Synthesis of some bisindolyl analogs for in vitro cytotoxic and DNA cleavage studies

One-pot, three components, conventional and microwave-assisted synthesis of bisindolyl analogs is described. Michael addition of preformed 2,5-disubstituted indole-3-carboxaldehydes and 3-methyl-1H-pyrazol-5(4H)-one with 2,5-disubstituted indoles under solvent and catalyst-free conditions afforded the hitherto unreported 2,5-disubstituted bisindolyl analogs bearing a pyrazolone moiety in excellent yields. All the synthesized compounds were characterized using IR, ¹H NMR, mass spectral, and analytical data. The analogs were screened for in vitro cytotoxic and DNA cleavage studies. Among the screened compounds 4c, 4f, and 4h–4j have emerged as most potent cytotoxic and 4c and 4f–4h as active DNA cleavage analogs.     

Is bleach-sedimented smear microscopy an alternative to direct microscopy under programme conditions in India?

This cross-sectional multi-centric study compared the yield of and potential benefit for detecting smear-positive pulmonary tuberculosis (PTB) by bleach sedimentation (2% sodium-hypochlorite) versus direct microscopy under programme conditions in India. Among 3168 PTB suspects, 684 (21.6%) were detected by bleach sedimentation vs. 625 (19.7%) by direct microscopy, with a proportional overall agreement of 96% (κ = 0.88). While 594 patients were smear-positive with both methods, 31 patients detected by direct microscopy were missed and an additional 90 patients were detected by bleach sedimentation. Overall, bleach sedimentation increased the yield of smear-positive TB detection; however; it also increased the time to results.     

Synthesis of biphenyl derivatives as ACE and α-amylase inhibitors

Angiotensin converting enzyme (ACE) and α-amylase inhibitors were synthesized using 4′-(bromomethyl)-biphenyl-2-carbonitrile 1 and various cyclic secondary amines (a–h). The nitrile group appended to biphenyl was converted into tetrazole 3a–3h and the tetrazole was ring transformed into 1,3,4-oxadiazole derivatives 4a–4h. Some of the compounds have exhibited significant ACE and α-amylase inhibition.     

Human leukocyte response to an endurance race

Summary The response of circulating leukocytes (WBC's) with regard to changes in number, proportion of neutrophils versus lymphocytes and changes in lymphocyte function as well as proportions of T and B cells was studied in eleven men who ran a 20-mile race. A marked leukocytosis was noted 10–15 min after the race with the predominant increase being polymorphonuclear leukocytes (P<0.001). A significant rise in mean serum cortisol levels was also noted (P<0.001) which correlated with both the increase in total WBC's (P< 0.001) and granulocytes (P<0.001), but not lymphocytes. The increase in serum cortisol was inversely correlated with miles of prior training (P<0.001). An increase in lymphocytes from 1767±112/mm³ to 2431±202/mm³ was less than that previously described in short-term exercise. As with short-term exercise the most significant increase in lymphocytes was in B lymphocytes bearing surface immunoglobulin (P<0.0025). However, in contrast to short-term exercise lymphocytes maintained good in vitro response to the mitogen phytohemagglutinin.This study demonstrates that endurance racing produces a more marked granulocytosis and less lymphocytosis than short bouts of exercise. It is suggested that the degree of leukocytosis is stress dependent in that it was positively correlated with serum cortisol and inversely correlated with prior training.Supported in part by a joint fellowship from the National and Wisconsin Kidney Foundations     

Reduction of abdominal fat and chronic disease factors by lifestyle change in migrant Asian Indians older than 50 years

The objective of this study was to assess the impact of a group diet and physical activity intervention on body composition, blood lipid profile and insulin resistance in migrant Asian Indian volunteers. Total body and abdominal fat, waist girth, serum glucose, insulin and lipids were measured one month before and immediately prior to an intervention designed to encourage increased physical activity and improved diet. Measurements were repeated after a 5-month period of altered exercise and dietary habits. Over this period monthly group education sessions were held on diet and physical activity and the importance of lifestyle changes to reduce risk factors for chronic disease. Forty one (21M, 20F) volunteers (aged > 50 y) were recruited from Asian Indian community groups in urban Auckland, New Zealand. Body weight, total and percentage body fat, waist girth and abdominal fat decreased in men following the intervention (p < 0.006) while these changes were not statistically significant in women. In both men and women high density lipoprotein (HDL) levels increased and LDL and total cholesterol/HDL ratio decreased (p < 0.002) without changes in serum glucose, insulin and triglycerides. Reduction in systolic and diastolic blood pressure was associated with an increase in HDL cholesterol in women (r = 0.63, p = 0.003, r = 0.48, p = 0.03) but not in men (r = 0.09, p = 0.69, r = 0.04, p = 0.86). Over a five month period, an Asian Indian community group diet and physical activity intervention resulted in significant reductions in total and abdominal body fat and blood lipid risk factors but not in insulin sensitivity or resistance.     

A leak quantification method using sulfur hexafluoride as tracer gas

Filter holders and continuous air monitors are used extensively in the nuclear industry. It is important to minimize leakage in these devices, and, in recognition of this consideration, a limit on leakage for sampling systems is specified in; however, the protocol given in the standard is really germane to measurement of significant leakage, e.g., several percent of the sampling flow rate. In the present study, we developed a technique for quantifying leakage and used that approach to measure the sealing integrity of a continuous air monitor and two kinds of filter holders. The methodology involves use of sulfur hexafluoride as a tracer gas with the device being tested operated under dynamic flow conditions. The leak rates in these devices were determined in the pressure range from 2.49 kPa (10 inches H2O) vacuum to 2.49 kPa (10 inches H2O) pressure at a flow rate of 56.6 L min-1 (2 cfm). For the two filter holders, the leak rates were less than 0.007% of the nominal flow rate. The leak rate in the continuous air monitors was less than 0.2% of the nominal flow rate. These values are well within the limit prescribed in the ANSI standard, which is 5% of the nominal flow rate. We suggest that the limit listed in the ANSI standard should be reconsidered as lower values can be achieved, and the methodology presented herein can be used to quantify lower leakage values in sample collectors and analyzers.     

Protective effect of embelin against acetic acid induced ulcerative colitis in rats

The aim of the present study is to evaluate the effect of embelin isolated from Embelia ribes on acetic acid induced colitis in rats. Experimental animals received embelin (25 and 50 mg/kg, p.o.) and sulfasalazine (100 mg/kg, p.o.) for five consecutive days before induction of colitis by intra-rectal acetic acid (3% v/v) administration and the treatment continued up to 7 days. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. Embelin treatment significantly decreased clinical activity score, gross lesion score, percent affected area and wet colon weight when compared to acetic acid induced controls. The treatment also reduced significantly the colonic myeloperoxidase activity, lipid peroxides and serum lactate dehydrogenase and significantly increased the reduced glutathione. The histopathological studies also confirmed the foregoing findings. The protective effect may be due to its antioxidant and anti-inflammatory activities.     

Development of Press-Coated,Floating-Pulsatile Drug Delivery of Lisinopril

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.     

Role of cyclodextrin complexation in felodipine-sustained release matrix tablets intended for oral transmucosal delivery: in vitro and ex vivo characterization

The objective of the present research was two-fold: To characterize the produced inclusion complex of felodipine (FDP)-hydroxypropyl-β-cyclodextrin (HPβCD) utilizing lyophilization, and to develop and characterize a complexed sustained-release polymeric matrix tablets intended for buccal delivery. The phase-solubility diagram suggested an A(L) type system with 1:1 stoichiometry. Solid complexes prepared by physical mixing and lyophilization were characterized by thermal and non-thermal analytical techniques to corroborate the fact of complex formation. The sustained-release FDP tablets were produced by direct compression, and these drug or complex-loaded hydrophilic matrices were assessed for in vitro bioadhesion and release modulation, ex vivo permeation, and in vivo residence time. The in vitro drug release and ex vivo permeation across the porcine buccal membrane demonstrated that the matrix tablets containing FDP-HPβCD (FH5) solid complex exhibited a complete and sustained drug release pattern, and a significantly higher drug permeation (p?相似文献