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D De

Publications and source records attributed to D De.

14 recordsLinked to original sources

Comparative efficacy of Hanifin and Rajka's criteria and the UK working party's diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in North India.

BACKGROUND: Diagnosis of atopic dermatitis (AD) depends on clinical features because no definitive diagnostic test exists. Criteria proposed by Hanifin and Rajka (Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-47) were acceptable for hospital-based studies but were found not to be suitable for field studies. A UK working party formulated clinical diagnostic criteria that could be used in both hospital and epidemiological settings. Validation studies of the criteria showed widely variable results, probably due to different clinical settings and ethnicity. AIM AND OBJECTIVE: This study was undertaken to validate Hanifin and Rajka's criteria and to assess the comparative efficacy of their criteria and the UK working party's diagnostic criteria in the diagnosis of AD in a hospital setting in North India. SUBJECTS AND METHODS: This study serially included 101 patients with AD and 48 controls of paediatric age group. The study period was from July 2003 to December 2004. RESULTS: Hanifin and Rajka's criteria (sensitivity 96%, specificity 93.75%, positive predictive value 97% (PPV) and negative predictive value (NPV) 91.84%) had a statistical advantage over the UK working party's diagnostic criteria (sensitivity 86%, specificity 95.83%, PPV 97.75% and NPV 76.67%), with a P-value < 0.005.

Adolescent↗

Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ-13.

AQ-13 ([N1-(7-chloro-quinolin-4yl)-3-(N3,N3-diethylamino)propylamine] dihydrochloride trihydrate) is an aminoquinoline antimalarial drug that is effective against chloroquine-resistant strains of Plasmodium falciparum. It is structurally similar to the widely used chloroquine diphosphate (CQ). We evaluated these drugs in the three assays currently recommended by the International Conference on Harmonization (ICH): bacterial mutagenesis in Salmonella typhimurium and Escherichia coli, mammalian cell mutagenesis in L5178Y mouse lymphoma cells, and micronucleus induction in rat bone marrow. A small but statistically significant increase in revertant colonies was produced by CQ with Salmonella tester strain TA98 without metabolic activation (MA) and by AQ-13 with strain TA1537 both with and without MA. In L5178Y cells, testing of CQ and AQ-13 up to cytotoxic concentrations with and without MA produced no increase in mutant colonies and no increase in the numbers of small colonies. Slight decreases in the ratio of polychromatic erythrocytes (PCE) to red blood cells (RBC) were observed in male and female rats treated with CQ and in females only treated with AQ-13; however, none of these changes was statistically significant. No increases in the frequency of micronucleated PCE were observed at any dose level of CQ or AQ-13. Although both CQ and AQ-13 showed weak bacterial mutagenicity, this mutagenic effect was not confirmed in either the mouse lymphoma mutagenesis assay or the micronucleus assay. These results indicate that CQ and AQ-13 should pose minimal risk of genotoxic damage in human populations being administered these drugs.

Animals↗

Structure-activity relationships for antiplasmodial activity among 7-substituted 4-aminoquinolines.

Aminoquinolines (AQs) with diaminoalkane side chains (-HNRNEt2) shorter or longer than the isopentyl side chain [-HNCHMe(CH2)3NEt2] of chloroquine are active against both chloroquine-susceptible and -resistant Plasmodium falciparum. (De, D.; et al. Am. J. Trop. Med. Hyg. 1996, 55, 579-583). In the studies reported here, we examined structure-activity relationships (SARs) among AQs with different N, N-diethyldiaminoalkane side chains and different substituents at the 7-position occupied by Cl in chloroquine. 7-Iodo- and 7-bromo-AQs with diaminoalkane side chains [-HN(CH2)2NEt2, -HN(CH2)3NEt2, or -HNCHMeCH2NEt2] were as active as the corresponding 7-chloro-AQs against both chloroquine-susceptible and -resistant P. falciparum (IC50s of 3-12 nM). In contrast, with one exception, 7-fluoro-AQs and 7-trifluoromethyl-AQs were less active against chloroquine-susceptible P. falciparum (IC50s of 15-50 nM) and substantially less active against chloroquine-resistant P. falciparum (IC50s of 18-500 nM). Furthermore, most 7-OMe-AQs were inactive against both chloroquine-susceptible (IC50s of 17-150 nM) and -resistant P. falciparum (IC50s of 90-3000 nM).

Aminoquinolines↗

Reduction of Platelet Thrombi and Emboli by L-Arginine during Cardiopulmonary Bypass in a Pig Model.

We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650-780 µCi) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30-35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT > 400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m2), and an arterial filter (AF: 0.25 m2, Bentley) at a blood flow of 2.5-3.5 l/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean +/- SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140:control) of porcine platelets was carried out with blood samples taken before, during, and after CPB. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hip pocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5-10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.

Journal Article↗

Enterotoxigenic Escherichia coli associated diarrhoea among infants aged less than six months in Calcutta, India.

The role of enterotoxigenic Escherichia coli (ETEC) as etiologic agents of diarrhoea in infants aged less than six months was assessed in a hospital based study in Calcutta, India. Of the 218 cases examined, ETEC strains were isolated from 26 (11.9%) cases. Among these, in 17 cases ETEC was the sole infecting pathogen (p = 0.0085). Of the 26 isolates (each isolate representing a case), 24 were distributed among seven different O:K:H serotypes and two different colonization factor antigens (CFAs) I and II. Two of the remaining isolation were untypable, non-haemagglutinating, and were non-hydrophobic as measured by the salt aggregation test (SAT). Of the 26 ETEC strains detected, 15 (57.7%) produced heat-labile toxin (LT) only, 8 (30.8%) liberated heat-stable toxin (ST) only, and the remaining 3 (11.5%) produced both LT and ST. No ETEC strain was isolated from the 102 age-matched controls included in this study. All the ETEC isolates were multiple drug resistant. The study showed that the diarrhoea due to ETEC was of brief duration, mostly within the range of 3 to 7 days.

Anti-Bacterial Agents↗

Aminoquinolines that circumvent resistance in Plasmodium falciparum in vitro.

Aminoquinoline (AQ) resistance is one of the most important factors in the worldwide resurgence of malaria due to Plasmodium falciparum. We synthesized a series of AQs to define the structure-activity relationships responsible for AQ action against chloroquine-susceptible and -resistant P. falciparum. The AQs with ethyl, propyl, isopropyl, butyl, pentyl, isopentyl (chloroquine), hexyl, octyl, decyl, or dodecyl side chains were equally active against chloroquine-susceptible P. falciparum (50% inhibitory concentrations [IC50s] = 5-15 nM). The AQs with ethyl, propyl, isopropyl, decyl, or dodecyl side chains were also active against chloroquine-, mefloquine- and multiply-resistant P. falciparum (IC50s = 5-20 nM). Verapamil, which enhances the activity of chloroquine against chloroquine-resistant parasites, had no effect on the activity of AQs that were active against resistant parasites. These results indicate that AQs with 2-12 carbon side chains are as active as chloroquine against chloroquine-susceptible P. falciparum, and that AQs with side chains shorter or longer than chloroquine are often active against chloroquine-, mefloquine-, and multiply-resistant P. falciparum.

Aminoquinolines↗

Shigellosis in Calcutta during 1990-1992: antibiotic susceptibility pattern and clinical features.

Of 230 cases of bloody diarrhoea studied, 100 (43.5%) were positive for Shigellae by stool culture, of which Shigella dysenteriae type 1 was isolated from 56 cases, S. flexneri from 35, S. boydii from 5 and S. sonnei from 4. The major clinical manifestations of the patients infected with Shigella spp. were abdominal pain, anorexia, vomiting, tenesmus, and fever. Fever of above 100.5 degrees F and frequency of stool of more than 15 per day were noticed more among cases infected with S. dysenteriae type 1 and S. flexneri. Vomiting was more frequently observed in cases infected with S. sonnei or S. boydii (44.4%) as compared to those infected with S. dysenteriae type 1 (10.7%) and S. flexneri (8.6%). All Shigella isolates were uniformly susceptible to norfloxacin and ciprofloxacin but were resistant to streptomycin. S. dysenteriae type 1 isolates were susceptible to nalidixic acid (69.6%), ampicillin (5.4%), TMP-SMX (12.5%), furazolidone (98.2%) and gentamycin (80.4%), whereas all other Shigella isolates (S. flexneri, S. boydii, and S. sonnei) were uniformly susceptible to nalidixic acid, > 94% susceptible to furazolidone, and only moderately susceptible to ampicillin (28.6% to 55.5%) and TMP-SMX (22.2% to 48.6%).

Adult↗

A novel pyrrolidonoalkaneamine (WR268954) that modulates chloroquine resistance of Plasmodium falciparum in vitro.

With the recent observations of efflux of chloroquine from Plasmodium falciparum and modulation of chloroquine resistance by calcium channel blockers, such as verapamil, a great deal of attention has been focused on the development of new modulators that can potentiate the efficacy of chloroquine. We report a new compound, WR268954, that has weak intrinsic antimalarial activity compared to chloroquine. In vitro, it increased the susceptibilities of chloroquine-resistant P. falciparum strains to chloroquine and quinine, but did not affect the chloroquine-susceptible strains. In the presence of 2,000 nM of WR268954, the 50% inhibitory concentration of chloroquine for drug-resistant P. falciparum decreased 90-fold in comparison with the control (chloroquine only). The same concentration of WR268954 increased the potentiation of chloroquine in resistant strains to a level approximately equivalent to that observed for the sensitive strain. This compound also potentiates the efficacy of quinine in drug-resistant parasites. However, WR268954 did not enhance the efficacy of mefloquine in the mefloquine-resistant parasites. In this report, the data show the synergistic effect of WR268954 on the antimalarial activity of chloroquine in drug-resistant strains of P. falciparum, but only an additive effect on drug-sensitive strains of parasites. Compound WR268954 belongs to a pyrrolidino alkane amine class whose in vitro chloroquine resistance modulator activity supports the basis for the synthesis of this class of compounds.

Animals↗

Regioselective reactions of 1,2-dehydroprogesterone: syntheses of pregnane derivatives as possible contragestational agents.

A few pregnane derivatives were synthesized from 1,2-dehydroprogesterone (1). Ring A of 1,2-dehydroprogesterone was aromatized without affecting C-20, and the resulting acetoxy compound (2) after hydrolysis yielded 1-hydroxy-4-methyl-19-norpregna-1,3,5(10)-trien-20-one (3). Reactions of the phenol (3) with alkyl halides yielded the ethers 6a-6b and 7. Opening of the oxirane ring in 7 with secondary amines furnished the aminoalcohols 8a-8b. Friedelcraft's reaction of 3 with maleic anhydride and chloracetyl chloride led to the formation of 9 and 10, respectively. Base-catalyzed ring closure of 10 yielded 1-acetyl-12a-methyl-8-oxo-5[H]-1,2,3,3a,3b,4,8,9,10b,11,12, 12a-dodecahydrocyclopenta (7,8)-phenanthro (3,4-b) furan (11), which reacted with aromatic aldehydes regioselectively to furnish 12a-12b. Reaction of 1 with triethylorthoformate in the presence of boron trifluoride etherate involved the participation of C-21, and the carbonyl at C-3 remained unaffected. The product 13 was identified as 21-[2-hydroxyvinyl]-21-norpregna-1,4-diene-3,20-dione. Reductive amination with sodium cyanoborohydride in the presence of ammonium acetate did not attack ring A and smoothly furnished the amine 14 which, on reaction with succinic anhydride, gave 20-succinamylpregna-1,4-dien-3-one (15).

Chemical Phenomena↗

Wilm's tumour.

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Child↗

Reduction of neutrophil margination by L-arginine during hypothermic cardiopulmonary bypass in a pig model.

Nitric oxide generation by L-arginine (2 mg/kg/min) infusion during cardiopulmonary bypass (CPB) increases blood flow to all organs and reduces cytokine induced organ damage by reducing the level of marginating neutrophils (Ns). The N-trapping in the oxygenator (OX), arterial filter (AF), cardiotomy reservoir (CR), and N-margination were quantified with indium 111 labeled autologous neutrophils (INN) in nine groups of 40 Yorkshire pigs (30-35 kg). Cardiopulmonary bypass (180 min or 90 min CPB, 90 min reperfusion) was carried out at 2.5-3.5 L/min and at two temperatures (18 degrees C, 28 degrees C). The INN (650-780 microCi) was administered intravenously 15 mins before CPB. All pigs received heparin systemically (activated coagulation time > 400 secs); CPB was instituted with a roller pump, OX (Univox 1.8 m2), AF (0.25 m2), and CR (BCR-3500, Bentley Lab, Irvine, CA). The INN distribution in the device (OX, AF, CR) and organs was imaged with a gamma camera and measured with an ion chamber and a gamma counter. The LA infusion decreased N-trapping, estimated as the percent of injected INN (mean +/- standard deviation), in OX from control (2.7 +/- 2.02)% to (0.94 +/- 0.29)%, and margination in lung from control (48 +/- 4)% to minimal levels (23 +/- 2)% (p < 0.01). In the CPB reperfusion group, a beneficial effect was observed at LA low dose and toxicity of higher N-margination at 15 mg/ kg/min. Neither CPB temperature nor Leumedin affected N-margination significantly.

Animals↗

Emboli from an extraluminal blood flow hollow fiber oxygenator with and without an arterial filter during cardiopulmonary bypass in a pig model.

The effect of an arterial filter on visceral emboli was quantified with autologous indium-111 labeled platelets (INPLT) during cardiopulmonary bypass (CPB) in Yorkshire pigs. Biodistribution of INPLT was determined in 12 control pigs (30-35 kg, unoperated control [n = 6] and sham operated control [n = 6]). CPB was carried out with (n = 6) and without (n = 6) an arterial filter in 12 pigs at a flow rate of 2.5-3.5 L/min. Platelets labeled with In-111 tropolone (650-780 microCi) were injected intravenously 24 hr before CPB. All pigs were systemically heparinized (activated coagulation time > 400 sec); CPB was instituted with a roller pump, an extraluminal blood flow oxygenator (Bentley Univox, 1.8 m2), and an arterial filter (0.25 m2) and continued for 3 hr. Platelet kinetics, pooling, and counts were monitored by a Geiger probe and a Coulter counter. The thrombi in the oxygenator and arterial filter and emboli in viscera and brain were imaged with a gamma camera and measured with an ion chamber and gamma counter. Percentage of INPLT (mean +/- SD) in organs, tissues, and components of the circuit in four groups of pigs was calculated. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140: control) of porcine platelets was carried out with blood samples taken before, during, and after CPB for estimation of circulating platelet aggregates and platelet microparticles. Pulmonary, renal, cardiac, and cerebral emboli in pigs undergoing CPB with and without a filter were similar (p < 0.1). The amount of filter adherent thrombi was small (0.04 +/- 0.01%); oxygenator adherent thrombus in both groups was similar (p < 0.1). Emboli were found in the cerebral medulla, hippocampus, and posterior cerebral cortex in both groups. During CPB, the arterial filter functioned minimally as a trap for platelet thrombi detached from the oxygenator and circulating emboli. Flow cytometry of blood demonstrated the shift of equilibria from single platelets to platelet aggregates and microparticles during CPB and their gradual reversal to single platelets after CPB; the loosely adherent emboli disaggregated and further shifted these equilibria to single platelets and smaller aggregates, probably through the action of endogenous nitric oxide and prostacyclin. The emboli were trapped in organs and tissues and microparticles were sequestered by the reticuloendothelial system.

Animals↗