH in whole blood. 6-Fluoropyridoxamine (6-FPAM) exhibits a pKa = 7.05, which is closer to normal physiological pH than the parent molecule 6-fluoropyridoxol (6-FPOL) (pKa = 8.2), and should thus, be useful for precise and accurate measurements of pH in vivo. Enhanced spectral resolution for 6-FPAM over 6-FPOL is demonstrated in whole blood and the perfused rat heart.

Animals↗
PubMed1998

In vivo properties of an in situ forming gel for parenteral delivery of macromolecular drugs.

PURPOSE: This study characterizes the in vivo properties of an in situ forming gel, comprising of IPC of water-soluble polymers, PMA and PEG, for sustained release of macromolecular drugs. METHODS: 40, 50, or 60% w/v formulations were injected subcutaneously in a rat model either alone, or containing model macromolecules, 3A2-ATG-psODN or REV-psODN, to (i) determine the approximate gelling and residence time of the gel at the site of injection (ii) assess the biological efficacy of the formulation using a MZ sleep time model and (iii) demonstrate specificity of the sequence and selectivity of the psODNs by measuring changes in microsomal enzyme levels and urine volumes. RESULTS: A sol to gel transition requires 15 min in vivo, and the 60% w/v IPC gel remains at the site of injection for up to 72 hr. The MZ sleep times and CYP3A2 expression due to 3A2-ATG-psODNs released from the gel are significantly different compared to that of REV-psODNs. CONCLUSIONS: The IPC solutions exhibit phase transformation in vivo. and demonstrate no evidence of toxicity. The pharmacological effects observed from the of release of 3A2-ATG-psODNs suggest that the formulation can entrap, protect, and sustain the delivery of macromolecules. .

Animals↗
PubMed1998

Two-port laparoscopic cholecystectomy: an innovative new method for gallbladder removal.

Laparoscopic cholecystectomy is the gold standard in gallbladder surgery all over the world today. The operation is routinely performed using four or three ports of entry into the abdomen. We have now modified this procedure and introduced a new innovative two-port method of gallbladder removal. Between September 1997 and November 1997, 50 consecutive patients (41 females and 9 males; mean age 41 years) with calculus cholecystitis underwent our new two-port procedure. In this operation, only the supraumbilical port (10 mm/5 mm) and the epigastric port (10 mm) were used for access. The gallbladder was manipulated through three strategically placed traction sutures, passed through the fundus, the body, and the neck area of the gallbladder, respectively. The operating time required was 35 to 125 minutes, with an average time of 56 minutes. None of the patients required conversion to the four-port technique. All patients were on liquids after 6 hours. The average hospital stay was 1.31 days. Postoperative pain was significantly reduced, and the procedure was cosmetically more acceptable to the patient.

Adult↗
PubMed1998

The third intracellular loop of the rat gonadotropin-releasing hormone receptor couples the receptor to Gs- and G(q/11)-mediated signal transduction pathways: evidence from loop fragment transfection in GGH3 cells.

The GnRH receptor (GnRH-R) belongs to the rhodopsin/beta-adrenergic family of G protein-coupled receptors. The intracellular domains of these receptors, particularly the regions closest to the plasma membrane in intracellular loops 2 (2i) and 3 (3i) as well as some regions located in the membrane-proximal end of the COOH-terminus, are frequently important sites for G protein coupling and specificity determination. Although studies in mouse and human GnRH-R have identified loop 2i as a critical determinant for coupling the receptor to the G(q/11)-mediated signal transduction pathway, given the functional similarity among the members of this particular G protein-coupled receptor subfamily and the fact that the GnRH-R lacks the typical intracellular COOH-terminal domain of its superfamily (a potential site for G protein coupling), we investigated the possibility that loop 3i of this receptor also participates in GnRH-R coupling to G proteins. GGH(3)1' cells, a pituitary-derived cell line that expresses a functional rat GnRH-R coupled to both Gs and G(q/11) proteins, were transiently transfected with a plasmid DNA containing a complementary DNA (cDNA) coding for the entire loop 3i of the GnRH-R as well as with other expression plasmids containing cDNAs encoding loop 3i of other Gs-, G(i/o)-, or G(q/11)-coupled receptors. The effects of coexpression of these loops with the wild-type GnRH-R on inositol phosphate (IP) production, cAMP accumulation, and PRL release were then examined. Transfection of GGH(3)1' cells with the cDNA for loop 3i of the rat GnRH-R (efficiency, 35-45%) maximally inhibited buserelin-stimulated IP turnover by 20% as well as cAMP accumulation and PRL secretion by 30%. This attenuation in cellular responses to a GnRH agonist was statistically significant (P < 0.05) compared with the responses exhibited by GGH(3)1' cells transfected with a control plasmid and stimulated with the same GnRH agonist. Transfection of minigenes coding for loop 3i of the M1Ach-muscarinic and the alpha1B-adrenergic (G(q/11)-coupled) receptors resulted in 25-55% inhibition of maximal GnRH-evoked IP turnover. Paradoxically, loop 3i from the M1Ach-muscarinic receptor also maximally inhibited GnRH agonist-stimulated cAMP accumulation and PRL release by 40% (both effects mediated through activation of the Gs protein). Transfection of loop 3i from the D1A -dopamine receptor (coupled to the Gs protein) produced a selective attenuation (40%) in Gs-mediated cellular responses. In contrast, receptor/G protein coupling appeared unaffected by expression of loop 3i domains derived from two receptors coupled to G(i/o) proteins (M2Ach-muscarinic and alpha2A-adrenergic receptors). These data indicate that the third intracellular loop of the rat GnRH-R is involved in receptor G(q/11) protein coupling and/or selectivity, and in the GGH(3)1' cell line, this loop is also involved in signal transduction mediated through the Gs protein pathway.

Amino Acid Sequence↗
PubMed1996

Biphasic action of cyclic adenosine 3',5'- monophosphate in gonadotropin-releasing hormone (GnRH) analog-stimulated hormone release from GH3 cells stably transfected with GnRH receptor complementary deoxyribonucleic acid.

GH3 cells are a PRL-secreting adenoma cell line derived from pituitary lactotropes. These cells have been stably transfected with rat GnRH receptor complementary DNA to produce four cell lines: GGH(3)1', GGH(3)2', GGH(3)6', and GGH(3)12'. In response to either GnRH or Buserelin (a metabolically stable GnRH agonist), these cell lines synthesize PRL in a cAMP-dependent manner. Only GGH(3)6' cells desensitize in response to persistent treatment with 10(-7) g/ml Buserelin. GGH(3)1', GGH(3)2', and GGH(3)12' cells, however, can be made refractory to Buserelin stimulation by raising cAMP levels either by the addition of (Bu)2cAMP to the medium or by treatment with cholera toxin. In GGH(3) cells, low levels of cAMP fulfill the requirements for a second messenger, whereas higher levels appear to mediate the development of desensitization. The observation that in GGH(3)6' cells, cAMP production persists after the onset of desensitization is consistent with the view that the mechanism responsible for desensitization is distal to the production of cAMP. Moreover, the absence of any significant difference in the amount of cAMP produced per cell in GGH(3)2', GGH(3)6', or GGH(3)12' cells suggests that elevated cAMP production per cell does not explain the development of desensitization in GGH(3)6' cells. We suggest that Buserelin-stimulated PRL synthesis in GGH(3)6' cells is mediated by a different cAMP-dependent protein kinase pool(s) than that in nondesensitizing GGH(3) cells. Such a protein kinase A pool(s) may be more susceptible to degradation via cAMP-mediated mechanisms than the protein kinase pools mediating the Buserelin response in nondesensitizing GGH(3) cells. A similar mechanism has been reported in other systems.

Animals↗
PubMed1996

Free radical scavengers & lipid peroxidation in acute aluminium phosphide poisoning.

Free radicals scavengers superoxide dismuatase (SOD) and catalase and lipid peroxidation were studied in 45 patients of aluminium phosphide poisoning irrespective of age and sex admitted to a hospital in north India during the January 1992 to December 1993. Serial serum superoxide dismutase (SOD), catalase and MDA (malonyldialdehyde) were estimated on days 1, 2 and 5 post-admission depending on the survival of the patients. Serum SOD levels were significantly higher (P < 0.001) but serum catalase was significantly lower (P < 0.001) in patients than controls (patients of peripheral circulatory failure and normals) on days 1 and 2 which suggested stimulation of SOD and inhibition of catalase by phosphine resulting in excessive hydrogen peroxide (H2O2) load. Significantly higher levels of MDA (P < 0.001) in patients than controls on days 1 and 2 indicated enhanced lipid peroxidation in this poisoning. Twenty four patients died constituting a mortality rate of 53.3 per cent. The significantly high levels of SOD and MDA in non-survivors suggested their direct relation to mortality while catalase levels had an inverse relationship. Return of SOD and catalase and MDA to normal or near normal levels in survivors by day 5 suggested abolition of an oxidative stress due to elimination of phosphine.

Acute Disease↗
PubMed1993

Toxicity of exposed aluminium phosphide.

Poisoning by the partially or fully exposed compound of aluminium phosphide (ALP) is becoming common, Fifty patients with history of ingestion of ALP either in the form of broken tablets or granular powder were included in this study for analysis of systemic effects and outcome. Forty patients (Gr. I) consumed broken or granular form of tablets. Ten patients (Gr. II) consumed only powder form of tablets from an old container. 30 patients in group-I developed mild hypotension (BP 80-90 mm Hg). 4 patients (10%) developed ECG changes and mild metabolic acidosis. One patient died constituting 2.5% mortality rate. The patients of group-II neither developed any systemic effects nor showed any mortality. The aim of the study is to differentiate these cases from patients who consume active, fresh compound where mortality rate will be much higher.

Acidosis↗
PubMed1992

Influence of coralline hydroxyapatite used as an ocular implant on the dose distribution of external beam photon radiation therapy.

Coralline hydroxyapatite spheres are used as buried integrated ocular implants after enucleation or evisceration surgery. Because such implants are used after surgery for intraocular malignancy and because some patients may require postoperative radiation therapy for orbital tumor recurrence, the radiation attenuation characteristics of the implant are of interest. The authors evaluated the attenuation and scattering properties of coralline hydroxyapatite implants using a 4 MV photon beam and film dosimetry. Optical density analyses indicate that coralline hydroxyapatite implants have no significant influence on the attenuation or scattering properties of the photon beam. As such, there is no basis for concern that such implants might adversely affect external beam photon irradiation.

Absorptiometry, Photon↗
PubMed1990

Valproate sodium in epilepsy. A clinical trial including monitoring of drug levels.

Sodium valproate was used as monotherapy in 90 cases with epilepsy who had at least one fit per week, irrespective of the type of seizures. The effect of the drug was evaluated on the basis of change in seizure frequency. Serum valproic acid levels were estimated by homogenous enzyme immunoassay. All the patients with absence (5/5) and myoclonic (3/3) seizures and 80% (42/53) of cases with generalized tonic-clonic seizures, became seizure free. Six of ten patients with only tonic seizures became seizure free. An average daily dose of 19.6 mg/kg provided a mean valproic acid level of 81.4 micrograms/ml in all seizure free patients. No correlation could be established between valproate dose and serum levels. Mild transient side effects were noted. No haematologic abnormality or hepatotoxicity was observed. Valproate sodium effectively controlled seizures in a majority of patients with partial seizures. Serum level monitoring helps to establish an optimal dose to keep the patient seizure free. No correlation could be established between side effects and serum levels.

Adolescent↗