BIOCHEMICAL PHARMACOLOGY

Ethanolic extracts of Mimosa pudica leaves were screened for phytochemical constituents and antimicrobial activity towards
pathogens i.e. bacteria and fungi. The activity was tested against Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella
pneumonia, Aspergillus flavus and Trycophyton rubrum at different concentrations of 25, 50, 75 and 100 μl/ disc and the results
have been illustrated. Phytochemical analysis of the extract revealed that the antimicrobial activity of the plant materials is due
to the presence of active constituents like alkaloids or tannins.
Key words: Mimosa pudica, antimicrobial activity, phytochemical.

A photometric method for determining acetylcholinesterase activity of tissue extracts, homogenates, cell suspensions, etc., has been described. The enzyme activity is measured by following the increase of yellow color produced from thiocholine when it reacts with dithiobisnitrobenzoate ion. It is based on coupling of these reactions:

The mechanisms responsible for the antiproliferative and cytotoxic effects of the anthracycline antibiotics doxorubicin (Adriamycin ® ) and daunorubicin (daunomycin) have been the subject of considerable controversy. This commentary addresses the potential role of DNA synthesis inhibition, free radical formation and lipid peroxidation, DNA binding and alkylation, DNA cross-linking, interference with DNA strand separation and helicase activity, direct membrane effects, and the initiation of DNA damage via the inhibition of topoisomerase II in the interaction of these drugs with the tumor cell. One premise underlying this analysis is that only studies utilizing drug concentrations that reflect the plasma levels in the patient after either bolus administration or continuous infusion are considered to reflect the basis for drug action in the clinic. The role of free radicals in anthracycline cardiotoxicity is also discussed.

The monoamine hypothesis has been the prevailing hypothesis of depression over the last several decades. It states that depression is associated with reduced monoamine function. Hence efforts to increase monoamine transmission by inhibiting serotonin (5-HT) and norepinephrine (NE) transporters has been a central theme in depression research since the 1960s. The selective 5-HT reuptake inhibitors (SSRIs) and 5-HT and NE reuptake inhibitors (SNRIs) that have emerged from this line of research are currently first line treatment options for major depressive disorder (MDD). One of the recent trends in antidepressant research has been to refine monoaminergic mechanisms by targeting monoaminergic receptors and additional transporters (e.g. with multimodal drugs and triple re-uptake inhibitors) or by adding atypical antipsychotics to SSRI or SNRI treatment. In addition, several other hypotheses of depression have been brought forward in pre-clinical and clinical research based on biological...

b i o c h e m i c a l p h a r m a c o l o g y 7 4 ( 2 0 0 7 ) 8 3 1 -8 4 0 GTPase Cell division a b s t r a c t Cinnamaldehyde is a natural product from spices that inhibits cell separation in Bacillus cereus. Cell division is regulated by FtsZ, a prokaryotic homolog of tubulin. FtsZ assembles into the Z-ring at the site of cell division. Here, we report the effect of cinnamaldehyde on FtsZ and hence on the cell division apparatus. Cinnamaldehyde decreases the in vitro assembly reaction and bundling of FtsZ. It is found that cinnamaldehyde perturbs the Zring morphology in vivo and reduces the frequency of the Z ring per unit cell length of Escherichia coli. In addition, GTP dependent FtsZ polymerization is inhibited by cinnamaldehyde. Cinnamaldehyde inhibits the rate of GTP hydrolysis and binds FtsZ with an affinity constant of 1.0 AE 0.2 mM À1 . Isothermal titration calorimetry reveals that binding of cinnamaldehyde to FtsZ is driven by favorable enthalpic interactions. Further, we map the cinnamaldehyde binding region of FtsZ, using the saturation transfer difference-nuclear magnetic resonance and an in silico docking model. Both predict the cinnamaldehyde binding pocket at the C terminal region involving the T7 loop of FtsZ. Our results show that cinnamaldehyde binds FtsZ, perturbs the cytokinetic Z-ring formation and inhibits its assembly dynamics. This suggests that cinnamaldehyde, a small molecule of plant origin, is a potential lead compound that can be developed as an anti-FtsZ agent towards drug design. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / b i o c h e m p h a r m

The plant-derived phenolic compounds gossypol, quercetin and myricetin are powerful inhibitors of iron-induced lipid peroxidation in rat liver microsomes, under all five experimental conditions tested and at low micromolar concentrations (ICjo < 1.5 yM). However, they greatly accelerate the generation of hydroxyl radicals (*OH) from H,O, in the presence of Fe'+-EDTA at pH7.4, as measured by the deoxyribose assay. At 100 PM, the three phenolic compounds enhanced *OH formation up to eight-fold. The hydroxyi radical generation was inhibited by catalase and superoxide dismutase, suggesting a mechanism in which the phenols oxidize to produce superoxide radical, which then assists *OH generation from HzO, in the presence of Fe '+-EDTA. At concentrations up to 75 PM, quercetin and myricetin also accelerate bleomycin-dependent DNA damage in the presence of Fe3+, possibly by reducing the Fe 3+-bleomycin-DNA complex to the Fe 2t form. Hence these naturally-occurring substances can have nro-oxidant effects under some reaction conditions and cannot be classified simplistically as "antioxidants".

To discover safe and effective topical skin-lightening agents, we have evaluated alkyl esters of the natural product gentisic acid (GA), which is related to our lead compound methyl gentisate (MG), and four putative tyrosinase inhibitors, utilizing mammalian melanocyte cell cultures and cell-free extracts. Desirable characteristics include the ability to inhibit melanogenesis in cells (IC 50 Ͻ 100 g/mL) without cytotoxicity, preferably due to tyrosinase inhibition. Of the six esters synthesized, the smaller esters (e.g. methyl and ethyl) were more effective enzyme inhibitors (IC 50 ϳ 11 and 20 g/mL, respectively). For comparison, hydroquinone (HQ), a commercial skin "bleaching" agent, was a less effective enzyme inhibitor (IC 50 ϳ 72 g/mL), and was highly cytotoxic to melanocytes in vitro at concentrations substantially lower than the IC 50 for enzymatic inhibition. Kojic acid was a potent inhibitor of the mammalian enzyme (IC 50 ϳ 6 g/mL), but did not reduce pigmentation in cells. Both arbutin and magnesium ascorbyl phosphate were ineffective in the cell-free and cell-based assays. MG at 100 g/mL exhibited a minimal inhibitory effect on DHICA oxidase (TRP-1) and no effect on DOPAchrome tautomerase (TRP-2), suggesting that MG inhibits melanogenesis primarily via tyrosinase inhibition. MG and GA were non-mutagenic at the hprt locus in V79 Chinese hamster cells, whereas HQ was highly mutagenic and cytotoxic. The properties of MG in vitro, including (1) pigmentation inhibition in melanocytes, (2) tyrosinase inhibition and selectivity, (3) reduced cytotoxicity relative to HQ, and (4) lack of mutagenic potential in mammalian cells, establish MG as a superior candidate skin-lightening agent.

Objective structured practical examination (OSPE) a new
assessment tool has been implemented in a few medical colleges.
This method of assessment was planned to be implemented in our
medical college, before which the authors planned to compare the
scores obtained by the students by conventional method of
examination and OSPE. The marks obtained by the two methods
of examination were compared and a feedback was collected from
students to study their perspective towards OSPE. There was
statistically significant difference in the mean of the scores
obtained by conventional method and that of OSPE. The students’
perception about OSPE was good. This study enabled the authors
to standardize the pattern of OSPE and implement it.

In the immature mammalian brain during a period of rapid growth (brain growth spurt/synaptogenesis period), neuronal apoptosis can be triggered by the transient blockade of glutamate N-methyl-d-aspartate (NMDA) receptors, or the excessive activation of ␥-aminobutyric acid (GABA A ) receptors. Apoptogenic agents include anesthetics (ketamine, nitrous oxide, isoflurane, propofol, halothane), anticonvulsants (benzodiazepines, barbiturates), and drugs of abuse (phencyclidine, ketamine, ethanol). In humans, the brain growth spurt period starts in the sixth month of pregnancy and extends to the third year after birth. Ethanol, which has both NMDA antagonist and GABA A agonist properties, is particularly effective in triggering widespread apoptotic neurodegeneration during this vulnerable period. Thus, maternal ingestion of ethanol during the third trimester of pregnancy can readily explain the dysmorphogenic changes in the fetal brain and consequent neurobehavioral disturbances that characterize the human fetal alcohol syndrome. In addition, there is basis for concern that agents used in pediatric and obstetrical medicine for purposes of sedation, anesthesia, and seizure management may cause apoptotic neuronal death in the developing human brain.

Rndioactivitv from "C-mctronidnzolc was quickly taken from the medium into cells of 'Ci~lw~~wutrs rcc~;irurli.s. It was rapidly metabolised by these organisms. largely to one product. bq removal of the S-nitro group. Radioactivity from "C-metronidaLolc was also bound lo DNA and protein of 7: ruyirwlis but not to RNA. Inhibition of nucleic acid synthesis was domonstrntcd in both this and other drug-sensitive organisms at drug concontrations as low as I jrg:ml. A possible mechanism of action of the drug has been postu-Iatcd.

Extensive research within the last two decades has revealed that most chronic illnesses, including cancer, diabetes, and cardiovascular and pulmonary diseases, are mediated through chronic inflammation. Thus, suppressing chronic inflammation has the potential to delay, prevent, and even treat various chronic diseases, including cancer. Various nutraceuticals from fruits, vegetables, vitamins, spices, legumes, and traditional Chinese and Ayurvedic medicine have been shown to safely suppress proinflammatory pathways; however, their low bioavailability in vivo limits their use in preventing and treating cancer. We describe here the potential of nanotechnology to fill this gap. Several nutraceuticals, including curcumin, green tea polyphenols, coenzyme Q, quercetin, thymoquinone and others, have been packaged as nanoparticles and proven to be useful in "nano-chemoprevention" and "nano-chemotherapy."

A B S T R A C T Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by destruction of the articular cartilage, subchondral bone alterations and synovitis. Current treatments are focused on symptomatic relief but they lack efficacy to control the progression of this disease which is a leading cause of disability. Therefore, the development of effective disease-modifying drugs is urgently needed. Different initiatives are in progress to define the molecular mechanisms involved in the initiation and progression of OA. These studies support the therapeutic potential of pathways relevant in joint metabolism such as Wnt/ b-catenin, discoidin domain receptor 2 or proteinase-activated receptor 2. The dysregulation in cartilage catabolism and subchondral bone remodeling could be improved by selective inhibitors of matrix metalloproteinases, aggrecanases and other proteases. Another approach would favor the activity of anabolic processes by using growth factors or regulatory molecules. Recent studies have also revealed the role of oxidative stress and synovitis in the progression of this disease, supporting the development of a number of inhibitory strategies. Novel targets in OA are represented by genes involved in OA pathophysiology discovered using gene network, epigenetic and microRNA approaches. Further insights into the molecular mechanisms involved in OA initiation and progression may lead to the development of new therapies able to control joint destruction and repair.

Tricyclic antidepressants have been reported to have an depressants exists in animals, due to the fact that different analgesic effect (1,2] and some of them have been suc-methods were used to measure pain , nor is the mechcessfully used to alleviate chronic pain in man [3-61. It is anism through which antidepressants exert their analgesic not, however, clear whether the analgetic effect of anti-effects known . We wish to report evidence for a direct

DNA methylation and chromatin structure patterns are tightly linked components of the epigenome, which regulate gene expression programming. Two contradictory changes in DNA methylation patterns are observed in breast cancer; regional hypermethylation of specific genes and global hypomethylation. It is proposed here that independent mechanisms are responsible for these alterations in DNA methylation patterns and that these alterations deregulate two different processes in breast cancer. Regional hypermethylation is brought about by specific regional changes in chromatin structure, whereas global demethylation is caused by a general increase in demethylation activity. Hypermethylation silences growth regulatory genes resulting in uncontrolled growth whereas hypomethylation leads to activation of genes required for metastasis. DNA methylation inhibitors activate silenced tumor suppressor genes resulting in arrest of tumor growth and are now being tested as candidate anticancer drugs. Demethylation inhibitors are proposed here to be potential novel candidate antimetastatic agents, which would bring about methylation and silencing of metastatic genes. Future therapeutic application of either methylation or demethylation inhibitors in cancer therapy would require understanding of the relative role of these processes in the evolution of cancer. #

Angiotensin converting enzyme (ACE) activity was evaluated in the presence of flavanol-rich foods, i.e., wines, chocolates, and teas, and of purified flavonoids. All foods assayed inhibited ACE activity, red wines being more effective than white wine, and green tea more effective than black tea. The inhibition of ACE activity was associated with both phenolic and flavanol content in the foods. When isolated polyphenols were assayed, procyanidins (dimer and hexamer) and epigallocatechin significantly inhibited enzyme activity; similar concentrations of (+)-catechin, (-)-epicatechin, gallic acid, chlorogenic acid, caffeic acid, quercetin, kaempferol, and resveratrol were ineffective. When ACE activity was assayed in rat kidney membranes in the presence of chocolate extracts or purified procyanidins, it was observed that the inhibition depended on the chocolate content of flavanols and the number of flavanol units constituting the procyanidin. These experiments demonstrate that flavanols either isolated or present in foods could inhibit ACE activity. The occurrence of such inhibition in vivo needs to be determined, although is supported by the association between the consumption of flavanolrich foods and reductions in blood pressure observed in several experimental models.

Polymethoxylated flavones and C-glycosyl derivatives isolated from medicinal plants besides other flavonoid compounds were studied for their influence on lipid peroxidation induced by FeSO,+cysteine in rat liver microsomes. A number of hydroxytlavones (e.g. luteolin); C-glycosylflavones (e.g. orientin); methoxyflavones (e.g. gardenin D) and flavonols (e.g. datiscetin), as well as the flavanol leucocyanidol and the biflavone amentoflavone behaved as inhibitors of non-enzymic lipid peroxidation. Structure-activity relationships were established and it was observed that the structural features for active polyhydroxylated compounds were different from those of polymethoxylated flavones, antiperoxidative flavonoids possessing a high lipophilicity.

ÖZET Malignant hipertermi (MH) yayg n olmayan, ya am tehdit edici, iskelet kas hücrelerinin akut farmokogenetik hastal d r. Halojenli gaz anestetiklerine ve depolarize edici kas gev eticilerine maruz kalan hipermetabolik cevap olu turma e ilimi olan ki ilerde görülür. Krizin patofizyolojisinde, sarkoplazmik retikulumdan kontrolsüz biçimde sitoplazmik serbest kalsiyumun sal nmas ve böylece enerji üretici biyokimyasal reaksiyonlar n aktive edilmesi vard r. Yüksek ate , hiperkalemi ve asidozis sonucu organ sistem yetmezli i ve rabdomyolizis olu abilir. Sarkoplazmik retikulumunun kalsiyum sal c kanal olan ryanodin reseptörü, malignant hipertermi e iliminin ana belirleyicisidir. Ryanodin reseptör geninde olu abilecek birden fazla mutasyonlar buna neden olabilir. Di er genlerde olu abilecek mutasyonlar da böyle bir sonuç do urabilir. Klasik ani krizin bulgular yüksek Et-CO2 (end-tidal: Et), iskelet kas kat l , ta ikardi, hipertermi ve asidozistir. E er sendrom te his edilemez ve zaman nda müdahalede edilmez ise, ölüm oran yakla k %70'e kadar yükselebilmektedir. Triger ajan n uygulanmas n n hemen kesilmesi, oksijenasyon, asidozisin ve elektrolit bozuklu unun düzeltilmesi, hastan n so utulmas ve dantrolen uygulanmas , sendrom tedavisinin ana basamaklar d r. Anahtar kelimeler: Malignant hipertermi, ryanodin reseptörü, halothan, kafein, kalsiyum iyonu, dantrolen, in vitro kas lma testi. SUMMARY Malignant hyperthermia (MH) is an uncommon, lifethreatening, acute pharmacogenetic disorder of the skeletal muscle cell. It is appeared in susceptible individuals as a hypermetabolic response on exposure to halogenated volatile anaesthetics and depolarizing muscle relaxants. There may also be a relationship between susceptibility to MH, heat stroke and exercise-induced rhabdomyolysis. The pathophysiology of the crisis involves an uncontrolled release of cytoplasmic free calcium from the sarcoplasmic reticulum leading to activation of energyproducing biochemical pathways. Organ system failure and rhabdomyolysis may occur as a result of high fever, hyperkalaemia and acidosis. The ryanodine receptor, the calciumrelease channel of the sarcoplasmic reticulum, is the primary locus for malignant hypothermia susceptibility. Multiple mutations in the gene for the ryanodine receptor protein are causative. Other genes may also be involved.

Resveratrol (trans-3,4 0 ,5-trihydroxystilbene), a naturally occurring hydroxystilbene, is considered an essential antioxidative constituent of red wine possessing chemopreventive properties. However, resveratrol and even more its metabolite piceatannol were reported to have also cytostatic activities. In order to find out whether this is related to antioxidative properties of those compounds, we synthesized five other polyhydroxylated resveratrol analogues and studied structure-activity relationships between pro-/antioxidant properties and cytotoxicity. Radical scavenging experiments with O 2 À (5,5-dimethyl-1-pyrroline-N-oxide/electron spin resonance (DMPO/ESR)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH ) (photometry) revealed that 3,3 0 ,4 0 ,5-tetrahydroxystilbene (IC 50 : 2.69 mM; k 9 : 443000 M À1 s À1 ), 3,4,4 0 ,5-tetrahydroxystilbene (IC 50 : 41.5 mM; k 9 : 882000 M À1 s À1 ) and 3,3 0 ,4,4 0 ,5,5 0 -hexahydroxystilbene (IC 50 : 5.02 mM), exerted a more than 6600-fold higher antiradical activity than resveratrol and its two other analogues. Furthermore, in HL-60 leukemic cells hydroxystilbenes with ortho-hydroxyl groups exhibited a more than three-fold higher cytostatic activity compared to hydroxystilbenes with other substitution patterns. Oxidation of ortho-hydroxystilbenes in a microsomal model system resulted in the existence of ortho-semiquinones, which were observed by ESR spectroscopy. Further experiments revealed that these intermediates undergo redox-cycling thereby consuming additional oxygen and forming cytotoxic oxygen radicals. In contrast to compounds with other substitution patterns hydroxystilbenes with one or two resorcinol groups (compounds 1 and 3) did not show an additional oxygen consumption or semiquinone formation. These findings suggest that the increased cytotoxicity of ortho-hydroxystilbenes is related to the presence of ortho-semiquinones formed during metabolism or autoxidation. #

Administration of silymarin (800 mg/kg i.p.) 30 min before carbon tetrachloride (18 pL/kg i.p.) did not modify total hepatic levels of CCI, and metabolites in mice, but decreased by 40% the in uivo covalent binding of Ccl, metabolites to hepatic lipids at 2 hr. This pretreatment decreased by 60% the exhalation of ethane during the first hour after Ccl,, and decreased by 50% the incidence of liver cell necrosis. In vitro, silymarin (800 pgg/mL) decreased by SO to 70% various monooxygenase activities, and decreased by 20% the covalent binding of CCl, metabolites lo microsomal proteins. Silymarin (800 pg/mL) decreased by 70% in vitro lipid peroxidation mediated by Ccl, metabolites, and decreased by 90% peroxidation mediated by NADPH alone. Silibinin, one of the three isomers composing silymarin, also decreased carbon tetrachloride-induced lipid peroxidation; this effect, however, was less than that of silymarin in oitro, and was more transient in oivo. Pretreatment with silibinin (800 mg/kg i.p.) 30 min before Ccl4 (18 pL/kg i.p.) did not improve SGPT activity or liver histology at 24 hr. We conclude that silymarin prevents carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice, firstly, by decreasing the metabolic activation of CCII, and, secondly, by acting as a chain-breaking

Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

Endocrine disruptors are man-made chemicals that can disrupt the synthesis, circulating levels, and peripheral action of hormones. The disruption of sex hormones was subject of intensive research, but thyroid hormone synthesis and signaling are now also recognized as important targets of endocrine disruptors. The neurological development of mammals is largely dependent on normal thyroid hormone homeostasis, and it is likely to be particularly sensitive to disruption of the thyroid axis. Here, we survey the main thyroid-disrupting chemicals, such as polychlorinated biphenyls, perchlorates, and brominated flame retardants, that are characteristic disruptors of thyroid hormone homeostasis, and look at their suspected relationships to impaired development of the human central nervous system. The review then focuses on disrupting mechanisms known to be directly or indirectly related to the transcriptional activity of the thyroid hormone receptors.

While Parkinson's disease (PD) traditionally has been defined by its characteristic motor hallmarks, non-motor features such as cognitive impairment and dementia are increasingly recognized as part of PD. Mild cognitive impairment is common in non-demented PD patients, occurring in about 20-50%. Frequency estimates and clinical features of mild cognitive impairment in PD (PD-MCI), however, vary across studies due to methodological differences and lack of uniform diagnostic criteria for PD-MCI. Overall, PD-MCI patients exhibit nonamnestic deficits in cognitive domains such as executive function, attention, and visuospatial function; however, the cognitive phenotype of PD-MCI is heterogeneous with some patients demonstrating greater amnestic deficits. PD-MCI patients, particularly those with posterior cortical profiles, may be at high risk for developing dementia. Various biomarkers studied in PD-MCI including cerebrospinal fluid, genetic analyses, and neuroimaging suggest that there may be distinct PD-MCI profiles. Future studies using uniform PD-MCI diagnostic criteria and incorporating biomarkers and longitudinal follow-up of PD-MCI cohorts are needed to understand PD-MCI as a transitional state between normal cognition and dementia.

Resveratrol is a natural molecule with antioxidant action. Moreover, resveratrol is also considered to be a molecule with anti-inflammatory action, an effect attributed to suppression of prostaglandin (PG) biosynthesis. The aim of the present study was to investigate the effects of resveratrol, a polyphenol present in most red wines, on reactive oxygen species formation as well as on arachidonic acid (AA) release, cyclooxygenase expression, and PG synthesis in murine resident peritoneal macrophages. Results show that resveratrol exerted a strong inhibitory effect on superoxide radical (O 2 Ϫ ) and hydrogen peroxide (H 2 O 2 ) produced by macrophages stimulated by lipopolysaccharides (LPS) or phorbol esters (PMA). Resveratrol also significantly decreased [ 3 H]AA release induced by LPS and PMA or by exposure to O 2

Screen, marked differences were observed. Evaluation of the activity profile using the COMPARE program revealed a different pattern for both agents: the cisplatin activity profile was similar to those of other diamine-platinum compounds, alkylating agents including melphalan, and camptothecin analogs, whereas the activity profile of oxaliplatin resembled those of other "dach" {diaminocyclohexane) platinum compounds and of acridine derivatives. The sensitivity profiles are influenced by the target(s)/mechanism(s) of action and the mechanism(s) of resistance of a drug. The dissimilarity in profiles suggests that these two platinum compounds have a different target(s)/mechanism(s) of action, a different mechanism(s) of resistance, or most likely both. Studies evaluating combinations of cisplatin/oxaliplatin suggest that the activities of these two agents are at least additive and possibly synergistic. Oxaliplatin has a different spectrum of activity and low cross-resistance to cisplatin and should be valuable in cisplatin refractory patients or in combination with cisplatin.

C-Phycocyanin (C-PC), the major light harvesting biliprotein from Spirulina platensis is of greater importance because of its various biological and pharmacological properties. It is a water soluble, non-toxic fluorescent protein pigment with potent anti-oxidant, anti-inflammatory and anti-cancer properties. In the present study the effect of highly purified C-PC was tested on growth and multiplication of human chronic myeloid leukemia cell line (K562). The results indicate significant decrease (49%) in the proliferation of K562 cells treated with 50 μM C-PC up to 48 h. Further studies involving fluorescence and electron microscope revealed characteristic apoptotic features like cell shrinkage, membrane blebbing and nuclear condensation. Agarose electrophoresis of genomic DNA of cells treated with C-PC showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 25 and 50 μM C-PC for 48 h showed 14.11 and 20.93% cells in sub-G0/G1 phase, respectively. C-PC treatment of K562 cells also resulted in release of cytochrome c into the cytosol and poly(ADP) ribose polymerase (PARP) cleavage. These studies also showed down regulation of anti-apoptotic Bcl-2 but without any changes in pro-apoptotic Bax and thereby tilting the Bcl-2/Bax ratio towards apoptosis. These effects of C-PC appear to be mediated through entry of C-PC into the cytosol by an unknown mechanism. The present study thus demonstrates that C-PC induces apoptosis in K562 cells by cytochrome c release from mitochondria into the cytosol, PARP cleavage and down regulation of Bcl-2.

Treatment of tuberculosis has become a challenge due to the rapid increase of multidrug and extensive
drug resistant Mycobacterium tuberculosis. Medicinal plants might represent a possible source for new potent
antibacterials to which pathogen strains are not resistant. In this study, five Combretum plant species-Combretum
imberbe, Combretum zeyheri, Combretum hereroense, Combretum elaeagnoides and Combretum platypetalum
used in traditional medicine were exposed to susceptibility tests to determine the effects of drug accumulation in
avirulent M. smegmatis and M. aurum. The MIC values of the potent plant species was then determined. Using
the agar disc diffusion assay, it was found out that the only the ethanolic extract from Combretum imberbe was
active on M. smegmatis and it had an MIC of 125 μg/ml in the broth microdilution assay. However, using Sabouraud
dextrose broth, Combretum platypetalum was found to have antimycobacterial effects which were not detected when
using the agar disc diffusion assay. MIC of 63 and 125 μg/ml and MBCs of 250 and 500 μg/ml were obtained for C.
platypetalum for M. smegmatis and M. aurum respectively. C. imberbe extract gave an MIC of 125 μg/ml but did not
produce MBCs suggesting that it is bacteriostatic and not bactericidal. Drug accumulation transport assays were
performed on C. imberbe, C. hereroense and C. platypetalum and results show that extracts from two plants are
efflux pump inhibitors. Determination of the IC50 for the transport process was as conducted on Combretum imberbe
using CCCP as the standard inhibitor. Both plants extract in addition to C. hereroense maybe potential sources for
leads for efflux pump inhibitor in mycobacteria.

Extensive research within the last two decades has revealed that most chronic illnesses, including cancer, diabetes, and cardiovascular and pulmonary diseases, are mediated through chronic inflammation. Thus, suppressing chronic inflammation has the potential to delay, prevent, and even treat various chronic diseases, including cancer. Various nutraceuticals from fruits, vegetables, vitamins, spices, legumes, and traditional Chinese and Ayurvedic medicine have been shown to safely suppress proinflammatory pathways; however, their low bioavailability in vivo limits their use in preventing and treating cancer. We describe here the potential of nanotechnology to fill this gap. Several nutraceuticals, including curcumin, green tea polyphenols, coenzyme Q, quercetin, thymoquinone and others, have been packaged as nanoparticles and proven to be useful in “nanochemoprevention” and “nano-chemotherapy”.

The presence of a residual amount of unstable proteins in wines is a concern for winemakers because these polymers can precipitate from solution during storage causing appearance of sediments and hazes. Such precipitates are commonly the result of denaturation and subsequent aggregation of heat-unstable wine proteins. It has been demonstrated that the vast majority of the wine proteins derive from grapes and that proteins responsible for haze formation are Pathogenesis-Related (PR) proteins, in particular thaumatin-like (TL) proteins and chitinases. Moreover, these proteins are highly resistant to acidic pHs, proteolysis and fermentation conditions. However, they can became insoluble during wine storage and thus originate perceptible turbidity in the bottles. Despite the efforts made in the recent past, the white wine protein instability is still a main problem during white wine making and bentonite treatments are even now indispensable to stabilise white wines.