The impact of antidepressant treatment on brain-derived neurotrophic factor level: An evidence-based approach through systematic review and meta-analysis.

OBJECTIVES: Antidepressant treatment alters brain-derived neurotrophic factor (BDNF) levels, but it is not well established whether BDNF can be used as a marker to prove the efficacy of antidepressant treatment. The present systematic review and meta-analysis aim at assessing the influence of antidepressant treatment on BDNF level and the Hamilton Depression Rating Scale (HDRS) score, thereby to establish the rationale of utilizing BDNF as a predictive biomarker and HDRS score as an indicator for antidepressant treatment efficacy. MATERIALS AND METHODS: Search was conducted in PubMed, Science Direct, and Cochrane databases using the key words "BDNF" and "Depression" and "Antidepressants." On the basis of the inclusion and exclusion criteria, studies were filtered and finally 6 randomized controlled trials were shortlisted. RESULTS: Comparison of serum BDNF level before and after antidepressant treatment was performed and the result showed that antidepressant treatment does not significantly affect the BDNF levels (confidence interval [CI]: -0.483 to 0.959; standard mean difference [SMD]: 0.238, P = 0.518). Egger's regression test (P = 0.455) and heterogeneity test (I2 = 88.909%) were done. Similarly, comparison of HDRS scores before and after antidepressant treatment indicated improvement in HDRS score suggesting positive outcome (CI: 1.719 to 3.707; SMD: 2.713, P < 0.001). Egger's regression test (P = 0.1417) and heterogeneity test (I2 = 89.843%) were performed. Publication bias was observed by funnel plot. CONCLUSION: Changes in BDNF levels do not occur uniformly for all the antidepressants. Hence, to use BDNF as a biomarker, it needs to be seen whether the same is true for all antidepressants.

Effect of human placental extract in the management of biofilm mediated drug resistance - A focus on wound management.

Management of infectious wounds, particularly chronic wounds and burn injuries, is a matter of global concern. Worldwide estimates reveal that, billions of dollars are being spent annually for the management of such chronic ailments. Evidently, bacterial biofilms pose a greater problem in the effective management of infection in chronic wounds, since most of the currently available antibiotics are unable to act on the microorganisms residing inside the protected environment of the biofilms. Accordingly, in the present study, we have attempted to evaluate the anti-biofilm properties of human placental extract (PLX) and also other virulence factors that are mediated via the quorum sensing (QS) signalling system. PLX is well known for its anti inflammatory action and it has been shown earlier some anti microbial and enzymatic activity also. PLX was found to produce significant inhibition of biofilm formation and also decreased the levels of pyoverdin and pyocyanin. The microscopic analysis (both light microscopy and atomic force microscopy) of biofilms was also used for substantiating the findings from spectrophotometric (crystal violet estimation) and fluorescence analysis (resazurin uptake). PLX pre-treatment decreased the hydrophobicity of gram-positive and gram negative cells, indicating the effect of placental extract on adherence property of planktonic cell, serving as an indicator for its antibiofilm effect on microorganisms. The reduced extracellular DNA (eDNA) content in biofilm matrix following treatment with PLX also indicates the effectiveness of placenta extract on bacterial adherence, which in turn serves as evidence substantiating the antibiofilm effects of the PLX. Furthermore, PLX was also found to be significantly effective in the in vitro wound biofilm model. Thus the present study, the first of its kind with PLX, establishes the therapeutic benefit of the same particularly in infected wounds, opening up newer avenue for further exploration.

Allylpyrocatechol Attenuates Collagen-Induced Arthritis via Attenuation of Oxidative Stress Secondary to Modulation of the MAPK, JAK/STAT, and Nrf2/HO-1 Pathways.

Rheumatoid arthritis (RA), an inflammatory autoimmune disorder, is characterized by synovial hyperplasia and bony destruction. The pathogenesis of RA includes redox dysregulation, concomitant with increased levels of proinflammatory mediators. As the ability of allylpyrocatechol (APC), a phytoconstituent of Piper betle leaves, to alleviate oxidative stress has been demonstrated in patients with RA, its antiarthritic activity was evaluated in an animal model of arthritis, and the underlying mechanism(s) of action clarified. The animal model was established by immunizing rats with bovine collagen type II (CII) followed by lipopolysaccharide, along with a booster dose of CII on day 15. Rats were treated with APC or methotrexate (MTX) from days 11 to 27, when paw edema, radiography, histopathology, and markers of inflammation were evaluated. The pro/antiinflammatory signaling pathways were studied in a RAW264.7 macrophage cell line. Allylpyrocatechol (APC) prevented the progression of arthritis as was evident from the reduction in paw edema, and attenuation of damage to bones and cartilage shown by radiography and histopathology. Additionally, there was reduction in the levels of proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] and restoration of the redox balance. Importantly, MTX ameliorated the features of arthritis but not the associated oxidative stress. In RAW264.7, APC inhibited generation of nitric oxide and proinflammatory cytokines (TNF-α, IL-6, and IL-12p40), and modulated the phosphorylation of proinflammatory (extracellular signal-regulated kinase 1/2, stress-activated protein kinase/c-Jun N-terminal protein kinase, and Janus kinase/signal transducers and activators of transcription) and cytoprotective (nuclear factor erythroid 2-related factor 2, heme oxygenase-1) signaling pathways. Taken together, APC controlled the development of arthritis, possibly via modulation of signaling pathways, and deserves further consideration as a therapy for RA.

Chemoprotective and chemosensitizing properties of selenium nanoparticle (Nano-Se) during adjuvant therapy with cyclophosphamide in tumor-bearing mice.

Cyclophosphamide (CP) is one of the widely used anticancer agents; however, it has serious deleterious effects on normal host cells due to its nonspecific action. The essential trace element Selenium (Se) is suggested to have chemopreventive and chemotherapeutic efficacy and currently used in pharmaceutical formulations. Previous report had shown Nano-Se could protect CP-induced hepatotoxicity and genotoxicity in normal Swiss albino mice; however, its role in cancer management is still not clear. The aim of present study is to investigate the chemoprotective efficacy of Nano-Se against CP-induced toxicity as well as its chemoenhancing capability when used along with CP in Swiss albino mice against Ehrlich's ascites carcinoma (EAC) cells. CP was administered (25 mg/kg b.w., i.p.) and Nano-Se was given (2 mg Se/kg b.w., p.o.) in concomitant and pretreatment schedule. Increase levels of serum hepatic marker, hepatic lipid peroxidation, DNA damage, and chromosomal aberration in CP-treated mice were significantly (P < 0.05) reversed by Nano-Se. The lowered status of various antioxidant enzymes in tumor-bearing mice after CP treatment was also effectively increased by Nano-Se. Administration of Nano-Se along with CP caused a significant reduction in tumor volume, packed cell volume, viable tumor cell count, and increased the survivability of the tumor-bearing hosts. The results suggest that Nano-Se exhibits significant antitumor and antioxidant effects in EAC-bearing mice. The potential for Nano-Se to ameliorate the CP-evoked toxicity as well as to improve the chemotherapeutic effect could have beneficial implications for patients undergoing chemotherapy with CP.

5,7-dihydroxy-2-(3-hydroxy-4, 5-dimethoxy-phenyl)-chromen-4-one-a flavone from Bruguiera gymnorrhiza displaying anti-inflammatory properties.

OBJECTIVE: Bruguiera gymnorrhiza (BRG) (L.) Lamk (Rhizophoraceae), a mangrove species, is widely distributed in the Pacific region, eastern Africa, Indian subcontinent, and subtropical Australia. The leaves of this plant are traditionally used for treating burns and inflammatory lesions. This study isolates the bioactive compound from the methanol extract of BRG leaves and evaluates the possible mechanisms of anti-inflammatory activity involved. MATERIALS AND METHODS: Bioassay-guided fractionation of BRG was performed to identify the bioactive fraction (displaying inhibition of cyclooxygenase 2 [COX2] - 5-lipoxygenase (5-LOX) activities and tumor necrosis factor-alpha (TNF-α) production at the tested concentrations of 100 and 10 µg/ml). The fractionation was performed by solvent extraction and preparative high-performance liquid chromatography. The bioactive compound was characterized by ultraviolet-visible, liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The antioxidant potential was evaluated by electron spin resonance spectrum of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical at 250 µM. The effect of the compound was also studied on TNF-α converting enzyme and nuclear factor kappa B (NF-κB) activities at the concentrations 100, 10 and 1 µg/ml. RESULTS: Bioassay-guided purification of BRG revealed the presence of a flavone (5,7-dihydroxy-2- [3-hydroxy-4,5-dimethoxy-phenyl]-chromen-4-one) of molecular weight 330Da. It demonstrated more than 80% inhibition against COX2, 5-LOX activities and TNF-α production at 100 µg/ml. It also displayed 40% inhibition against DPPH radical at the tested concentration along with 23.1% inhibition of NF-κB activity at 100 µg/ml. CONCLUSIONS: The isolated methoxy-flavone may play a predominant role in the anti-inflammatory properties displayed by BRG leaves. Such activity may involve multiple mechanisms, namely (a) modulation of oxidative stress (b) inhibition of arachidonic acid metabolism and (c) downregulation of pro-inflammatory cytokines probably through NF-κB inhibition.

In Vitro Metabolic Stability and Permeability of Gymnemagenin and Its In Vivo Pharmacokinetic Correlation in Rats - A Pilot Study.

Gymnema sylvestre is traditionally used for diabetes mellitus. A literature survey revealed very few reports, particularly on rat liver microsomal stability, caco-2 permeability and efflux concerns and its correlation with the bioavailability of gymnemagenin, an important component of G. sylvestre. Therefore, the objective of our study was to investigate the in vitro rat liver microsomal stability and caco-2 permeability along with the efflux of gymnemagenin and establish a probable correlation of these in vitro findings with pharmacokinetic parameters after oral and intravenous administration in rats.Rat liver microsomal stability studies to estimate the in vitro intrinsic half-life, clearance, and Caco-2 permeability after 21 days of culture to determine the apparent permeability from apical to basal and from basal to apical, and efflux ratio of gymnemagenin were performed using liquid chromatography-tandem mass spectrometry. A sensitive, robust bioanalytical method was validated and successfully applied to determine the plasma exposure of gymnemagenin. In vitro rat liver microsomal stability demonstrated that gymnemagenin metabolizes rapidly with a short apparent and intrinsic half-life (~ 7 min) and high intrinsic clearance, i.e., 190.08 µL/min/mg of microsomes. The results of the Caco-2 study indicated a poor permeability (1.31 × 10(- 6 )cm/sec) with a very high efflux ratio. The pharmacokinetic study revealed poor oral bioavailability (~ 14 %) of gymnemagenin and it was found to have a short half-life and a high clearance in rats. Our in vitro findings indicated low metabolic stability and poor Caco-2 permeability with high efflux, which might have a role in the observed poor oral bioavailability in rats.

Alteration of Zeta potential and membrane permeability in bacteria: a study with cationic agents.

In the present study, we have tried to establish the correlation between changes in Zeta potential with that of cell surface permeability using bacteria (Escherichia coli and Staphylococcus aureus). An effort has been made to establish Zeta potential as a possible marker for the assessment of membrane damage, with a scope for predicting alteration of cell viability. Cationic agents like, cetyl trimethyl ammonium bromide and polymyxin B were used for inducing alteration of Zeta potential, and the changes occurring in the membrane permeability were studied. In addition, assessment of poly-dispersity index (PDI), cell viability along with confocal microscopic analysis were performed. Based on our results, it can be suggested that alteration of Zeta potential may be correlated to the enhancement of membrane permeability and PDI, and it was observed that beyond a critical point, it leads to cell death (both Gram-positive and Gram-negative bacteria). The present findings can not only be used for studying membrane active molecules but also for understanding the surface potential versus permeability relationship.

Tricarbonyl (99m)Tc(i) and Re(i)-thiosemicarbazone complexes: synthesis, characterization and biological evaluation for targeting bacterial infection.

Methyl, ethyl and phenyl nitrofuryl thiosemicarbazone ligands (, and respectively) were radiolabeled with freshly prepared aqueous solution of a fac[(99m)Tc(CO)3(H2O)3](+) precursor. The radiochemical yield was around 98% as determined by thin layer chromatography and HPLC. The complexes exhibited substantial stability. The corresponding Re(i) complexes were prepared from a Re(CO)5Br precursor to understand the coordination behavior of the ligands against a tricarbonyl rhenium(i) precursor. The rhenium(i) complexes were characterized by means of IR, NMR and mass spectroscopic studies as well as by X-ray crystallography, and correlated with the technetium complexes by means of HPLC studies. Electrochemical reduction of monomeric Re(CO)3-complexes of nitrofuryl ethyl thiosemicarbazone was also studied using cyclic voltammetry. Biodistribution studies of (99m)Tc(CO)3-labeled thiosemicarbazones in rats intramuscularly infected with S. aureus exhibited substantial in vivo stability of the complex and moderate accumulation at the site of focal infection.

Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg(-1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

Antimicrobial properties of Kalanchoe blossfeldiana: a focus on drug resistance with particular reference to quorum sensing-mediated bacterial biofilm formation.

OBJECTIVES: This study attempts to investigate the antimicrobial properties of Kalanchoe blossfeldiana with a particular reference to quorum sensing (QS)-mediated biofilm formation. METHODS: The methanol extract of K. blossfeldiana leaves (MEKB) was evaluated for antimicrobial properties including QS-controlled production of biofilm (including virulence factor, motility and lactone formation) in Pseudomonas aeruginosa. Methanol extract of K. blossfeldiana was also evaluated for anti-cytokine (tumour necrosis factor-alpha, interleukin-6 and interleukin-1 beta) properties in peripheral blood mononuclear cells (PBMC). KEY FINDINGS: Methanol extract of K. blossfeldiana exhibited antimicrobial effect on clinical isolates, as well as standard reference strains. Pseudomonas aeruginosa exposed to MEKB (subminimum inhibitory concentration (MIC)) displayed reduced biofilm formation, whereas supra-MIC produced destruction of preformed biofilms. Methanol extract of K. blossfeldiana reduced the secretion of virulence factors (protease and pyoverdin) along with generation of acyl homoserine lactone (AHL). Confocal laser scanning microscopy images indicate reduction of biofilm thickness. The extract also reduced cytokine formation in lipopolysaccharide-stimulated PBMC. CONCLUSIONS: Kalanchoe blossfeldiana was found to interfere with AHL production, which in turn may be responsible for downregulating QS-mediated production of biofilm and virulence. This first report on the antibiofilm and anticytokine properties of this plant may open up new vistas for future exploration of this plant for combating biofilm-related resistant infections.

Medicinal plants, human health and biodiversity: a broad review.

Biodiversity contributes significantly towards human livelihood and development and thus plays a predominant role in the well being of the global population. According to WHO reports, around 80 % of the global population still relies on botanical drugs; today several medicines owe their origin to medicinal plants. Natural substances have long served as sources of therapeutic drugs, where drugs including digitalis (from foxglove), ergotamine (from contaminated rye), quinine (from cinchona), and salicylates (willow bark) can be cited as some classical examples.Drug discovery from natural sources involve a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Accordingly, medicinal-plant-based drug discovery still remains an important area, hitherto unexplored, where a systematic search may definitely provide important leads against various pharmacological targets.Ironically, the potential benefits of plant-based medicines have led to unscientific exploitation of the natural resources, a phenomenon that is being observed globally. This decline in biodiversity is largely the result of the rise in the global population, rapid and sometimes unplanned industrialization, indiscriminate deforestation, overexploitation of natural resources, pollution, and finally global climate change.Therefore, it is of utmost importance that plant biodiversity be preserved, to provide future structural diversity and lead compounds for the sustainable development of human civilization at large. This becomes even more important for developing nations, where well-planned bioprospecting coupled with nondestructive commercialization could help in the conservation of biodiversity, ultimately benefiting mankind in the long run.Based on these findings, the present review is an attempt to update our knowledge about the diverse therapeutic application of different plant products against various pharmacological targets including cancer, human brain, cardiovascular function, microbial infection, inflammation, pain, and many more.

Beverage-induced enhanced bioavailability of carbamazepine and its consequent effect on antiepileptic activity and toxicity.

The present study was undertaken to investigate the food-drug interaction of carbamazepine (CBZ). Common fruit juices [grapefruit juice (GFJ), lime juice (LJ)], known to inhibit the enzyme cytochrome P450 3A4 (CYP3A4), and some widely consumed beverages [milk (M), black tea (BT)] were involved in this study in the presence of CBZ, as might happen during clinical therapy. The effects of the beverages on the pharmacokinetics and drug-induced toxicity of CBZ was observed after concomitant administration for a period of 28 days. Accordingly, the influence of altered bioavailability of CBZ on its antiepileptic activity was investigated. A significant shift in the Cmax as well as Tmax of CBZ was observed in the presence of LJ and GFJ. This increase in bioavailability significantly enhanced hepatotoxicity and delayed the onset of tremor and piloerection against pentylene tetrazole (PTZ)-induced seizure in experimental animals. However, increased toxicity of CBZ was found to be absent with BT. Thus, from our observation, LJ or GFJ in the presence of CBZ significantly increased the bioavailability of CBZ, which might lead to increased toxicity and antiepileptic activity of the drug.

Curriculum for pharmacology in pharmacy institutions in India: opportunities and challenges.

The curriculum of pharmacy institutions in India is regulated by the All India Council for Technical Education (AICTE) and the Pharmacy Council of India (PCI) at degree and diploma levels. However, it has been over two decades that the syllabi have been revised by these regulatory agencies. Considering the dynamic character of pharmacology, it is essential to prepare a syllabus that caters to the contemporary needs of the academic institutions and pharmaceutical industry, the community. Pharmacists are also witnessing a greater role in community pharmacy practice as well as in several healthcare sectors. Considering these facts, a panel discussion was held at IPSCON 2013, (the Annual Conference of Indian Pharmacological Society) at Bangalore. The discussion saw several recommendations for syllabi for institutions offering various pharmacy courses to meet the objectives of teaching, learning and research in Pharmacology. This article documents a summary of the discussion. For B. Pharm. course, a balance between industry-oriented pharmacology and clinical pharmacy has been recommended. Redundant animal experiments should be replaced with the simulation experiments or those which are feasible in the light of stringent regulations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). It is recommended that the M. Pharm curriculum should focus on preclinical research with the inclusion of molecular biology and experiments on gene expression, proteomics, pharmacogenomics, cell culture and tissue culture. In general, at all levels, exposure of students to hospitals and clinicians is needed. Pharm. D., syllabus too should lay lesser emphasis on experimental pharmacology. Present experiments in the D. Pharm. course have no relevance to the program objectives and hence, only experiments through demonstrations or simulated preparations or interactive videos maybe undertaken. Regulatory bodies as well as universities should design a comprehensive syllabus and plan an effective pedagogy to prepare graduates who are competent and capable of bringing positive changes in the community and healthcare in India.

Anti-biofilm activity of Marula - a study with the standardized bark extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Marula (Sclerocarya birrea; family - Anacardiaceae) is an African plant, which enjoys wide socio-economic importance particularly in southern part of Africa. The fruits are consumed as food and also as alcoholic beverage (cream liquor). In different parts of Africa, the decoction of the bark is traditionally used for the treatment of dysentery, diarrhoea, and various other infectious conditions. The aim of the study was to investigate the anti-biofilm properties of the methanol extract of Marula bark (stem bark of Sclerocarya birrea), with a view towards combating the emergence of antimicrobial resistance often associated with bacterial biofilms. MATERIALS AND METHODS: The standardized methanol extract was initially tested for its antimicrobial property. The crystal violet assay was used for evaluating anti-biofilm (biofilm formation by Pseudomonas aeuginosa) activity. Further in order to study the mechanism of anti-biofilm activity, the same was evaluated for understanding its role on various quorums sensing mediated phenomenon (swarming motility assay, protease and pyoverdin assay) that are known to be associated with the formation of biofilms and pathogenicity. RESULTS: The methanol extract showed no inhibition of bacterial growth up to a concentration of 200 µg/ml. Interestingly, the sample produced anti-biofilm activity (around 75% decrease; 100 µg/ml) at sub-lethal concentration. Further it also significantly reduced the QS mediated swarming motility. The release of various virulent factors (protease and pyoverdin) was found to be lowered when pre-treated with the extract. CONCLUSION: The present study illustrates the anti-biofilm property Sclerocarya birrea. The standardized extract significantly disrupted the quorum sensing mediated production of biofilm formation and also inhibited swarming ability of the cells. The extract displayed a regulatory role on the secretion of protease and pyoverdin, two QS dependent pathogenic factors found in Pseudomonas aeruginosa. This study also validates the ethnobotanical use of Marula.

Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC-MS/MS method.

CONTEXT: Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is widely used in tribal medicine in India and some other countries for multiple clinical applications. It contains andrographolide (AG) (diterpenoid lactone), a major phytomarker which probably accounts for its medicinal properties. OBJECTIVE: This study investigates the site-specific distribution of AG in different tissues of rats and its pharmacokinetic parameter evaluation by using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. MATERIALS AND METHODS: A simple and sensitive LC-MS/MS method has been developed and validated to quantify the presence of AG in plasma and various tissues of rat following oral administration of A. paniculata extract and AG in a dose of 133.33 and 100 mg/kg/day, respectively, for four weeks. RESULTS: The present study showed that the highest concentration of AG was in kidney (156.12 ng/g) followed by liver, spleen and brain while almost same concentration was found in heart and lung. The apparent C(max), T(max), elimination half-life and total exposure (AUC(0-α)) were 115.81 ng/ml, 0.75, 2.45 and 278.44 ngh/ml, respectively. CONCLUSION: This was an attempt to determine the presence of AG (a known biomarker) in tissues such as kidney, heart, lungs, brain and plasma of rats using a validated LC-MS/MS method. Furthermore, the observed reduced concentration in plasma and various tissues from 1 to 8 h might be attributed to relatively rapid elimination or distribution of AG from the central compartment.

Arylamine N-acetyl Transferase (NAT) in the blue secretion of Telescopium telescopium: xenobiotic metabolizing enzyme as a biomarker for detection of environmental pollution.

Telescopium telescopium, a marine mollusc collected from Sundarban mangrove, belongs to the largest mollusca phylum in the world and exudes a blue secretion when stimulated mechanically. The blue secretion was found to metabolize (preferentially) para-amino benzoic acid, a substrate for N-acetyl transferase (NAT), thereby indicating acetyl transferase like activity of the secretion. Attempts were also made to characterise bioactive fraction of the blue secretion and to further use this as a biomarker for monitoring of marine pollution. NAT like enzyme from marine mollusc is a potential candidate for detoxification of different harmful chemicals. A partially purified extract of blue secretion was obtained by fractional precipitation with (NH4)2SO4. From different fractions obtained by precipitation, the 0-30% fraction (30S) displayed NAT like activity (using para amino benzoic acid as a substrate with para nitrophenyl phosphate or acetyl coenzyme A as acetyl group donors). Maximum NAT like enzyme activity was attained at 25°C and at a pH of 6. The enzyme activity was found to be inhibited by 5 mM phenyl methyl sulfonyl fluoride. The divalent metal ions reduced NAT like activity of 30S. Moreover, Cu(2+) and Zn(2+) (at concentration of 1 mM) completely inhibited NAT activity. The thermal stability and bench-top stability studies were performed and it was found that the enzyme was stable at room temperature for more than 24 hours. Results from the present study further indicate that heavy metal content in blue secretion gradually decreased from pre-monsoon to post-monsoon season, which also corresponded to the change in NAT like activity. Therefore, this article stresses the importance of biomarker research for monitoring pollution.

Pharmacological studies on Buchanania lanzan Spreng.- a focus on wound healing with particular reference to anti-biofilm properties.

OBJECTIVE: To evaluate the wound healing activity of the methanolic root extract of Buchanania lanzan Spreng. (B. lanzan), with a focus on antimicrobial and anti-biofilm properties. METHODS: The extract was evaluated for its wound healing properties (excision and incision models) as evident from the analysis of tensile strength and wound contraction. The extract was also screened for antibacterial properties against different Gram positive and Gram negative bacterial strains. B. lanzan was also studied for its effect on biofilm formation and disruption of preformed biofilms. The synergistic effect of B. lanzan was determined in combination with gentamicin. RESULTS: Topical application of B. lanzan (10% w/w ointment) significantly increased (40.84%) the tensile strength in the incision wound model. B. lanzan also showed significant wound healing activity in excision model and such significant activity was observed from the 9th day. Whereas Soframycin displayed significant wound healing activity from the 6th day. It was found that root extracts of B. lanzan revealed significant inhibition against all tested pathogens. B. lanzan displayed antimicrobial activity against Gram positive (MIC 0.625 mg/mL) and Gram negative (MIC 0.625-1.25 mg/mL). B. lanzan was able to reduce biofilm formation and also caused disruption of preformed biofilms in a manner similar to ciprofloxacin. However, gentamicin was found to be ineffective against biofilms formed by Gram negative organism. According to the fractional inhibitory concentration index, B. lanzan displayed synergistic activity when it was combined with gentamicin. CONCLUSIONS: From this study it may be concluded that the root extract of B. lanzan revealed significant wound healing potential, which was supported and well correlated with pronounced antibacterial activity of the tested plant parts.

Tricarbonyltechnetium(I) and tricarbonylrhenium(I) complexes of amino acids: crystal and molecular structure of a novel cyclic dimeric Re(CO)3-amino acid complex comprised of the OON donor atom set of the tridentate ligand.

Radiolabeled complexes of monoamino polycarboxylic, polyamino monocarboxylic and thiol containing amino acid ligands were prepared from a fac-[(99m)Tc(CO)3(H2O)3](+) precursor.The overall radiochemical yield was 94-98%. The complexes exhibited substantial in vitro and in vivo stability. The corresponding Re(I) complexes of the ligands DAPA, Asp and CysH were prepared and characterized by means of IR, NMR, and MS spectroscopic studies, as well as X-ray crystallography (for those containing D,L-DAPA and D,L-Asp). The rhenium complexes have been structurally correlated with the technetium complexes by means of HPLC studies. The reaction of Re(CO)5Cl with D,L-Asp in presence of triethylamine led to the formation of a new class of cyclic dimeric complexes formed by the OON donor atom set of the tridentate ligands. The amino carboxylate ligand system formed well defined complexes with a fac-[M(CO)3(H2O)3](+) core and shows good promise in (99m)Tc(CO)3 tracer development.

Hypokalemia: a potent risk for QTc prolongation in clarithromycin treated rats.

Clarithromycin belongs to macrolide group of antibiotics commonly known for their proarrhythmic potency. Besides agents interfering with CYP 3A, electrolyte imbalance might influence repolarization problems of clarithromycin. The proarrhythmic tendency of clarithromycin particularly in association with hypokalemia manifested a change in QT interval in rat electrocardiogram (ECG). Varying degree of hypokalemia was induced by intraperitoneal injection of furosemide (50, 30, and 10 mg/kg, for seven days). The serum electrolyte levels confirmed that hypokalemia was established in the groups receiving furosemide. Simultaneously, clarithromycin was orally administered in the doses of 100 and 80 mg/kg for seven days. ECG was measured for 5 min in anaesthetised rat before and after 2 h of treatment. The QT interval was corrected for heart rate and reported as corrected QT (QTc). Distinct QTc interval prolongation was observed in groups receiving furosemide (50 and 30 mg/kg) alone and in all the groups receiving clarithromycin alongside furosemide. Neither, clarithromycin (80 mg/kg) nor furosemide (10 mg/kg) exhibited any significant change in the QTc interval but in combination these drugs led to a significant increase in the QTc interval. Most interestingly, potassium supplementation was found to reduce QTc interval in the group presenting with maximum QTc prolongation. These results suggest that hypokalemic condition potentiates the clarithromycin induced QTc prolongation, thereby indicating the importance of monitoring serum electrolyte during clarithromycin therapy. Although, selection of rat for examination of proarrhythmic liability is controversial, this report may be considered as an evidence of hypokalemia potentiating clarithromycin induced QTc prolongation.

Evaluation of (99m)Tc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection.

The aim of this study was to develop (99m)Tc(CO)(3)-labeled fluoroquinolones as novel SPECT radiopharmaceuticals for imaging bacterial infection. Fluoroquinolones, e.g., ofloxacin (OFX), levofloxacin (LVX), lomefloxacin (LMX) and norfloxacin (NFX) were labeled with a fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor. The radiochemical purity of the radiopharmaceuticals exceeded 97% as determined by thin layer chromatography and HPLC. No further purification was necessary before injection. The Re(CO)(3) complex of one of the fluoroquinolones (levofloxacin) was synthesized using [Re(CO)(3)(H(2)O)(3)]OTf and Re(CO)(5)Br precursors in separate experiments and characterized by IR, NMR and mass spectroscopic analysis. These studies revealed the formation of a single species in which the piperazinyl nitrogen and the -COOH group attached to the benzoxazine ring system of quinolone were involved in co-ordination to the Re(CO)(3) core. The HPLC elution pattern and retention time of the Re(CO)(3)-LVX complex were comparable to those of the corresponding (99m)Tc(CO)(3)-complex proving their similarity. When incubated in isotonic saline and serum up to 24 h (99m)Tc(CO)(3)-labeled fluoroquinolones exhibited good in vitro stability. Biodistribution studies performed at different time points on rats intramuscularly infected with S. aureus as well as on rats with sterile inflammation revealed a higher uptake in the infected area than the turpentine induced inflamed area. The uptake in infected thigh was significant with (99m)Tc(CO)(3)-OFX followed by (99m)Tc(CO)(3)-LVX. The mean ratios of the uptake in infected/non-infected thighs were 4.75 and 4.27 at 8 h and 24 h, respectively, for (99m)Tc(CO)(3)-OFX and 4.42 and 4.18 at 24 h and 8 h, respectively, for (99m)Tc(CO)(3)-LVX. The above abscess to muscle ratios were higher than reported for (99m)Tc-ciprofloxacin and other (99m)Tc-labeled fluoroquinolones. Scintigraphy studies also showed a significant uptake in the infectious lesions suggesting that (99m)Tc(CO)(3)-fluoroquinolones might be useful as diagnostic agents for targeted delivery in bacterial infection.