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A Naidu

Publications and source records attributed to A Naidu.

At least 19 recordsLinked to original sources
PubMed2006

Isolation, structural elucidation and characterization of impurities in Cefdinir.

Three unknown impurities in Cefdinir bulk drug at levels below 0.2% (ranging from 0.05 to 0.2%) have been detected by high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of Cefdinir using preparative HPLC. Based on the spectral data (NMR, IR and MS) the structures of these impurities were characterized as (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid-5-oxide (I). (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-8-oxo-3-vinyl-5-thia-1-azabi-cyclo [4.2.0] oct-3-ene-2-carboxylic acid (II). (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-8-oxo-3-methyl-5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid (III), respectively. The origin and structural elucidation of all impurities have been discussed.

Anti-Bacterial Agents↗
PubMed2006

Structural identification and characterization of impurities in ceftizoxime sodium.

Ceftizoxime sodium is a parenteral beta-lactamic antibacterial drug. In the synthesis of ceftizoxime sodium, eight process related impurities were detected in HPLC analysis. Pure impurities obtained by both synthesis and preparative HPLC were co-injected with ceftizoxime sample to confirm the retention times in HPLC. The impurities were characterized as, (6R,7R)-7-amino-3-cephem-4-carboxylic acid (impurity I); (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-cephem-1-oxo-4-carboxylic acid (impurity II); (4RS,6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino) acetamido]-3,4-dihydro-3-cephem-4-carboxylic acid (impurity III); (6R,7R)-7-[(E)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-cephem-4-carboxylic acid (impurity IV); (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-cephem-N-(3-cephem-4-carboxy-7-yl)-4-carboxamide (impurity V); (6R,7R)-7-[(Z)-2-[[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetylamino]thiazol-4-yl]-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (impurity VI); 2-mercaptobenzothiazole (impurity VII) and 2-mercapto benzothiazolyl [(Z)-2-(2-amino-4-thiazolyl)-2-methoxyimino] acetate (impurity VIII). Structural elucidation of all impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) has been discussed.

Anti-Bacterial Agents↗
PubMed2003

Effect of oxygen on breath markers of oxidative stress.

Supplemental oxygen is often administered to induce hyperoxia in nonhypoxic patients for indications such as chest pain, despite lack of evidence of clinical benefit. Induced hyperoxia is potentially toxic, since it may increase oxidative stress and peroxidative damage to deoxyribonucleic acid, lipids and proteins. The aim of this study was to establish whether supplemental oxygen induces oxidative stress in nonhypoxic subjects. Breath markers of oxidative stress were measured in 31 healthy subjects before and after breathing 28% oxygen at 2.0 L x min(-1) via nasal prongs for 30 min while resting. The criterion standard of oxidative stress was the breath methylated alkane contour (BMAC), a three-dimensional plot of the alveolar gradients of C4-C20 alkanes and monomethylated alkanes produced by lipid peroxidation. Volatile organic compounds (VOCs) in breath were assayed by gas chromatography and mass spectroscopy, and the BMACs before and after oxygenation were compared. Following oxygenation, there was a significant increase in mean volume under the curve of the BMAC and in alveolar gradients of three VOCs: 3-methyltridecane, 3-methylundecane and 5-methylnonane. Breath markers of oxidative stress were significantly increased in normal volunteers breathing supplemental oxygen for 30 min.

Adult↗
PubMed2001

Conversion of brain apolipoprotein E to an insoluble form in a mouse model of Alzheimer disease.

A beta deposition in the APPV717F transgenic model of Alzheimer's pathology involves apolipoprotein E (apoE). We measured soluble and insoluble apoE in brain region extracts at an early and late stage of plaque development. The apoE levels in the insoluble fraction were greatly elevated in the hippocampus and cortex of aged transgenic animals but were unchanged in wild type or young APPV717F animals. Soluble apoE levels were unaltered. A beta levels were also measured and a positive correlation between apoE and A beta in the insoluble fraction was observed. ApoE transcription was increased approximately 3-fold in the hippocampus of 17-month-old APPV717F mice, suggesting a region-specific upregulation of apoE transcription in the brains of APPV717F mice to compensate for apoE sequestered with fibrillar A beta.

Alleles↗
PubMed2000

Behavioral disturbances without amyloid deposits in mice overexpressing human amyloid precursor protein with Flemish (A692G) or Dutch (E693Q) mutation.

The contribution of mutations in the amyloid precursor protein (APP) gene known as Flemish (APP/A692G) and Dutch (APP/E693Q) to the pathogenesis of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis of the Dutch type, respectively, was studied in transgenic mice that overexpress the mutant APP in brain. These transgenic mice showed the same early behavioral disturbances and defects and increased premature death as the APP/London (APP V717I), APP/Swedish (K670N, M671L), and other APP transgenic mice described previously. Pathological changes included intense glial reaction, extensive microspongiosis in the white matter, and apoptotic neurons in select areas of the brain, while amyloid deposits were absent, even in mice over 18 months of age. This contrasts with extensive amyloid deposition in APP/London transgenic mice and less pronounced amyloid deposition in APP/Swedish transgenic mice generated identically. It demonstrated, however, that the behavioral deficiencies and the pathological changes in brain resulting from an impaired neuronal function are caused directly by APP or its proteolytic derivative(s). These accelerate or impinge on the normal process of aging and amyloid deposits per se are not essential for this phenotype.

Aggression↗
PubMed2000

Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress.

Reactive oxygen species (ROS) are toxic byproducts of mitochondrial energy production that inflict oxidative stress, a constant barrage of damage to DNA, proteins, lipids, and other biologically important molecules. Oxidative stress has been implicated as a pathologic mechanism in aging and in several diseases. We developed a display of apparent new markers of oxidative stress in human beings, the breath methylated alkane contour (BMAC). The BMAC is a three-dimensional display of C4 to C20 alkanes and monomethylated alkanes in breath, with x-axis = carbon chain length, z-axis = methylation site, and y-axis = alveolar gradient (relative abundance in breath minus relative abundance in room air). In 102 normal human subjects of 9 to 89 years of age, alveolar gradients of components of the BMAC increased significantly with age. The mean alveolar gradient of all components of the BMAC varied from negative in the youngest quartile (ages 9 to 31 years) to positive in the oldest quartile (ages 74 to 89 years)(P < 2.10(-9)). These findings were consistent with an increase in oxidative stress with advancing age, although an age-related decline in clearance by cytochrome p450 may have contributed. The BMAC provides a display of apparent new markers of oxidative stress with potential applications in aging research, clinical diagnosis, pharmacology, and toxicology.

Adolescent↗
PubMed1999

Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain.

Transgenic mice overexpressing different forms of amyloid precursor protein (APP), i.e. wild type or clinical mutants, displayed an essentially comparable early phenotype in terms of behavior, differential glutamatergic responses, deficits in maintenance of long term potentiation, and premature death. The cognitive impairment, demonstrated in F1 hybrids of the different APP transgenic lines, was significantly different from nontransgenic littermates as early as 3 months of age. Biochemical analysis of secreted and membrane-bound APP, C-terminal "stubs," and Abeta(40) and Abeta(42) peptides in brain indicated that no single intermediate can be responsible for the complex of phenotypic dysfunctions. As expected, the Abeta(42) levels were most prominent in APP/London transgenic mice and correlated directly with the formation of amyloid plaques in older mice of this line. Plaques were associated with immunoreactivity for hyperphosphorylated tau, eventually signaling some form of tau pathology. In conclusion, the different APP transgenic mouse lines studied display cognitive deficits and phenotypic traits early in life that dissociated in time from the formation of amyloid plaques and will be good models for both early and late neuropathological and clinical aspects of Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Risk factors for laparoscopically confirmed pelvic inflammatory disease: findings from Mumbai (Bombay), India.

OBJECTIVES: Sexually transmitted diseases (STDs) are an important cause of pelvic inflammatory disease (PID) but have often not been detected in microbiological studies of Indian women admitted to hospital gynaecology wards or private clinics. In this cross sectional study, women living in the inner city of Mumbai (Bombay) were investigated for socioeconomic, clinical, and microbiological risk factors for PID. METHODS: Microbiological tests and laparoscopic examination were carried out on 2736 women aged < or = 35 years who came to a health facility with suspected acute salpingitis or infertility or for laparoscopic sterilisation. 86 women with a clinical diagnosis of PID were not referred for laparoscopy although their characteristics are described. Associations between various risk factors and PID status were investigated and logistic regression performed on all factors that remained significant. RESULTS: Of women with a laparoscopically confirmed evaluation, 26 women had acute and 48 chronic pelvic infection. Independent risk factors for PID were later age at menarche (> or = 14 years), a history of stillbirth and no previous pregnancy, history of tuberculosis, STD, dilatation and curettage or previous laparoscopy, and presence of Gardnerella vaginalis. CONCLUSIONS: It is concluded that STD related risk factors applied to only a small proportion of PID cases and that other determinants of PID are important, including obstetric complications, invasive surgical procedures such as laparoscopy, and tuberculosis.

Adult↗
PubMed1996

Beta-amyloid peptide secretion by a microglial cell line is induced by beta-amyloid-(25-35) and lipopolysaccharide.

beta-Amyloid protein (betaAP) deposition is a neuropathologic hallmark of Alzheimer's disease (AD). Yet, the source of cerebral betaAP in AD is controversial. We examined the production of betaAP by the BV-2 immortalized microglial cell line using a sensitive enzyme immunoassay. Constitutive production of betaAP was detected in conditioned media from unstimulated BV-2 cells. Further, production of betaAP was induced by treatment of cultures by lipopolysaccharide (LPS) or betaAP-(25-35) and was inhibited by the calpain protease inhibitor MDL 28170. Treatment of BV-2 cells with LPS or betaAP-(25-35) did not affect cell-associated beta-amyloid precursor protein levels. These findings suggest that microglia may be an important source of betaAP in AD, and that microglial production of betaAP may be augmented by proinflammatory stimuli or by betaAP itself.

Alzheimer Disease↗
PubMed1995

Association of surfactant protein C with isolated alveolar type II cells.

Surfactant protein C (SP-C) is a small hydrophobic protein that is synthesized and secreted by alveolar type II cells. The mechanism of clearance of SP-C from the alveolar airspace is not well understood, although previous studies demonstrated that recombinant SP-C instilled into the lungs of spontaneously breathing anaesthetized rats was taken up by type II cells and incorporated into lamellar bodies. The current investigation was undertaken to characterize the interaction of a complex of SP-C and surfactant-like lipids with freshly isolated rat alveolar type II cells under conditions in which the extracellular milieu can be regulated. SP-C was isolated from alveolar proteinosis lavage fluid and radiolabeled with 125I-Bolton-Hunter reagent. The radiolabeled protein retained its ability to facilitate adsorption of phospholipids to an air/liquid interface. Labeled human SP-C associated with isolated type II cells in a concentration-dependent manner that was also dependent upon temperature and time. The association of labeled SP-C with isolated type II cells did not saturate up to 150 micrograms/ml. SP-A significantly enhanced the association of SP-C with isolated type II cells. Under the experimental conditions tested, SP-C was not degraded to TCA-soluble products. These results are consistent with the hypothesis that association or uptake of SP-C by type II cells may be enhanced by SP-A and that like SP-A, SP-C is recycled by type II cells.

Animals↗
PubMed1995

beta-Amyloid peptide produced in vitro is degraded by proteinases released by cultured cells.

The primary histopathological feature of Alzheimer's disease is the accumulation of beta-amyloid in the brains of afflicted individuals. This peptide has been shown to be produced and liberated both in vitro and in vivo by normal physiological processes. The mechanism by which beta-amyloid is formed, as well as that by which it may be cleared, are events likely to impact on the development and progression of this disease. Thus, the fate of beta-amyloid peptides secreted by cultured mammalian cells was investigated. It was found that levels of the soluble peptide are reduced over time due to the activity of multiple types of proteinases including those from the metallo, aspartyl, and thiol classes. Inhibitors to each class of proteinase can only partially block beta-amyloid degradation, but, if used in combination, they can fully prevent its catabolism. The Kunitz serine proteinase inhibitor domain, present on two beta-amyloid precursor protein isoforms, was found to be an effective inhibitor of beta-amyloid peptide degradation. These data indicate that modulations in expression of secreted proteinases and/or beta-amyloid precursor isoforms may influence levels of beta-amyloid.

Amyloid beta-Peptides↗
PubMed1991

Lung surfactant protein SP-C from human, bovine, and canine sources contains palmityl cysteine thioester linkages.

Lung surfactant is a complex mixture of lipids and proteins that coats the alveoli to reduce surface tension and prevent airspace collapse. One of the principal protein constituents, surfactant protein C (SP-C), has been characterized following isolation from human, canine, and bovine sources. In each species, this highly hydrophobic protein is composed of 33-35 amino acids, the differences being due to NH2-terminal heterogeneity. A COOH-terminal leucine is conserved throughout. The cysteines in each species were found by fast atom bombardment mass spectrometry to be present as thioesters of palmitic acid. Acylation of recombinant SP-C with palmityl coenzyme A, followed by characterization before and after release of the acyl group with 1,4-dithiothreitol, provided corroborating evidence for the native structure.

Acylation↗
PubMed1990

Dextrorphan binds to opioid receptors in guinea-pig brain membranes and is an antagonist at opioid receptors in myenteric plexus.

Dextrorphan (+)-tartrate, purified by repeated crystallization to remove all traces of the enantiomer levorphanol, binds to mu, delta, and kappa sites on guinea-pig brain membranes with lower affinities (by a factor of 400-3200) than levorphanol. In the guinea-pig ileum myenteric plexus longitudinal muscle preparation (GPI), dextrorphan, at 100-200 microM, inhibits the electrically stimulated twitch, but this action is not blocked or reversed by naloxone; both (+)- and (-)-naloxone produce similar non-opioid twitch inhibition at comparable concentrations. At 10-20 microM, dextrorphan blocks and reverses the twitch inhibition due to mu and kappa agonists, but the blockade can be overcome only partially by increasing the agonist concentration. We conclude that dextrorphan is an opioid ligand with low affinity and with antagonist effect on opioid receptors in the GPI.

Animals↗
PubMed1989

Multiple opioid receptors: ligand selectivity profiles and binding site signatures.

Methods are described for studying mu, delta, and kappa opioid binding sites, each without interference from the others. A large array of ligands has been characterized by ligand selectivity profiles, graphic depictions of affinities and selectivities. Binding site signatures have been derived, which uniquely describe each of the three types of sites. The mu, delta, and kappa binding sites have interesting common features and distinctive differences.

Animals↗
PubMed1988

"DAKLI": a multipurpose ligand with high affinity and selectivity for dynorphin (kappa opioid) binding sites.

We describe a synthetic ligand, "DAKLI" (Dynorphin A-analogue Kappa LIgand), related to the opioid peptide dynorphin A. A single reactive amino group at the extended carboxyl terminus permits various reporter groups to be attached, such as 125I-labeled Bolton-Hunter reagent, fluorescein isothiocyanate, or biotin. These derivatives have high affinity and selectivity for the dynorphin (kappa opioid) receptor. An incidental finding is that untreated guinea pig brain membranes have saturable avidin binding sites.

Animals↗