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Raj K Gupta

Publications and source records attributed to Raj K Gupta.

At least 19 recordsLinked to original sources
PubMed2006

Novel semi-automated methodology for developing highly predictive QSAR models: application for development of QSAR models for insect repellent amides.

Conventional 3D-QSAR models are built using global minimum conformations or quantum-mechanics based geometry-optimized conformations as bioactive conformers. QSAR models developed using the global minima as bioactive conformers, employing the GFA, PLS and G/PLS methodologies, gave good non-validated r(2) (0.898, 0.868 and 0.922) and performed well on an internal validation test with leave-one-out correlation q(2) (LOO) (0.902, 0.726 and 0.924), leave-10%-out correlation q(2) (L10O) (0.874, 0.728 and 0.883) and leave-20%-out q(2) (L20O) (0.811, 0.716 and 0.907). However, they showed poor predictive ability on an external data set with best predictive r(2) (Pred-r(2)) of 0.349, 0.139 and 0.204 respectively. A novel methodology to mine bioactive conformers, from clusters of conformations with good 3D-spatial representation around pharmacophoric moiety, furnishes highly predictive 3D-QSAR models. The best QSAR model (model A) showed r(2) of 0.989, q(2) (LOO) of 0.989, q(2) (L10O) of 0.980, q(2) (L20O) of 0.963 and Pred-r(2) on eight test compounds of 0.845. The methodology is based on mimicking the multi-way Partial Least Squares (PLS) technique by performing several automated sequential PLS analyses. The poses/shapes of the mined bioactive conformers provide valuable insight into the mechanism of action of the insect repellents. All of the repetitive tasks were automated using Tcl-based Cerius2 scripts.

Algorithms↗
PubMed2005

Cytological findings in a sample of peritoneal aspirate from a case of bile peritonitis.

Bile peritonitis (BP) is a rare and serious condition warranting urgent surgical intervention to prevent the high incidence of mortality. BP is ascribed to the leakage of bile into the peritoneal cavity usually due to a perforation of the gallbladder or common bile duct caused by stones or a trauma. The radiological studies are useful in suggesting the diagnosis. The cytological findings of BP have been reported rarely in the literature characterised by the presence of lakes of stringy bile material admixed with variable numbers of histiocytes, mesothelial cells, and some inflammatory cells. Recently, we have examined an aspirate sample of peritoneal fluid (PF) obtained under ultrasound guidance in a case of BP ascribed to the perforation of the gallbladder in a 19-yr-old female patient in which apart from occasional bile pigment-laden macrophages admixed with a few mesothelial cells and inflammatory cells, numerous crystalline structures of varying shapes, sizes, and colour with birefringence along with some microspheroliths were found. At operation, the abdominal cavity showed a large amount of bile and the gallbladder specimen showed two perforations and gangrenous cholecystitis with numerous yellow-brown somewhat friable stones. The foregoing findings in the aspirate appeared to be of interest because to the best of our knowledge, numerous crystalline structures along with the cytological features of BP have not been described in the English literature.

Adult↗
PubMed2005

Analysis of molecular stereoelectronic similarity between N,N-diethyl-m-toluamide (DEET) analogs and insect juvenile hormone to develop a model pharmacophore for insect repellent activity.

Similarity analysis on molecular stereoelectronic properties of N,N-diethyl-m-toluamide (DEET), natural insect juvenile hormone (JH), a synthetic insect juvenile hormone mimic (JH-mimic, undecen-2-yl carbamate), and DEET compounds reveals remarkable similarities that lead to a reliable pharmacophore for the design of efficacious insect repellents and provide insights for understanding the mechanism of repellent action. The study involves an AM1 quantum chemical computational procedure enabling a conformational search for the lowest and most abundant energy conformers of JH, JH-mimic, and 15 DEET compounds and complete geometry optimization of the conformers. Similarity analyses of stereoelectronic properties such as structural parameters, atomic charges, dipole moments, molecular electrostatic potentials, and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were performed on JH, JH-mimic, and the DEET compounds. Similarity of stereoelectronic attributes of the amide/ester moiety, negative electrostatic potential regions beyond the molecular surface, and a large distribution of hydrophobic regions in the compounds appears to be the 3 important factors leading to a similar interaction with the JH receptor. The similarity of electrostatic profiles beyond the molecular surface is likely to play a crucial role toward molecular recognition interaction with the JH receptor from a distance which suggests a possible electrostatic bioisosterism of the amide group of the DEET compounds and JH-mimic and, thus, a model for molecular recognition at the JH receptor.

Aedes↗
PubMed2004

Interaction between ferric ions, phospholipid hydroperoxides, and the lipid phosphate moiety at physiological pH.

Iron-catalyzed lipid peroxidation was examined using 1H NMR in a biphasic aqueous-chloroform system. At physiological pH (7.4), mole ratios of phospholipids/Fe3+ as low as 1300:1 catalyzed the rapid disappearance of endogenous lipid hydroperoxides with a loss of two of the four double bonds in PC containing palmitic (16:0) and arachidonic (20:4) acids in the sn-1 and sn-2 positions, respectively. The predominant phospholipid products after 1 h at 20 degrees C were a 9-carbon mono-unsaturated carbonyl and a phospholipid with an 11-carbon delta5,8 FA in the sn-2 position. PC with linoleic acid (18:2) in the sn-2 position lost one double bond and formed a phospholipid with a 9-carbon FA. Cardiolipin (linoleic acid-rich) also lost about 40% of its double bonds. No detectable loss was seen for PC containing oleic acid (18:1) or neutral lipids with PUFA. At arachidonyl PC/Fe3+ ratios less than 20:1, significant broadening of the choline methyl proton peak was evident, indicating that Fe3+ may form a complex with the adjacent phosphate group and that the complex involves both the phosphate and the hydroperoxide adjacent to the delta11 double bond. The results demonstrate that, at physiological pH, Fe3+-catalyzed peroxidation in polyunsaturated phospholipids occurs selectively adjacent to specific double bonds (delta9 or delta11). These PC-derived products have been shown to activate components of the inflammatory system. This suggests that the episodic release of ferric ions may play a significant role in generating inflammatory mediators.

Arachidonic Acid↗
PubMed2004

Evaluation of trans-scleral diode laser using diopexy probe for subfoveal choroidal neovascular membrane in age-related macular degeneration.

OBJECTIVE: To evaluate safety and short-term visual and fluorescein angiographic effects of trans-scleral diode laser photocoagulation in patients with subfoveal choroidal neovascularization from age-related macular degeneration (ARMD). BACKGROUND DATA: The visual outcome following treatment of subfoveal choroidal neovascularization in ARMD is still unsatisfactory. Various forms of therapy such as laser treatment, photodynamic therapy, radiation therapy, transpupillary thermotherapy, and surgical excision have been tried with variable results. MATERIALS AND METHODS: Patients with subfoveal choroidal neo-vascularization were treated with trans-scleral diode laser using the diopexy probe under indirect ophthalmoscopic visualization and followed up at 2, 6, and 12 weeks. Standardized protocol refraction, visual acuity testing, reading speed, contrast requirement measurement, ophthalmic examinations, color fundus photographs, and fluorescein angiogram were used to evaluate the results of treatment. RESULTS: Eighteen eyes of 18 patients were included in the study between April 2000 and May 2002. At 12 weeks, 81.5% patients showed stabilization (+/-5 letters) in letter visual acuity score, and one patient showed improvement (gain of more than five letters) in letter visual acuity score. Reading speed levels and contrast requirement were found to be similar to pre-laser level at 3 months followup. At 12 weeks, moderate fluorescein leakage was seen in one eye, minimal leakage was seen in five eyes, absence of leakage was seen in 10 eyes, and progression was seen in two eyes. CONCLUSION: Transcleral diode laser treatment of subfoveal choroidal neovascular membranes in ARMD may be an effective as well as safe alternative in the management of these patients.

Aged↗
PubMed2003

Diagnostic value of needle aspiration cytology (NAC) in the assessment of palpable inguinal lymph nodes: a study of 210 cases.

The aim of this study was to evaluate the diagnostic value of needle aspiration cytology (NAC) in the assessment of palpable inguinal lymph nodes, which were analyzed in 210 cases. NAC in all the cases were performed by the conventional aspiration method and cytologic examination was done on site after staining smears with the Papanicolaou method. In addition, Diff-Quik-stained air-dried smears, Papanicolaou-stained fixed smears, and filter preparations from needle washings and hematoxylin-eosin-stained sections of cell blocks were studied. The NAC diagnosis was supported by examining cell blocks in 92/210 cases which showed a reliable histologic architecture; further support was also obtained with a tissue biopsy in 9/12 cases of inflammatory lesions, 7/7 cases with a suspicious diagnosis, 20/26 cases of melanomas, 15/15 cases of lymphomas, and/or a comparison with the primary tumor in other cases of metastatic tumors. Additionally, immunoperoxidase and/or histochemical stains were done. Twelve cases were diagnosed as inflammatory lesions and 88 cases were regarded as negative (normal cellular elements n = 40; reactive elements n = 48). In 58 cases a variety of metastatic tumors were diagnosed (melanoma n = 26; others n = 32) and in 15 cases a diagnosis of lymphoma was made. Seven cases were diagnosed as suspicious of malignancy and 30 cases were unsatisfactory due to scanty/acellular samples (despite 2-3 repeat samplings). However, in five of these malignant tumors were later found on a biopsy which was done due to a persistent and continued enlargement of lymph node(s). The sensitivity was 91.7%, specificity 98.2%, positive predictive value (PPV) 97.7.%, and negative predictive value (NPV) was 95.45%. Based on our study we feel that NAC as a first line of investigation is not only useful in the diagnosis of lesions in inguinal lymph nodes, but can also help in deciding on an appropriate management. Also, histologic architecture from cell blocks can be correlated with cytology and such material can be used for histochemical and immunomarker studies.

Adolescent↗
PubMed2003

Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: possible links to hypertension, atherogenesis, and stroke.

Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.

Animals↗
PubMed2002

Aspiration cytodiagnosis of amyloid from vitreous fluid.

Amyloidosis of the vitreous body is a rare disorder that causes progressive visual loss. In this report, a 36-yr-old female with familial amyloidosis is described in whom a progressive reduction of vision in both eyes over the last 4 yr was ascribed to vitreous opacities due to amyloid. A left pars plana vitrectomy was performed and an aspirated sample of the vitreous on cytologic examination showed vitreous strands admixed with abundant dense, pink, globular material which was intensely positive on Congo red staining and exhibited yellowish-green birefringence indicative of amyloid. This was further confirmed ultrastructurally, which showed the classical appearance of amyloid fibrils. The case is of interest not only in view of the rarity of the condition but also in view of the fact that as far as we are aware the cytodiagnosis of amyloid from an aspirate sample from the vitreous has not been previously described in the literature.

Adult↗