Outbreak of scrub typhus in Andhra Pradesh--experience at a tertiary care hospital.

AIM: To describe the clinical features, laboratory manifestations, complications in patients diagnosed with scrub typhus at a tertiary care hospital in south India. MATERIAL AND METHODS: All cases of acute onset fever diagnosed to have scrub typhus August 2011 to December 2012 were analysed. Cases of scrub typhus confirmed by the well felix test with a titre of 1 in 80 or more and a positive immunochromatography test were studied. RESULTS: 176 confirmed cases of scrub typhus were studied over a period of 18 months. Majority (96%) of patients are from rural background. Farmers constituted 60% of the patients. Most common symptoms were due to the involvement of respiratory tract in the form of cough in 94 (53%) patients followed by breathlessness in 84 (47.7%). Signs of consolidation were seen in 80 (45.5%). Central nervous system involvement in the form of altered sensorium was seen in 43 (24.4%) and seizures in 11 (6.3%) patients. Eshcar was seen in 23 (13%) patients. Transaminases were elevated in 153 (86%) patients, serum alkaline phosphatase in 110 (62.5%) patients. Renal failure was seen in 49 (27.8%) cases and respiratory failure was seen in 11 (6.2%). Eight (4.5%) patients died in our study. CONCLUSION: Scrub typhus should be suspected in patients with rural background with fever and multi system involvement. The predominant symptoms were cough and breathlessness. Central nervous system abnormalities in the form of altered sensorium was seen in 43 (24.4%). Most common laboratory abnormality noted in our patients with scrub typhus was elevated liver enzymes which were seen in 153 (86%) cases.

Phonon-based partition of (ZnSe-like) semiconductor mixed crystals on approach to their pressure-induced structural transition.

The generic 1-bond → 2-mode "percolation-type" Raman signal inherent to the short bond of common A1-xBxC semiconductor mixed crystals with zincblende (cubic) structure is exploited as a sensitive "mesoscope" to explore how various ZnSe-based systems engage their pressure-induced structural transition (to rock-salt) at the sub-macroscopic scale-with a focus on Zn1-xCdxSe. The Raman doublet, that distinguishes between the AC- and BC-like environments of the short bond, is reactive to pressure: either it closes (Zn1-xBexSe, ZnSe1-xSx) or it opens (Zn1-xCdxSe), depending on the hardening rates of the two environments under pressure. A partition of II-VI and III-V mixed crystals is accordingly outlined. Of special interest is the "closure" case, in which the system resonantly stabilizes ante transition at its "exceptional point" corresponding to a virtual decoupling, by overdamping, of the two oscillators forming the Raman doublet. At this limit, the chain-connected bonds of the short species (taken as the minor one) freeze along the chain into a rigid backbone. This reveals a capacity behind alloying to reduce the thermal conductivity as well as the thermalization rate of photo-generated electrons.

Mass-yield distribution of the fission products in fallout from the 14 may 1965 nuclear explosion.

Twenty single particles separated from a 20-liter sample of rain collected in Osaka, Japan, shortly after the 14 May 1965 test explosion of the Chinese nuclear device, were analyzed radiochemically. The abundance pattern of the fission products in these particles resembled the shape of the mass-yield curve for the thermal neutron-induced fission of uranium-235, except for the facts that cesium-hl37 and strontium-90 were markedly depleted and the yields near the symmetric fission region appeared to be somewhat enhanced.

Implication of tryptophan and histidine in the active site of endo-polygalacturonase from Aspergillus ustus: elucidation of the reaction mechanism.

The mechanism of action for the hydrolysis of polygalacturonic acid by the enzyme endo-polygalacturonase (poly(1,4-alpha-D-galacturonide) glycanohydrolase, EC 3.2.1.15) was investigated. The enzyme from Aspergillus ustus was purified to homogeneity and used for the study. The endo-polygalacturonase had a molecular weight of 36,000 daltons, a pI of 8.3, specific activity of 785 units/mg, Km of 0.82 mg/ml, and Vmax of 976 micromoles of product min-1 mg-1. Amino acids involved in the catalysis were identified by chemical modification and the active site characterized. Inhibition by hydroxynitrobenzyl bromide and diethylpyrocarbonate, followed by substrate protection studies showed that tryptophan and histidine were involved at or near the active site. Kinetic constants of partially inhibited enzyme, suggest the involvement of tryptophan in substrate binding and histidine in catalysis. Quenching of tryptophan fluorescence of the enzyme in the presence of polygalacturonic acid substantiated the conclusion that tryptophan was involved in substrate binding. An isotope effect of 1.8 was observed with deuterated water on the Vmax of the endo-polygalacturonase, with the proton inventory giving a linear relationship. The proposed mechanism involves a single proton transfer from the histidine residue of the enzyme to the glycosidic oxygen and hydrolysis by the addition of a water molecule.

A newly synthetic chromium complex--chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance.

Low-molecular-weight organic chromium complexes such as chromium picolinate are often used as dietary supplements to improve insulin sensitivity and to correct dyslipidemia. However, toxicity associated with such chromium compounds has compromised their therapeutic value. The aim of this study was to evaluate the impact of a newly synthesized complex of chromium with phenylalanine, Cr(pa)3 on insulin-signaling and glucose tolerance. Cr(pa)3 was synthesized by chelating chromium(III) with D-phenylalanine ligand in aqueous solution. In mouse 3T3-adipocytes, Cr(pa)3 augmented insulin-stimulated glucose-uptake as assessed by a radioactive-glucose uptake assay. At the molecular level, Cr(pa)3 enhanced insulin-stimulated phosphorylation of Akt in a time- and concentration-dependent manner without altering the phosphorylation of insulin receptor. Oral treatment with Cr(pa)3 (150 microg/kg/d, for six weeks) in ob/ob+/+ obese mice significantly alleviated glucose tolerance compared with untreated obese mice. Unlike chromium picolinate, Cr(pa)3 does not cleave DNA under physiological reducing conditions. Collectively, these data suggest that Cr(pa)3 may represent a novel, less-toxic chromium supplement with potential therapeutic value to improve insulin sensitivity and glycemic control in type II diabetes.

Curcumin inhibits nitrite-induced methemoglobin formation.

Curcumin protects hemoglobin from nitrite-induced oxidation to methemoglobin. The protection is not observed when curcumin is added after the autocatalytic stage of the oxidation of hemoglobin by nitrite. The ability of curcumin to scavenge superoxide may be responsible since superoxide is implicated in promoting the autocatalytic stage of oxidation of hemoglobin by nitrite.

Physico-chemical properties and antioxidant activities of methoxy phenols.

A few structurally related phenols, dehydrozingerone (DZ), bromopentenone (BP), eugenol (EG) and isoeugenol (IEG), derived from plant products show antioxidant properties by inhibiting lipid peroxidation in membrane models. The phenoxyl radicals produced by the scavenging of free radicals during the inhibition of lipid peroxidation, were also generated by specific one-electron oxidants using pulse radiolysis. The radical lifetimes (second order rate constants for radical-radical reactions), reactivities with hydroxyl and model peroxyl radicals and the one-electron reduction potentials with respect to the standard couples were quantified. These results along with their lipophilicity data were correlated with their antioxidant activity (IC50 values).

Purification and characterization of cellular carotenoid-binding protein from mammalian liver.

A cellular carotenoid-binding protein was purified to homogeneity from beta-carotene-fed ferret liver utilizing the following steps: ammonium sulfate precipitation, ion exchange, gel filtration, and affinity chromatography. The final purification was 607-fold. beta-[14C]Carotene copurified with the binding protein throughout the purification procedures. SDS-PAGE of the purified protein showed a single band with an apparent molecular mass of 67 kDa. Scatchard analysis of the specific binding of the purified protein to beta-carotene showed two classes of binding sites; a high-affinity site with an apparent Kd of 56 x 10(-9) M and a low-affinity site with a Kd of 32 x 10(-6) M. The Bmax for beta-carotene binding to the high-affinity site was 1 mol/mol whereas that for the low-affinity site was 145 mol/mol. The absorption spectrum of the complex showed a 32-nm bathochromic shift in lambda max with minor peaks at 460 and 516 nm. Except for alpha-carotene and cryptoxanthin, none of the model carotenoids or retinol competed with beta-carotene binding to the protein. Thus, a specific carotenoid-binding protein of 67 kDa size has been characterized in mammalian liver with a high degree of specificity for binding only carotenoids with at least one unsubstituted beta-ionone ring.

Anticancer and antioxidant activity of synthetic chalcones and related compounds.

Nineteen synthetic chalcones and ten structurally related compounds were investigated for their cytotoxic, tumour reducing and antioxidant activities. Methyl and hydroxy substituted chalcones were found to be cytotoxic in vitro whereas only hydroxy substituted chalcones could reduce ascites tumour in animals. Although most of the compounds analysed showed antioxidant activity, hydroxy and methyl substituted compounds were found to be the most potent antioxidants.

Dehydrozingerone and isoeugenol as inhibitors of lipid peroxidation and as free radical scavengers.

The antioxidant properties of three related compounds, dehydrozingerone, isoeugenol and eugenol, were investigated using various models. Isoeugenol was found to be the most active in inhibiting ferrous-ion-, ferric-ion- and cumene-hydroperoxide-induced lipid peroxidation in rat brain homogenates. These compounds also showed significant hydroxyl radical scavenging activity. Isoeugenol was potent in scavenging superoxide anion generated by the xanthine-xanthine oxidase system, whereas eugenol was found to inhibit xanthine oxidase. The high antioxidant activity of isoeugenol may be due to the presence of a conjugated double bond, which increases the stability of the phenoxyl radical by electron delocalization. Such electron delocalization is not possible with eugenol. In dehydrozingerone, the stability was decreased by an electron withdrawing keto group at the para position.

Chronic ethanol consumption leads to destabilization of rat liver beta-galactoside alpha2,6-sialyltransferase mRNA.

Chronic ethanol consumption in rats is accompanied by decreased levels of Gal beta1,4GlcNAc alpha2,6-sialyltransferase (2,6-ST) activity in the liver. Our previous studies have shown that there is a concomitant decrease in the levels of 2,6-ST mRNA. In this study, the alteration in the regulation of 2,6-ST expression by chronic ethanol consumption was assessed by Northern hybridization, nuclear run-on experiments, and 2,6-ST mRNA stability studies. 2,6-ST downregulation was found at 4 weeks of feeding an ethanol diet (36% of calories from ethanol) and remained up to 8 weeks. The decrease in 2,6-ST mRNA levels was found to be dose-dependent, with lower dose of ethanol (12% and 24% of total dietary calories from ethanol) being ineffective and the effects being manifested only when 36% of the dietary calories were from ethanol. The effects of chronic ethanol feeding could be completely reversed within 1 week after ethanol consumption was stopped, when 2,6-ST mRNA levels were restored to normal. The downregulation was not sensitive to actinomycin D, indicating that the regulation was not affected at the transcriptional level but at the posttranscriptional level. This was confirmed by nuclear run-on experiments showing that the rate of 2,6-ST mRNA transcription was unaffected by ethanol. Finally, mRNA stability experiments showed that the half-life of 2,6-ST mRNA was reduced 50% in ethanol-fed rat livers compared with control rat livers. Taken together, the results show that 2,6-ST mRNA is regulated at the posttranscriptional level and chronic ethanol intake downregulates 2,6-ST expression by destabilizing its mRNA.

Desialylation of human apolipoprotein E decreases its binding to human high-density lipoprotein and its ability to deliver esterified cholesterol to the liver.

Apolipoprotein E (apoE) plays a significant role in the delivery of high-density lipoprotein (HDL) cholesterol to the liver via the apoB/E receptor. The roles of the apoE sialylation status in its association with HDL and in the reverse cholesterol transport (RCT) function of HDL have not been well defined. Furthermore, long-term ethanol treatment impairs apoE sialylation and leads to its decreased content in HDL. Therefore, we investigated the association of either sialo apoE (SapoE) or desialo apoE (DSapoE) with HDL and its effect on the RCT function of HDL. The dextran sulfate precipitation method showed that [125I]DSapoE binding to HDL was 27.3% (P < .02) to 35.5% (P < .001) lower versus [125I]SapoE. Scatchard analysis of the specific binding data showed that [125I]SapoE had 11.2 times more affinity for HDL than [125I]DSapoE based on size-exclusion chromatography (Kd = 89.7 v 1,010 nmol/L). Similarly, [1251]HDL had 4.5 times more affinity for SapoE compared with DSapoE based on solid-phase binding (Kd = 21.9 v 104.4 nmol/L). Furthermore, esterified cholesterol uptake from reconstituted HDL particles (rHDLs) by HepG2 cells increased over basal uptake up to 153% when rHDLs contained SapoE, versus only 37% with DSapoE. Enzymatic resialylation of DSapoE completely restored its HDL-binding and RCT properties, identical to those of SapoE. It is therefore concluded that desialylation of apoE decreases its binding to plasma HDL, leading to an impaired RCT function.

Effect of dietary omega-3 fatty acids and chronic ethanol consumption on reverse cholesterol transport in rats.

We previously showed that chronic ethanol feeding leads to a decrease of apolipoprotein E (apoE) in high-density lipoprotein (HDL), whereas supplementing this diet with 2.8% of total dietary calories as omega3-fatty acids (omega3FAs) restores HDL-apoE to the control values. Since HDL containing apoE plays a major role in reverse cholesterol transport (RCT), we measured the effects chronic ethanol intake and omega3-FAs on RCT in the present study. Four groups of rats, control normal fat (CN), alcohol-normal fat (AN), control omega3FA fat (CF), and alcohol-omega3FA fat (AF), were fed their respective diets for 8 weeks, after which hepatocytes and HDLs from each group were evaluated for RCT capacity (cholesterol efflux from macrophages and uptake by liver cells). Compared with the control diet (CN), chronic ethanol (AN) feeding inhibited the cholesterol efflux capacity of HDL by 21% (P < .01), whereas omega3FA feeding (2.8% of total dietary calories) stimulated this capacity by 79% (P < .01) and 25% (P < .01) in CF and AF rats, respectively. With respect to cholesterol uptake by the liver, there were no significant 3-way or 4-way interactions between the 4 factors, HDL-alcohol, HDL-fish oil, hepatocyte-alcohol, and hepatocyte-fish oil. The main effects for HDL-alcohol, HDL-fish oil, and hepatocyte-alcohol were all highly significant (P = .0001, .0001, and .007, respectively). There was a significant HDL-alcohol and HDL-fish oil interaction (P = .0001). Hepatocyte-alcohol was not a factor in any 2-way interactions. Our study indicates no evidence of an interaction between the effects of omega3FAs and the effects of alcohol on hepatocytes in terms of RCT function. Thus, feeding as little as 2.8% of the total dietary calories as omega3FA not only restored the impaired RCT function of HDL caused by chronic ethanol intake, but also enhanced by severalfold the ability of HDL to promote RCT even in normal animals.

High-density lipoproteins from human alcoholics exhibit impaired reverse cholesterol transport function.

We have previously shown that chronic alcohol consumption leads to inhibition of sialylation of apolipoprotein E (apo E) that results in its impaired binding to high-density lipoprotein (HDL) molecule. Because apo E plays a major role in reverse cholesterol transport (RCT), we speculated that ethanol-mediated formation of HDL molecules without apo E may affect the RCT process. Therefore, we have investigated whether the RCT function of HDL is affected in chronic alcoholics with or without liver disease compared with nondrinkers. HDL was isolated from fasting plasma of normal subjects, n = 9 (nondrinkers), chronic alcoholics, n = 8 (ALC), and chronic alcoholics with liver disease, n = 6 (ALD). A portion of HDL sample from each subject was evaluated for its cholesterol efflux capacity from [3H]cholesterol oleate preloaded mouse macrophages. The remaining portion of each HDL sample was labeled with [3H]cholesterol oleate and evaluated for its ability to deliver cholesterol to the liver using HepG2 cells in culture. Cholesterol efflux capacity of HDLs was decreased by 83% (P < .0002) in alcoholics without liver disease and by 84% (P < .0006) in alcoholics with liver disease compared with the HDLs from nondrinkers. The capacities of HDLs to deliver cholesterol to the liver were decreased by 54% (P < .005) in alcoholics without liver disease and by 64% (P < .005) in alcoholics with liver disease compared with the HDLs from nondrinkers. The fact that further complications by liver disease in alcoholic subjects did not significantly exacerbate the extent of impairment in RCT function of HDL suggest that alcohol per se is responsible for its deleterious effects on RCT. Significantly, plasma HDL apo E concentration relative to that of apo A1 (apo E/apo A1 ratio) was also decreased by 31% to 32% (P < .0005) in alcoholics without or with liver disease compared with nondrinkers. It is therefore concluded that chronic alcohol consumption adversely affects the RCT function of HDL by altering its association with apo E due to ethanol-induced desialylation of apo E.

Antioxidant properties of phenyl styryl ketones.

Phenolic and non phenolic derivatives of phenyl styryl ketones were synthesized and evaluated as in vitro inhibitors of iron and cumene hydroperoxide dependent lipid peroxidation in rat brain homogenates. The compounds were also tested for antioxidant activity in phosphatidylcholine liposomes. Phenyl 3,5-di-tert-butyl-4-hydroxystyryl ketone was found to be the most potent inhibitor of peroxidation among all the compounds tested. It was found to be more active than vitamin E. It also reduced the stable free radical 1,1-diphenyl-2-picrylhydrazyl to an appreciable extent.

Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue.

Free radical reactions of curcumin and its ethoxy substituted derivative (C1) 1,7-bis-(4-hydroxy-3-ethoxy phenyl)-1,6-heptadiene-3,5-dione have been studied using a pulse radiolysis technique in homogeneous aqueous-organic solutions like acetonitrile-water and isopropanol-water mixtures, as well as in neutral TX-100 and cationic CTAB micellar solutions. The phenoxyl radicals of curcumin or C1 were generated by one-electron transfer to several oxidants like N(3)(.), Br(2)(-.), CCl(3)O(2)(.), glutathione radicals which exhibit absorption from a 300-600-nm wavelength region with the maximum at 490-500 nm. Other important properties of the phenoxyl radicals such as extinction coefficient, radical lifetime and their formation and decay rate constants were also determined in these systems. The antioxidant property of curcumin and C1 were estimated in terms of their ability to inhibit the lipid peroxidation in liposomes and also in terms of trolox equivalent antioxidant capacity (TEAC). The results were compared with alpha-tocopherol.

Martian soil component in impact glasses in a Martian meteorite.

Chemical compositions of impact melt glass veins, called Lithology C (Lith C) in Martian meteorite EET79001 were determined by electron microprobe analysis. A large enrichment of S, and significant enrichments of Al, Ca, and Na were observed in Lith C glass compared to Lithology A (Lith A). The S enrichment is due to mixing of plagioclase- enriched Lith A material with Martian soil, either prior to or during impact on Mars. A mixture of 87% Lith A, 7% plagioclase, and 6% Martian soil reproduces the average elemental abundances observed in Lith C. Shock melting of such a mixture of plagioclase-enriched, fine-grained Lith A host rock and Martian soil could yield large excesses of S (observed in this study) and Martian atmospheric noble gases (found by Bogard et al., 1983) in Lith C. These mixing proportions can be used to constrain the elemental abundance of phosphorus in Martian soil.

Regional development and seasonality of communicable diseases in rural Andhra Pradesh, India.

This paper explores the seasonality of morbidity due to communicable diseases in Guntur district in Andhra Pradesh, India. The district has been divided into development regions using cluster analysis. Seasonality of selected communicable diseases is then compared with the levels of development. It is shown that seasonality is most pronounced in the least developed region of the district. In the most developed region, seasonality of morbidity is low. The paper supports the general hypothesis that there is a decreased seasonality of illness as development takes place.

Synthesis and antiinflammatory, analgesic, and antipyretic testing of 4-[1-oxo-(3-substituted aryl)-2-propenyl]-3-phenylsydnones and of 3-[4-[3-(substituted aryl)-1-oxo-2-propenyl]phenyl]sydnones.

Two series of styrylcarbonyl 3-phenylsydnone derivatives, 4-[1-oxo-(3-substituted aryl)-2-propenyl]-3-phenylsydnones (series 1, 1-21) and 3-[4-[3-(substituted aryl)-1-oxo-2-propenyl]phenyl]sydnones (series II, 22-40), were synthesized and evaluated pharmacologically at a dose of 100 mg/kg po. Eleven compounds in series I plus one in series II and six in series I plus seven in series II were active in the carrageenan-induced edema and acetic acid-induced writhing assays, respectively. Compound 35 in the latter assay showed activity somewhat similar to that of the positive control drug, aspirin, administered at the same dosage. Compounds 11, 17, and 23 showed activity in both assays, and 23 also was active in the adjuvant-induced arthritis assay.

Synthesis and anti-inflammatory activity of 3-(benzylideneamino)coumarins in rodents.

A series of substituted 3-(benzylideneamino) coumarins was synthesized and evaluated for anti-inflammatory activity against carrageenan-induced edema in rats. Halogenated derivatives 4g and 4c, at oral doses of 100 mg/kg, showed 75 and 60% antiedmatous activity, respectively (phenylbutazone antiedematous activity, 58%). The analgesic activity of 4g and 4c, based on inhibition of acetic acid-induced writhing in mice (67 and 62%, respectively, at oral doses of 100 mg/kg) was comparable with that of aspirin (58%). However, these derivatives were devoid of antipyretic activity and showed low activity against adjuvant-induced arthritis.