Biomedical subjects

A K Srivastava

Publications and source records attributed to A K Srivastava.

At least 19 recordsLinked to original sources

PubMed2007

Pharmacokinetic profile of erythromycin after intramammary administration in lactating dairy cows with specific mastitis.

The pharmacokinetics of erythromycin was studied in five lactating dairy cows following single intramammary infusion of 300 mg erythromycin in each of two quarters per cow with specific mastitis. Levels of erythromycin in plasma and quarter milk samples were measured by agar plate diffusion assay using Micrococcus luteus (ATCC 9341) as the test organism. Erythromycin level in plasma reached a peak concentration value (C(max)) of 0.07 +/- 0.01 microg/ml at 30 min; thereafter, levels declined gradually to reach 0.05 +/- 0.00 microg/ml 12 h post drug administration. The pharmacokinetic profile of the drug revealed mean absorption half life (t(1/2 ka)) as 0.26 +/- 0.05 h. The drug was eliminated slowly with elimination half-life (t(1/2 beta)) of 13.75 +/- 0.35 h and elimination rate constant (k(el)) of 0.04 +/- 0.00 h(-1). The volume of distribution based on the zero-time plasma concentration intercept of the least-squares regression line of the elimination phase (V(d(B))) was 0.032 L/kg. The drug crossed to untreated quarters also; mean drug levels of 0.20 +/- 0.07, 0.23 +/- 0.07, 0.17 +/- 0.04, and 0.17 +/- 0.04 microg/ml were found at 3, 6, 8 and 12 h, respectively. The mean drug concentration for treated quarters was measured as 22.97 +/- 2.31 microg/ml milk at first milking (12 h) following drug infusion. No apparent adverse reaction was seen in cows administered erythromycin. It is concluded that following intramammary infusion erythromycin diffuses readily and extensively in various body fluids and tissues and adequate concentration is maintained in udder tissues for at least 12 h post intramammary administration. Thus, erythromycin may be recommended for local therapy of acute mastitis caused by Gram-positive bacteria in lactating dairy cows.

Animals↗

PubMed2006

Antihyperglycemic and antidyslipidemic agent from Aegle marmelos.

The plant Aegle marmelos belongs to the family of Rutaceae. From the leaves of A. marmelos an alkaloidal-amide, Aegeline 2, was isolated and found to have antihyperglycemic activity as evidenced by lowering the blood glucose levels by 12.9% and 16.9% at 5 and 24h, respectively, in sucrose challenged streptozotocin induced diabetic rats (STZ-S) model at the dose of 100mg/kg body weight. Aegeline 2 has also significantly decreased the plasma triglyceride (Tg) levels by 55% (P<0.001), total cholesterol (TC) by 24% (P<0.05), and free fatty acids (FFA) by 24%, accompanied with increase in HDL-C by 28% and HDL-C/TC ratio by 66% in dyslipidemic hamster model at the dose of 50mg/kg body weight. The reasonable mapping of compound 2 to validated pharmacophoric hypothesis and 3D QSAR model with an estimated activity (283nM) suggest that the compound 2 might be a beta(3)-AR agonist.

Adrenergic beta-3 Receptor Agonists↗

PubMed2006

Diastereoselective synthesis of glycosylated prolines as alpha-glucosidase inhibitors and organocatalyst in asymmetric aldol reaction.

1,3-Dipolar cycloaddition of azomethine ylides and glycosyl E-olefins in presence of LDA led to diastereoselective formation of C-glycosylated proline esters. The selected esters on regioselective hydrolysis with LiOH gave C-glycosyl prolines. Few of the proline esters exhibited very good alpha-glucosidase inhibitory activity. The organocatalytic activity of the proline derivatives in a prototype Aldol reaction has also been investigated.

Aldehydes↗

PubMed2006

Identification of lead-regulated genes by suppression subtractive hybridization in the heavy metal accumulator Sesbania drummondii.

Heavy metal contamination of soils is of widespread occurrence as a result of human, agricultural and industrial activities. Among heavy metals, lead is a potential pollutant that readily accumulates in soils and sediments. Although lead is not an essential element for plants, it gets easily absorbed and accumulated in Sesbania drummondii, which exhibits a significant level of tolerance to lead. The response of a metal tolerant plant to heavy metal stress involves a number of biochemical and physiological pathways. To investigate the overall molecular response of a metal-tolerant plant to lead exposure, suppression subtractive hybridization (SSH) was used to construct a cDNA library enriched in lead induced mRNA transcripts from lead-tolerant Sesbania. Screening the library by reverse Northern analysis revealed that between 20 and 25% of clones selected from the library were differentially regulated in lead treated plants. After differential screening, we isolated several differentially expressed cDNA clones, including a type 2 metallothionein (MT) gene which is involved in detoxification and homeostasis and shown to be differentially regulated in lead treated plants. The data from the reverse Northern analysis was further confirmed with conventional Northern analysis of a select group of genes including MT, ACC synthase/oxidase, cold-, water stress-, and other abiotic stress-induced genes, which are up-regulated rapidly in response to lead treatment. The mRNA levels of MT increased substantially after lead treatment indicating a potential role for it under lead stress in Sesbania. The present results show that SSH can serve as an effective tool for isolating genes induced in response to lead heavy metal tolerance in Sesbania. A better understanding of lead induced gene expression in Sesbania should help select candidates associated with remediation of heavy metal toxicity. The possible link between this result and the heavy-metal response of plants is discussed.

Amino Acid Sequence↗

PubMed2006

A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family.

PURPOSE: A five-generation Hispanic pedigree with autosomal dominant zonular pulverulent cataract was studied to identify the causative mutation in connexin 46 (Cx46), a gap junction protein responsible for maintaining lens homeostasis. METHODS: Twenty-six individuals from the family were comprehensively clinically examined. DNA was extracted from their peripheral blood samples. The DNA was used for automated genotyping with fluorescently labeled microsatellite markers and for mutation detection by automated sequencing. RESULTS: A novel D3Y missense mutation in GJA3 segregated with autosomal dominant (AD) zonular pulverulent cataract throughout the family. The mutation was absent in the unaffected individuals in the family and in 230 control chromosomes. CONCLUSIONS: A novel mutation causing AD zonular pulverulent cataract has been identified in a Hispanic Central American family. This is the first report of a mutation in GJA3 causing autosomal dominant congenital cataract (ADCC) in this ethnic group. It is also the first reported cataract-causing mutation in the NH2-terminal region of the Cx46 protein.

Aspartic Acid↗

PubMed2006

Novel substituted naphthalen-1-yl-methanone derivatives as anti-hyperglycemic agents.

A series of aminoalkoxy phenyl-substituted naphthalene-1-yl-methanone was synthesized and tested for its anti-hyperglycemic activity in SLM and STZ-S rat models. Some compounds (3b, 4c and 4h) of the series were showing significant anti-hyperglycemic activity in male Sprague-Dawley rats in sucrose-loaded model (SLM) as well as in streptozotocin-induced model (STZ-S). Active compounds were also evaluated for relative binding affinity against glucagon receptor.

Animals↗

PubMed2006

Dynamics of polymorphic nanostructures: from growth to collapse.

The deposition of preformed clusters on surfaces offers new possibilities to build complex artificial nanostructures, the shape of which depends on the cluster size. We describe routes for generating unusual polymorphic nanoislands, which constitute unique platforms for exploring instabilities. As coverage increases, the constraints accumulated in such nanostructures induce spectacular flattening collapse processes, which are not observed when the constraints are imposed by the substrate.

Computer Simulation↗

PubMed2006

Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies.

We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.

Abnormalities, Multiple↗

PubMed2005

Effect of surfactants on the dissociation constants of ascorbic and maleic acids.

The dissociation equilibria of ascorbic and maleic acids have been studied in certain cationic, anionic and non-ionic micellar media and their pK(a) values have been evaluated by the potentiometric, conductometric and spectrophotometric techniques. These pK(a) values have been found to shift in micellar media as compared to those in pure water. The differences in the values have been attributed to the solvent properties of the interfacial and bulk phases involving contribution from the micellar surface potential in the case of charged micelles. The values of the limiting molar conductance of the acids have been determined in the various surfactants and were found to be different in different surfactants. In case of the cationic surfactants the limiting molar conductance was found to increase with increase in surfactant concentration.

Anions↗

PubMed2005

Biaryls and heterobiaryls as alpha-glucosidase and protein tyrosine phosphatase inhibitors.

Various 6-aryl-4-substituted-2H-pyran-2-one-3-carbonitriles (1a-d) have been synthesized as precursor for the synthesis of 3,4-dihydro-1H-isothiochroman (2a) and benzocycloalkanes (2b-e). Highly functionalized 9-thiaphenanthrene (3b) and phenanthrene (3a) have also been obtained from the reaction of 1c with thiochroman-4-one and 1-tetralone separately. Similarly 4 has been obtained by the ring transformation of 1d by 4-trifluoromethylacetophenone. Most of the synthesized compounds were evaluated for alpha-glucosidase and protein tyrosine phosphatase inhibitory activities. Some of the compounds, 2a, 3a and b and 4 displayed better alpha-glucosidase inhibitory activity compared to standard drug acarbose.

Enzyme Inhibitors↗

PubMed2005

Evidence of a common founder for SCA12 in the Indian population.

Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' region of the PPP2R2B gene on chromosome 5q31-5q32. We found that it accounts for approximately 16% (20/124) of all the autosomal dominant ataxia cases diagnosed in AIIMS, a major tertiary referral centre in North India. The length of the expanded allele in this population ranges from 51-69 CAG triplets. Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning approximately 137 kb downstream of CAG repeat in the PPP2R2B gene. Analysis of 20 Indian SCA12 families and ethnically matched normal unrelated individuals revealed one haplotype to be significantly associated with the affected alleles (P= 0.000), clearly indicating the presence of a common founder for SCA12 in the Indian population. This haplotype was not shared by the American pedigree with SCA12. Therefore, the SCA12 expansion appears to have originated at least twice.

Alleles↗

PubMed2005

Oral sustained delivery of atenolol from floating matrix tablets-formulation and in vitro evaluation.

Floating matrix tablets of atenolol were developed to prolong gastric residence time and increase drug bioavailability. Atenolol was chosen as a model drug because it is poorly absorbed from the lower gastrointestinal tract. The tablets were prepared by direct compression technique, using polymers such as hydroxypropyl methylcellulose (HPMC K15M, K4M), guargum (GG), and sodium carboxymethylcellulose (SCMC), alone or in combination, and other standard excipients. Tablets were evaluated for physical characteristics viz. hardness, swelling index, floating capacity, thickness, and weight variation. Further, tablets were evaluated for in vitro release characteristics for 8 hr. The effect of effervescent on buoyancy and drug release pattern was also studied. In vitro release mechanism was evaluated by linear regression analysis. GG- and SCMC-based matrix tablets showed significantly greater swelling indices compared with other batches. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium.

Administration, Oral↗

PubMed2005

Insulino-mimetic and anti-diabetic effects of vanadium compounds.

Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes.

Animals↗

PubMed2005

X-ray powder diffraction patterns for certain beta-lactam, tetracycline and macrolide antibiotic drugs.

X-ray powder diffraction (XRD) data for eight beta-lactam viz., ampicillin sodium, ampicillin trihydrate, penicillin G procaine, benzathine penicillin, benzyl penicillin sodium, cefalexin, cefotaxime sodium and ceftriaxone sodium; three tetracyclines viz., doxycycline hydrochloride, oxytetracycline dihydrate and tetracycline hydrochloride; and two macrolide viz., azithromycin and erythromycin estolate antibiotic drugs were obtained using a powder diffractometer. The drugs were scanned from Bragg angles (2theta) of 10 degrees to 70 degrees. The obtained data were tabulated in terms of the lattice spacing (A) and relative line intensities (I/I(I)). This new information may be useful for identifying these drugs from confiscated materials, which has been frequently encountered in forensic laboratories.

Anti-Bacterial Agents↗

PubMed2005

Alteration of pharmacokinetics of oxytetracycline following oral administration of Piper longum in hens.

The pharmacokinetic profile of orally administered oxytetracycline (10 mg/kg body weight) was studied 7 days post oral treatment of Piper longum (15 mg equivalent/kg) in White Leghorn hens (2-2.8 kg). On the day 8, oxytetracycline (OTC) was administered orally and blood samples were collected from the wing vein in heparinised vials for plasma separation at 0 (pre-treatment), 15, 30, 60, 120, 240, 360, 480 and 600 minutes post OTC administration. Plasma OTC concentrations were determined by microbial assay technique using Bacillus cereus var. mycoides (ATCC 11778) as test organism. The plasma levels of OTC against time were adequately described by one compartment open model. The pharmacokinetic data revealed that P.longum treated animals had significantly higher area under curve (AUC), area under the first moment of plasma drug concentration-time curve (AUMC) and mean residential time (MRT). Prior treatment of P.longum significantly reduced elimination rate constant(beta)and increased elimination half life (t(1/2beta)). The total body clearance (Cl(B)) reduced by 21%whereas total duration of pharmacological effect (t(d)) increased by 29%. The treatment with P. longum reduced loading and maintenance dose by 33.3 and 39%, respectively.

Administration, Oral↗

PubMed2004

Biotechnological aspects of the production of the anticancer drug podophyllotoxin.

The natural lignan podophyllotoxin, a dimerized product of two phenylpropanoid moieties which occurs in a few plant species, is a pharmacologically important compound for its anticancer activities. It is used as a precursor for the chemical synthesis of the anticancer drugs etoposide, teniposide and etopophose. The availability of this lignan is becoming increasingly limited because of the scarce occurrence of its natural sources and also because synthetic approaches for its production are still commercially unacceptable. Biotechnological production using cell culture may be considered as an alternative source. Selection of the best performing cell line, its maintenance and stabilization are necessary prerequisites for its production in bioreactors and subsequent scale-up of the cultivation process to the industrial level. Scale-up of growth and product yield depends on a multitude of factors, such as growth medium, physicochemical conditions, seed inoculum, type of reactor and processing conditions. The composition of the growth medium, elicitors and precursors, etc. can markedly influence the production. Optimum levels of parameters that facilitate high growth and product response in cell suspensions of Podophyllum hexandrum have already been determined by statistical design. P. hexandrum cells have successfully been cultivated in a 3-l stirred-tank bioreactor under low shear conditions in batch and fed-batch modes of operation. The batch kinetic data were used to identify the mathematical model which was then used to develop nutrient-feeding strategies for fed-batch cultivation to prolong the productive log phase of cultivation. An improvement in the production of podophyllotoxin to 48.8 mg l(-1) in a cell culture of P. hexandrum was achieved, with a corresponding volumetric productivity of 0.80 mg l(-1) day(-1), when the reactor was operated in continuous cell-retention mode. Efforts are being made to further enhance its production levels by the development of hairy root culture or by varying the channeling of precursors towards the desired biosynthetic pathway by molecular approaches.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Synthesis and antihyperglycemic activity of chalcone based aryloxypropanolamines.

A series of aryloxypropanolamines (5a-r) of different chalcones (3a-e) were synthesized and evaluated for antihyperglycemic activity in sucrose loaded (SLM) and streptozotocin (STZ) induced diabetic animal models. Among them compounds 5a, g, m, o, p and r showed significant reduction in blood glucose levels in both SLM and STZ animal models.

Animals↗

PubMed2004

Mapping quantitative trait loci that influence blood levels of alkaline phosphatase in MRL/MpJ and SJL/J mice.

To examine the hypothesis that serum alkaline phosphatase (ALP) levels have a heritable component, we analyzed blood from two inbred strains of mice, MRL/MpJ and SJL, which exhibit 90% difference in total serum ALP activity (268+/-26 vs. 140+/-15 U/l, respectively, P<0.001). A genome-wide scan was carried out using 137 polymorphic markers in 518 F2 female mice. Serum ALP activity in the F2 progeny showed a normal distribution with an estimated heritability of 56%. Genome-wide scan for cosegregation of genetic marker data with serum ALP activity revealed three major quantitative trait loci (QTL), one each on chromosomes 2 (LOD score 3.8), chromosome 6 (LOD score 12.0), and chromosome 14 (LOD score 3.7). In addition, there was one suggestive QTL on chromosome 2 (LOD score of 3.3). In aggregate, these QTLs explain 22.5% of variance in serum ALP between these two strains. Serum ALP showed a moderate but significant correlation with body weight adjusted total body bone mineral density (r=0.12, P=0.0108) and periosteal circumference at midshaft tibia (r=0.15, P=0.0006) in F2 mice. The chromosome 6 locus harboring the major serum ALP QTL also contains a major BMD and bone size QTL, identified earlier, between these two strains of mice; in addition, this QTL is also close to the locus that regulates IGF-I levels (LOD score 8-9) in C3HB6 F2 mice. These common QTLs indicate that the observed difference in ALP and BMD or bone size may be regulated by same loci (or genes). Accordingly, the osteoblast cells isolated from femur and tibia of MRL mice showed a significantly higher number of ALP +ve cells/colony and two- to threefold higher ALP activity (P<0.001) as compared to the cells isolated from SJL mice, thus suggesting that differences in serum ALP between MRL and SJL reflect difference in ALP expression from osteoblasts from these strains of mice. These data suggest that serum ALP levels are genetically determined and correlate with cellular mechanisms that differentiate BMD accrual in these two strains of mice. The findings that ALP and BMD traits share the same loci on chromosome 6 suggest a role for genetic determinants of bone formation in overall BMD accretion.

Alkaline Phosphatase↗