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991.
Noorullah Naqvi Mohammed Pankaj Pandey Nayaab S. Khan Khaled M. Elokely Haining Liu Robert J. Doerksen 《Pharmaceutical development and technology》2016,21(5):619-629
Clotrimazole (CT) is a poorly soluble antifungal drug that is most commonly employed as a topical treatment in the management of vaginal candidiasis. The present work focuses on a formulation approach to enhance the solubility of CT using cyclodextrin (CD) complexation. A CT–CD complex was prepared by a co-precipitation method. Various characterization techniques such as differential scanning calorimetry, infrared (IR) and X-ray spectroscopy, scanning electron microscopy and nuclear magnetic resonance (NMR) spectroscopy were performed to evaluate the complex formation and to understand the interactions between CT and CD. Computational molecular modeling was performed using the Schrödinger suite and Gaussian 09 program to understand structural conformations of the complex. The phase solubility curve followed an AL-type curve, indicating formation of a 1:1 complex. Molecular docking studies supported the data obtained through NMR and IR studies. Enthalpy changes confirmed that complexation was an exothermic and enthalpically favorable phenomenon. The CT–CD complexes were formulated in a gel and evaluated for release and antifungal activity. The in vitro release studies performed using gels demonstrated a sustained release of CT from the CT–CD complex with the complex exhibiting improved release relative to the un-complexed CT. Complexed CT–CD exhibited better fungistatic activity toward different Candida species than un-complexed CT. 相似文献
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The genetic association strategy is currently being applied to a number of psychiatric phenotypes including disease vulnerability, personality variation and clinical response to psychotropic drugs. Association studies offer the prospect of identification of the specific alleles that confer significant effects on clinical phenotype. However, it should be noted that this strategy has additional advantages as well as unique drawbacks. In this paper, we review the basic methodology utilized in each step of a typical psychiatric genetic association study and discuss their potential benefits and pitfalls with particular emphasis on the selection of clinical phenotype, the identification of a candidate gene, the selection of a candidate variant, clinical data set design, and the statistical analysis of association data. With appropriate design and execution, it is hoped that the association strategy will prove to be as successful in psychiatry as it has proven to be in other branches of medicine. 相似文献
996.
Serum Insulin and Lipid Profile in Normal Pregnant and Pregnancy-Induced Hypertensive Women from North India 总被引:4,自引:0,他引:4
Chandana Tripathy MD Sunita Malik MD Pankaj Shah MD DM R. Lakshmy PhD Devjit Tripathy MD DM 《The Australian & New Zealand journal of obstetrics & gynaecology》1999,39(3):321-323
High serum insulin and lipoproteins have been reported in pregnancy-induced hypertension. Little is known about the insulin and lipoprotein profile in Indian women. To address this question we compared serum insulin and lipoproteins of women with pregnancy induced hypertension (PIH) and normotensive pregnant women. The serum insulin, triglycerides, total cholesterol and HDL cholesterol of 104 women with PIH were compared with 99 control women. Hypertensive women had significantly higher insulin (53.94 +/- 29.58 versus 37.69 +/- 17.39 pmol/L, p=0.0004) and triglyceride (3.27 +/- 1.2 versus 2.66 +/- 0.6, p=0.0001). There was no significant difference in total cholesterol and HDL cholesterol levels. Insulin levels had a positive correlation with systolic blood pressure (r=0.64) and diastolic blood pressure (r=0.55) in women with PIH. These differences persisted even after adjusting for possible confounding variables such as age, body mass index and the period of gestation. We conclude that elevated serum insulin values or insulin resistance may contribute to the pathogenesis of PIH in Indian women. 相似文献
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998.
Dilip K. Das Ajay K. Gupta Veena Chowdhury Deepak K. Satsangi Sanjay Tyagi Jagdish C. Mohan Vijay A. Khan Veena Malhotra 《Diagnostic cytopathology》1997,17(2):143-147
A 45-yr-old female presented with a left upper cervical swelling of 4 yr duration. The clinical suspicion of carotid body tumor (CBT) was confirmed by imaging findings, fine-needle aspiration (FNA) cytology, and histology of the resected tumor. Review of our experience with four cases including the present one during 10 yr (1984–1994) showed that the age of the patients ranged from 35 to 45 yr with a mean of 40.8 yr. All four cases were females and had left-sided upper cervical swelling. Clinically one case was diagnosed as cervical lymphadenopathy and there was clinical suspicion of CBT in two cases. Findings of digital subtraction angiogram in four cases and ultrasonography including Doppler ultrasound vascular imaging in three cases were consistent with CBT. The cytodiagnosis was CBT in three cases and inadequate (blood only) in one case. The analysis of detailed cytologic features in three cases revealed blood-rich aspirate with poor to moderate cellularity, indistinct cell outline, and acinar formation. Giant bare nuclei, spindle-shaped tumor cells, and cytoplasmic granulations were observed in two cases each. Histopathology of the resected tumors in two cases confirmed the cytodiagnosis of CBT. FNA cytology played a useful role in arriving at a tissue diagnosis of this rare neoplasm. Diagn. Cytopathol. 17:143–147, 1997. © 1997 Wiley-Liss, Inc. 相似文献
999.
Annmarie L. Sabb Reinhardt P. Stein Robert L. Vogel Rene Tasse Susan Amburn Denise K. Fairman Dianne Kowal Deepa Malhotra Carl A. Boast Adam Bartolomeo Herman Morris Tracy Sailer John A. Moyer Magid Abou-Gharbia Douglas M. Ho 《Drug development research》1997,40(2):185-192
Computer modeling of carbachol docked in the human m1 receptor binding pocket has been used to discover a series of carbamate and thiocarbamate chiral, conformationally restricted analogues of carbachol based on azabicyclo[2.2.1]heptan-3-ol. These molecules have been evaluated for affinity and efficacy at human muscarinic receptors (m1–m5) transfected into a CHO cell line. None of these compounds was selective in binding. Thiocarbamate analogues had greater affinity for the m1 receptor subtype, but lower efficacy based on comparison of their ability to induce phosphoinositide (PI) turnover. Carbamate analogues had lower affinity for m1 receptors than thiocarbamates and varied in efficacy from 10% to 100% of the carbachol response in phosphoinositide (PI) turnover. One of these analogues 3S,4R-azabicyclo[2.2.1]heptan-3-methylcarbamate, WAY-131256, (VI) has been characterized as an m1/m2 agonist in vitro. (VI) was equi-efficacious to the standard m1 agonist, xanomeline (Phase III) in vivo in a scopolamine-impaired radial arm maze paradigm (MED 1 mg/kg, 5.88 mmol/kg for VI and MED 1 mg/kg, 3.55 mmoles/kg for xanomeline) and was approximately equal to xanomeline in an AF64A-impaired radial arm maze paradigm. Despite its lack of m1 selectivity in vitro, in vivo experiments on (VI) indicated no significant effect on blood pressure or heart rate at 10 mg/kg (58.78 mmol/kg) (i.p.), and no peripheral side effects attributed to stimulation of either the m2 or m3 receptors (salivation, lacrimation, and chromodacryorrhea) up to doses of 30 mg/kg, 176.2 mmol/kg. These results may be explained by different receptor densities in various brain regions not accounted for in a transfected cell line or by metabolism of (VI) to a m1 selective agonist in vivo. Drug Dev. Res. 40:185–192, 1997. © 1997 Wiley-Liss, Inc. 相似文献
1000.
Kenneth Nichols Jacqueline Tamis E. Gordon DePuey Jennifer Mieres Sanjay Malhotra Alan Rozanski 《Journal of nuclear cardiology》1998,5(3):295-303
Objectives Left ventricular volumes and ejection fractions constitute important information in the diagnosis of cardiac disease. This
investigation examined the relations of functional parameters computed with a recently published scintigraphic gated tomographic
method with those from angiography, analyzing discrepancies arising from differences involved in modeling the left ventricle.
Background While left ventricular ejection fractions obtained from myocardial perfusion gated single-photon emission computed tomography
(SPECT) have demonstrated accurate comparisons with other imaging modalities, validations of volumes have not been examined
as extensively, and some recent studies have reported a wide range of angiographic correlation. It is important to know how
volumes obtained by a new class of methods compare with those from older, well-established techniques in order to interpret
individual patients’ results, particularly when scintigraphic images are severely hypoperfused.
Methods and Results Tc-99m sestamibi myocardial perfusion gated SPECT data were processed retrospectively for 58 patients studied by single-plane
angiography. Endocardial borders were generated automatically on paired vertical and horizontal long-axis Tc-99m sestamibi
gated tomograms for computing ventricular volume using a Simpson’s rule summation of elliptical slices. Linear regression
and paired t tests were used to compare SPECT with angiographic parameters for all patients and for groups identified on the basis of
tomogram visual examination as hypoperfused, ischemic or nonischemic, with the latter category further subgrouped as to fixed
defects or normal perfusion. Linear regression analysis demonstrated Pearson correlation coefficients of 0.87 for end-diastolic
volumes, 0.91 for end-systolic volumes, and 0.86 for ejection fraction: paired t test analysis showed end-systolic volumes to be nearly identical (p>0.99) to angiographic values. However, paired t tests also revealed gated SPECT end-diastolic volumes and ejection fractions were significantly lower (p<10-4) than angiography. Correlations and trends were essentially the same for all subgroups except for the small sample (n=10) of patients with normal perfusion.
Conclusions Gated SPECT provides ventricular volumes and ejection fractions that correlate well with angiography, even in hypoperfused
and ischemic populations. However, gated SPECT end-diastolic volumes and ejection fractions are significantly lower than angiographic
measurements, partly because of inclusion of greater outflow tract amounts in standard angiographic models. Because myocyte
concentration decreases rapidly at the ventricular base, it is likely that most gated SPECT methods will produce endocardial
borders encompassing less of the outflow tract than do angiographic outlines.
Supported in part by grants from General Electric Medical Systems, Milwaukee, Wis.
Presented in part at the 46th Annual Scientific Session of the American College of Cardiology, Anaheim, Calif. March 1997. 相似文献