Xanthones as potential antioxidants.

Xanthones (dibenzo-γ-pyrones) constitutes an important class of oxygenated heterocycles and occur as secondary metabolites in plants and microorganisms. They are known for various biological activities such as antioxidant, monoamine oxidase inhibitor, antihypertensive, hepatoprotective, antithrombotic, antifungal and anticancer. The tricyclic scaffold as well as the nature and/or position of the substituents present on it play an important role in displaying various biological activities. The unique structural scaffold and medicinal importance of xanthones have therefore attracted many Scientists in the past, to isolate or synthesize xanthones or their analogs as potential drug candidates. It would not be wrong to call them as close cousins to the polyphenol family that are known to possess strong antioxidant effects on the nervous system. The main two sources of xanthones are: Isolation from natural resources or synthesis. Though few reviews have been published in the past, mainly focusing on the anticancer activities of xanthone derivatives, but there is not a single review which is based on their antioxidant activities. We therefore have made efforts to briefly summarize natural and synthetic xanthones possessing antioxidant activity in this review.

Huge malignant melanoma of caruncle with extensive involvement of conjunctiva.

The caruncle is nodular structure lying at internal canthus medial to plica semilunaris. It is composed of elements of conjunctiva, cutaneous and lacrimal tissue. In spite of its diverse histopathology, lesions of caruncle are rare and malignant melanoma is further rarer. This tumour is potentially lethal, even after prompt and proper treatment, especially after delayed onset of therapy. Clinical metastases usually occur first to the lymph nodes in approximately 45% to 60% of patients with regional metastases. Eventually systemic dissemination may occur to lung, brain, liver, skin, bone and the gastrointestinal tract, although this often arises without prior clinical evidence of regional lymph node involvement. Here a rare case of huge malignant melanoma of caruncle with extensive involvement of plica semilunaris, fornix and palpebral conjuctiva in a 58-years old male is reported who was treated with local excision combined with cryotherapy and topical 0.02% mitomycin-C eye drops.

Fiber Bragg grating sensor for monitoring bone decalcification.

INTRODUCTION: Estimation of decalcification is a vital tool to discern bone health. Different techniques are used for its quantitative measurement, e.g. DEXA, QCT & QUS. All these techniques, although noninvasive, suffer from limitations such as radiation exposure and inaccurate values. Recently, fiber optic techniques are fast emerging for medical applications owing to their various attractive features like immunity to EMI/RFI, geometric versatility, chemical inertness, etc. MATERIAL AND METHODS: The effect of decalcification on strain response of a goat tibia was investigated in vitro using fiber Bragg grating (FBG) sensing technique. The bone was strained by using three-point bending technique and corresponding Bragg wavelength shifts were recorded. Two similar bone samples from the same animal were taken and one was partially decalcified. Strain response of decalcified and untreated bone was taken concurrently to monitor the effects of calcium loss and that of degradation with time. RESULTS AND CONCLUSION: The strain generated for same stress increased with greater degree of decalcification and a steep increase occurred after 2g calcium loss, indicating the onset of damage. The strain response, therefore gives a direct indication of the degree of calcium present in the bone. LEVEL OF EVIDENCE: Level III.

Safety evaluation of long term oral treatment of methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The manuscript is one of the series of attempts in authenticating scientific documentation of the seeds of Carica papaya being traditionally used for contraception. AIMS OF THE STUDY: To establish safety of the methanol sub-fraction (MSF) of the seeds of Carica papaya as a male contraceptive following long term oral treatment. MATERIALS AND METHODS: MSF was administered orally to albino rats at multiples of contraceptive dose (CD) at 50 (1x), 100 (2x), 250 (5x) and 500 (10x)mg/kg body weight daily for 52 weeks. Body weight, organs weight, morbidity, mortality, clinical chemistry, sperm analysis, histopathology and serum testosterone were evaluated to assess the safety and contraceptive efficacy. RESULTS: MSF treatment at various dose regimens, daily for 52 weeks did not show significant changes in body weight, organs weight, food and water intake and pre-terminal deaths compared to those of control animals. Sperm count and viability in 50mg/kg body weight treated animals and the weight of epididymis, seminal vesicle and prostate of all the treated animals showed significant reduction compared to control. Cauda epididymal spermatozoa of 50mg/kg body weight treated animals were immotile. Azoospermia was observed in 100, 250 and 500 mg/kg body weight treated animals. Serum clinical parameters, serum testosterone and histopathology of vital organs were comparable to those of control animals. Histology of testis revealed adverse effects on the process of spermatogenesis, while the histology of epididymis, seminal vesicles and ventral prostate showed no changes compared to control. CONCLUSION: The long term daily oral administration of MSF affects sperm parameters without adverse side effects and is clinically safe as a male contraceptive.

Antibacterial and Antifungal Potential of some Arid Zone Plants.

Sequential extracts of some medicinally important arid zone plants of Rajasthan, viz. Lepidagathis trinervis Nees., Polycarpea corymbosa Lam. and Sericostoma pauciflorum Stocks. ex Wight. were tested against six bacterial (Gram +ve and Gram -ve) and five fungal strains using agar well diffusion method. Ethyl acetate extract of L. trinervis showed maximum activity against Bacillus subtilis, Enterobactor aerogenes, Pseudomonas aeruginosa, Aspergillus flavus and Trichophyton rubrum (inhibition zone 16.00±0.81, 13.33±0.66, 14.33±1.85, 14.30±0.34 and 23.00±0.00 mm) at varied minimum inhibitory concentrations of 82, 20, 41, 41 and 20 µg/ml, respectively.

A postmarketing surveillance study of dexrabeprazole in the treatment of acid peptic disorders.

Dexrabeprazole [R(+) rabeprazole] is a novel proton-pump inhibitor which has recently become available in India for the treatment of acid peptic diseases. Experimental and clinical studies have shown superiority of dexrabeprazole (at half the recommended rabeprazole dose) over rabeprazole in terms of favourable pharmacokinetics, better efficacy and faster and greater healing activity. Results of present study in a large population of 4931 patients of acid peptic disorders, reconfirmed safety and efficacy of dexrabeprazole 10 mg once daily in the treatment of gastro-oesophageal reflux disease and also showed its effectiveness in the treatment of patients with peptic ulcers (gastric/duodenal).

Effect of non-zero Schottky barrier on the J-V characteristics of organic diodes.

Current-voltage (J-V) characteristics of poly(3-hexylthiophene) (P3HT) are studied at different temperatures upto high voltages approximately 20V in the hole-only device configuration. The characteristics are studied in the temperature range 310-210K. In the intermediate voltage range the J-V characteristics follow J proportional to V(l+1), where l > 1. As the voltage increases to high values J still varies as a power law i.e. as V(m), but contrary to the literature result m becomes < 2. This behavior is explained theoretically in terms of non-zero injection Schottky barriers. The complete analytical expressions for the actual trap filled limit voltage (V'(TFL)) and J-V curves beyond V'(TFL) are presented.

Diabetic retinopathy: a preventable scourge.

In recent years, the India has witnessed a rapidly exploding epidemic of diabetes mellitus. It would not be hyperbolic to state that diabetes mellitus is the mother of morbidity of all vital organs. Diabetic retinopathy and its complications cause considerable ocular morbidity as well. With effective management strategies visual loss due to the disease can be controlled and further dissemination of the disease could be prevented. The key to proper management of diabetic retinopathy includes prophylaxis by controlling blood sugar, periodical screening of retina for early detection, prompt referral for prevention of progression by appropriate laser photocoagulation, surgical correction of various anatomical abnormalities, low vision aids and rehabilitative measures in patients with severe visual loss. Howerver, the awareness level of visual consequences of this widely prevalent disease even amongst diabetics is lacking.

Estimation of naphthaquinones from Arnebia hispidissima (Lehm.) DC. In vivo and in vitro. I. Anti-inflammatory screening.

The hexane extract of Arnebia hispidissima yielded a mixture of naphthaquinones: arnebin-1, arnebin-7, tiglic acid (ester of dihydroxy alkannin), alkannin, arnebinol and cycloarnebin-7. To evaluate the anti-inflammatory activities of hexane extract and isolated naphthaquinones, models with carrageenan-induced acute arthritis and complete Freund's adjuvant (CFA)-induced chronic arthritis in rats were conducted. The observed results indicated that pretreatment with cycloarnebin-7 significantly inhibited the carrageenan-induced acute arthritis. Moreover, arnebin-1, significantly suppressed the development of chronic arthritis induced by CFA. The present study deals with the quantification of naphthaquinones from in vivo and in vitro cell cultures of plant species and isolated compounds from intact plant tested for their swelling inhibitory potency. It has been reported that arnebin-1 was the major naphthaquinone both in vivo (0.62%) and in vitro (0.27%) cell cultures.

Microsomal acetoxy drug: protein transacetylase of placenta: part 1. Characterization of DAMC: GST transacetylase.

We have earlier established in tissues of several mammalian animal species the existence of a novel membrane bound enzyme termed 7,8-diacetoxy-4-methylcoumarin (DAMC): protein transacetylase (TAase) that possibly transfers acetyl groups from the model acetoxy drug (DAMC) to certain enzyme protein viz. glutathione S-transferase (GST), cytochrome P-450 and NADPH cytochrome C reductase leading to the drastic modulation of their catalytic activities. We have in this report extended the studies to human tissue and characterized TAase from placenta. For this purpose placental microsomes were preincubated with DAMC along with the receptor protein (cytosolic GST) followed by the addition of the substrates of GST in order to quantify the catalytic activity of GST, the extent of inhibition of GST served as a measure of TAase. Placental TAase was also found to irreversibly activate NADPH cytochrome C reductase by DAMC. Placental enzyme activated the reductase even at very low concentration of DAMC. Iodoacetamide nearly abolished the placental TAase suggesting the presence of active thiol group in the enzyme and the TAase demonstrated hyperbolic kinetics. Kinetic constants obtained by varying the concentrations of either of the substrates DAMC or cytosolic GST characterized TAase catalysed reaction as the bimolecular reaction. Further studies are in progress to delineate the physiological importance of TAase in placenta.

Antimicrobial activity of triterpenoids from Heliotropium ellipticum.

Seven sterols and triterpenoids have been isolated from H. ellipticum and tested for their antimicrobial activity.

Lipase-catalyzed chemo- and enantioselective acetylation of 2-alkyl/aryl-3-hydroxypropiophenones.

The chemo- and enantioselective capabilities of porcine pancreatic lipase (PPL) in tetrahydrofuran, and Candida rugosa lipase (CRL) in diisopropyl ether have been investigated for the acetylation of racemic 2-alkyl/aryl-3-hydroxypropiophenones, which are important precursors in the synthesis of biologically active chromanones and isoflavanones. A highly chemoselective acetylation of primary hydroxy group in preference to phenolic hydroxy group leading to the formation of enantiomerically enriched monoacetates has been observed.

Radiation dose estimates in Indian adults in normal and pathological conditions due to 99Tcm-labelled radiopharmaceuticals.

ICRP Publications 53, 62 and 80 give organ dose coefficients and effective doses to ICRP Reference Man and Child from established nuclear medicine procedures. However, an average Indian adult differs significantly from the ICRP Reference Man as regards anatomical, physiological and metabolic characteristics, and is also considered to have different tissue weighting factors (called here risk factors). The masses of total body and most organs are significantly lower for the Indian adult than for his ICRP counterpart (e.g. body mass 52 and 70 kg respectively). Similarly, the risk factors are lower by 20-30% for 8 out of the 13 organs and 30-60% higher for 3 organs. In the present study, available anatomical data of Indians and their risk factors have been utilised to estimate the radiation doses from administration of commonly used 99Tcm-labelled radiopharmaceuticals under normal and certain pathological conditions. The following pathological conditions have been considered for phosphates/phosphonates--high bone uptake and severely impaired kidney function; IDA--parenchymal liver disease, occlusion of cystic duct, and occlusion of bile duct; DTPA--abnormal renal function; large colloids--early to intermediate diffuse parenchymal liver disease, intermediate to advanced parenchymal liver disease; small colloids--early to intermediate parenchymal liver disease, intermediate to advanced parenchymal liver disease; and MAG3--abnormal renal function, acute unilateral renal blockage. The estimated 'effective doses' to Indian adults are 14-21% greater than the ICRP value from administration of the same activity of radiopharmaceutical under normal physiological conditions based on anatomical considerations alone, because of the smaller organ masses for the Indian; for some pathological conditions the effective doses are 11-22% more. When tissue risk factors are considered in addition to anatomical considerations, the estimated effective doses are still found to be generally somewhat higher for the Indian, for both normal and pathological states (but lower than the values based on anatomical considerations alone). However, when the radiopharmaceutical is administered in quantities proportional to the body mass, the effective doses are 11-28% lower for the Indian under both normal and pathological conditions. It may be concluded that Indians are at a lower risk of radiation health detriment in comparison with the ICRP adult on administration of the various 99Tcm-labelled radiopharmaceuticals considered in this study.

Mechanism of biochemical action of substituted benzopyran-2-ones. Part 8: Acetoxycoumarin: protein transacetylase specificity for aromatic nuclear acetoxy groups in proximity to the oxygen heteroatom.

Our earlier work established a convenient assay procedure for acetoxycoumarin (AC): protein transacetylase (TA) by indirectly quantifying the activity of glutathione (GSH)-S-transferase (GST), the extent of inhibition of GST under the conditions of the assay represented TA activity. In this communication, we have probed the specificity for TA with respect to the number and position of acetoxy groups on the benzenoid as well as the pyranone rings of the coumarin system governing the efficient transfer of acetyl groups to the protein(s). For this purpose, coumarins bearing one acetoxy group, separately at C-3 or C-4 position and 4-methylcoumarins bearing single acetoxy group, separately at C-5, C-6 or C-7 position were synthesized and specificities to rat liver microsomal TA were examined. Negligible TA activity was discernible with 3-AC as the substrate, while the substrate efficiency of other AC were in the order 7-acetoxy-4-methylcoumarin (7 AMC)>6 AMC>5 AMC=5 ADMC=4 AC. To achieve a comparable level of GST inhibition which was proportional to the enzymatic transfer of acetyl groups to the protein (GST), the concentrations of 7-AMC, 6-AMC, 5-AMC and 4-AC were in the order 1:2:4:4, respectively. One diacetoxycoumarin, i.e., 7,8-diacetoxy-4-methylcoumarin (DAMC) was also examined and it was found to elicit maximum level of GST inhibition, nearly twice that observed with 7-AMC. These observations lead to the logical conclusion that a high degree of acetyl group transfer capability is conferred when the acetoxy group on the benzenoid ring of the coumarin system is in closer proximity to the oxygen heteroatom, i.e., when the acetoxy groups are at the C-7 and C-8 positions.

Prevalence of hepatitis viruses among multi-transfused homogenous thalassaemia patients.

Thalassaemic children being multi-transfused are at increased risk of parenterally transmissible hepatitis viruses and majority of them prone to develop chronic liver disease. The study is designed to find out the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) seromarkers and correlation of age, sex, number of transfusions and the viral aetiology in thalassaemics of central India. One hundred and four thalassaemic children were subjected to clinical, biochemical and serological analysis for the HBV, HCV and HDV viruses. The chi(2) test was applied to check the statistical significance of different variables. In the present study HBV markers were detected in 57 (56%) of the subjects while anti-HCV antibodies were observed in 21% of the patients. However, only four subjects were detected hepatitis B surface antigen (HBsAg) reactive but none of them were reactive for anti-HDV antibodies. Forty patients had raised alanine transaminase (ALT) levels and among them two were HBsAg reactive, 16 were anti-HBc antibody positive and 14 were anti-HCV reactive. The prevalence of hepatitis viruses and raised ALT levels are found to be significantly associated with the increasing age and number of blood units transfused to them. The present findings also document the excellent contribution of stringent screening of blood units and HBV vaccination programme for containing the HBV infection among thalassaemics.

Synthetic and biological activity evaluation studies on novel 1,3-diarylpropenones.

Fourteen novel C-prenylated and O-allylated 1,3-diarylpropenones (chalcones) were synthesized by Claisen-Schmidt condensation reaction of C-prenylated/O-allylated acetophenones with appropriate aldehydes; twelve of these model chalcones were screened in an assay based on the confrontation of invasive human MCF-7/6 mammary carcinoma cells with fragments of normal embryonic chick heart in vitro. Out of the twelve chalcones tested, three were found to exhibit potent anti-invasive activity. Some of these chalcones and their precursor acetophenones were also tested for inhibition of initiation of lipid peroxidation in rat liver microsomes; a prenylated acetophenone carrying two methoxy groups and two free phenolic hydroxy functions was found to be a potential antioxidant.

Chemoprevention of benzene-induced bone marrow and pulmonary genotoxicity.

Our earlier studies documented the ability of 7,8-diacetoxy-4-methylcoumarin (DAMC) to cause irreversible inhibition of cytochrome P-450 linked mixed function oxidases (MFO) mediated by membrane bound DAMC: protein transacetylase. Since P-450 catalyzed oxidation of benzene is crucial to its toxic effects, the action of DAMC and related analogues were considered promising in preventing the genotoxicity due to benzene. For this purpose rats were pretreated with various acetoxy-4-methylcoumarins (test compounds), which was followed by the administration of benzene either intratracheally (IT) or intraperitoneally (IP), and sacrificed 26 h after the injection of benzene. The incidence of micronuclei (MN) in bone marrow (BM) and lung (LG) were assessed by light and fluorescent microscopy, respectively. A dose-dependent induction of MN in BM and LG cells was observed in rats administered with benzene. A significant reduction in benzene-induced MN in BM and LG was observed as a result of DAMC administration to rats; a higher dose of DAMC resulted in greater inhibition of clastogenic action of benzene as revealed by MN incidence. 7,8-dihydroxy-4-methylcoumarin (DHMC), the deacetylated product of DAMC, demonstrated relatively lesser potency to inhibit the clastogenic action of benzene. This observation is consistent with the ability of DAMC to inhibit the formation of benzene oxide as well as to scavenge the oxygen radicals formed during the course of benzene metabolism. The fact that DHMC can only scavenge the oxygen radicals and is ineffective in inhibiting benzene oxidation in vivo explains the reduced capability of dihydroxy coumarin to prevent MN due to benzene. 7-Acetoxy-4-methylcoumarin (MAC) inhibits the MN due to benzene being roughly 50% of that produced by DAMC. DAMC is also effective in normalizing the cell cycle alterations produced by benzene in BM and LG. These observations further substantiate our hypothesis that the biological effects of acetoxy coumarins are mediated by the action of membrane bound transacetylase that catalyzes the acetylation of concerned proteins. Teratogenesis Carcinog. Mutagen. 21:181-187, 2001.

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 6: hydrolysis of 7,8-diacetoxy-4-methylcoumarin by a novel deacetylase in rat liver microsomes--a simple method for assay and characterisation.

The existence of a novel microsomal deacetylase in rat liver catalysing deacetylation of diacetoxy 4-methylcoumarins has been reported. A simple method is outlined for the enzyme assay based upon the quantification of the dihydroxy derivative by measuring the UV absorption of its complex with ADP and Fe3+ at 600 nm. The enzyme can be routinely assayed using 7,8-diacetoxy-4-methylcoumarin (DAMC) as the substrate and demonstrated hyperbolic kinetics and yielded Km and vmax values of 1250 microM and 500 units, respectively. The pH optima was found to be 7.5 for the enzyme. No DAMC deacetylase activity was found in hepatic cytosol and the enzyme activity was not discernible in extrahepatic tissues.

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 7: Assay and characterization of 7,8-diacetoxy-4-methylcoumarin:protein transacetylase from rat liver microsomes based on the irreversible inhibition of cytosolic glutathione S-transferase.

The enzymatic transfer of acetyl groups from acetylated xenobiotics to specific proteins is a relatively grey area in the evergreen field of biotransformation of foreign compounds. In this paper, we have documented evidence for the existence of a transacetylase in liver microsomes that catalyses the transfer of acetyl groups from 7,8-diacetoxy-4-methylcoumarin (DAMC) to glutathione S-transferase (GST), either purified or present in cytosol leading to the irreversible inhibition of GST. A simple procedure is described for the assay of transacetylase by preincubation of DAMC with liver microsomes and pure GST/liver cytosol, followed by the addition of 1-chloro-2,4-dinitrobenzene (CDNB) and reduced glutathione (GSH) in order to quantify GST activity by the conventional procedure. The extent of inhibition of GST by DAMC under the conditions of the assay is indicative of DAMC:protein transacetylase activity. Following the assay procedure described here, the transacetylase was shown to exhibit hyperbolic kinetics. The bimolecular nature of the transacetylase reaction was apparent by the demonstration of Km and vmax values. 7,8-Dihydroxy-4-methylcoumarin (DHMC), one of the products of transacetylase reaction was identified and quantified using the partially purified enzyme. The fact that p-hydroxymercuribenzoate (PHMB) and iodoacetamide abolished irreversible inhibition of GST upon the action of transacetylase on DAMC strongly characterized transacetylase as a protein containing thiol group at the active site. In addition, the relative specificities of acetoxy 4-methylcoumarins to transacetylase have been demonstrated.