An increase in drug safety concerns in recent years with some high profile drug withdrawals have led to raising the bar by various stakeholders more importantly by the regulatory authorities. The number of Adverse Drug Reactions (ADRs) reported have also resulted in an increase in the volume of data handled and to understand pharmacovigilance a high level of expertise is required to rapidly detect drug risks as well as to defend the product against an inappropriate removal. Proactive pharmacovigilance throughout the product life cycle is the way forward and the future direction for drug safety. It is a challenge to codify and standardize the act of signal detection and risk management in the context of clinical trials and post-marketing pharmacovigilance. While major advancements of the discipline of oharmacovigilance have taken place in the West, not much has been achieved in India. However, with more clinical trials and clinical research activity being conducted in India, there is an immense need to understand and implement pharmacovigilance. For this to happen in India, the mind set of people working in regulatory agency (DCGI Office) and the Indian Pharmaceutical companies need to change. This article describes and discusses the various strategies and proposals to build, maintain and implement a robust pharmacovigilance system for various stakeholders and eventually make it happen in India!

Objective : To conduct a systematic review of literature on interactions between conventional drugs and various herbs. Materials and Methods : We carried out a literature survey to assess published herb-drug interaction information in clinical case reports and case series to check the report reliabilities. Results : From 133 cases of suspected interactions, 67% cases were classified as possible interactions, 27% cases were unable to be evaluated and only 6% of the cases were well-documented. St. John's wort was the most common herb involved (37 cases) in drug interactions. Warfarin was the most common drug (34 cases) interacting with various herbs. Conclusion : Herb-drug interactions are a stark reality today. Hence, proper reporting of cases, careful vigilance, evidence-based appraisal and constantly updated reviews of such herb-drug interactions are very important to promote systematic research.

Objectives : Lantadene A (LA, 22β -angeloyloxy-3-oxoolean-12-en-28-oic acid) a pentacyclic, triterpenoid isolated from the leaves of the obnoxious weed, Lantana camara L. was evaluated for apoptosis induction in the human leukemia HL-60 cell line. Materials and Methods : The effect of LA on cell proliferation of HL-60 cancer cells was determined by using the MTT assay. The morphological effects of LA-treated HL-60 cancer cells were observed under a fluorescence microscope. DNA fragmentation was observed using gel electrophoresis. Flow cytometry was carried out to observe changes in the cell cycle distribution of the cells. The expression of Bcl-2 and Bax proteins in HL-60 cells was visualized by means of an immunohistochemical assay and cell viability was determined upon treatment with DEVD-CHO (inhibitor of caspase-3) and LA. Results : Typical morphological changes including cell shrinkage, chromatin condensation and characteristic DNA ladder formation in agarose gel electrophoresis were observed. LA-induced marked concentration- and time-dependent inhibition of cancer cell proliferation with an IC ₅₀ value of 19.8 ± 0.10 µg/ml following 48 h incubation. Flow cytometric analysis showed suppressed cell proliferation associated with cell cycle arrest in the G ₀ /G ₁ phase. LA significantly inhibited cell proliferation of HL-60 cells and induced cell apoptosis by downregulating Bcl-2 and upregulating Bax expression. The peptidic caspase-3 inhibitor, DEVD-CHO (NH ₂ -Asp-Glu-Val-Asp-CHO, 2 µM), increased the viability of HL-60 cells, which had been previously treated with LA. Conclusions : The results indicated that LA induces efficient cell apoptosis by activating the caspase-3 pathway and through down- and upregulation of Bcl-2 and Bax expression respectively.

Objective : Toxicity of pesticides is thought to be due to reactive oxygen species (ROS). Due to their antioxidant property, polyphenols in plant extracts may afford protection from pesticide toxicity. In the present study, we evaluated the protective effect of a butanolic extract of Paronychia argentea L. against toxicity caused by the organophosphorus pesticide, chloropyriphos ethyl (CE). Materials and Methods : Pregnant albino Wistar rats were used. Pesticide and plant extract were administered daily by oral gavage from the 6 ^th to the 15 ^th day of gestation. Plasma and tissue malondialdehyde (MDA), blood reduced glutathione (GSH) and erythrocyte superoxide dismutase (SOD) activities were estimated. MDA levels were estimated in plasma and different organs (liver, kidney, brain, placenta and in the fetuses and their livers) as an indicator of lipid peroxydation (LPO). Results : The data showed a significant increase in plasma and tissue LPO levels in animals treated with the pesticide while the effect was attenuated by the plant extract (CE-ex). Also, CE caused a significant decrease in antioxidant enzyme activity and this effect was partially reversed in groups treated with the plant extract. The pesticide induced embryotoxicity and resulted in resorption, fetal death and a reduced implant number. Conclusion : It can be concluded that CE can lead to an increase in LPO production in adult and fetal tissues, while treatment with the plant extract leads to protection against CE toxicity. The decrease in LPO levels and the increase in GSH and SOD enzyme activities after treatment with the plant extract revealed its antioxidant property.

Objective : To evaluate the possible role of the antioxidant activity of the polyherbal formulation, NR-ANX-C and its individual components in reversing haloperidol-induced catalepsy in Swiss albino mice. Materials and Methods : Catalepsy was induced with haloperidol (1 mg/kg i.p) in 13 groups of male albino mice (n = 6 / group). Three groups received NR-ANX-C (10, 25, 50 mg/kg), three groups received Withania somnifera (1.7, 4.25, 8.5 mg/kg), another three groups Ocimum sanctum (1.7, 4.25, 8.5 mg/kg), three other groups Camellia sinensis (3.4, 8.5, 17 mg/kg) and one group received the vehicle (1% Gum acacia) orally, 30 minutes prior to haloperidol administration, for a duration of seven days. Animals were sacrificed on the seventh day and superoxide dismutase (SOD) activity was estimated in the brain. Results : A significant (P < 0.01) reduction in the cataleptic scores was observed in all the drug-treated groups as compared to the control, with maximum reduction in the NR-ANX-C 25 mg/kg group. Similarly, a reduction in SOD activity was observed in the NR-ANX-C-, O. sanctum- and the W. somnifera-treated groups. An increase in SOD activity was observed in the C. sinensis-treated groups. Conclusion : With the exception of C. sinensis, the antioxidant potential of NR-ANX-C and its individual constituents has contributed to the reduction in the oxidative stress and the catalepsy induced by haloperidol administration.

Objective : In vitro hemolytic activity of the tentacle extract of Paracondylactis indicus (Dave), a sea anemone found in the eastern coastal region of West Bengal (India), was determined in rat erythrocytes. Materials and Methods : Acute toxicity study was carried out with the tentacle extract followed by detailed biochemical studies to evaluate the direct and indirect hemolytic activities of the extract. The effects of pH, temperature, divalent cations and chelating agents on hemolysis were also evaluated. Efforts were also made to elucidate the mechanism of the hemolytic activity of the extract. Results : The tentacle extract of P. indicus (Dave) produced significant hemolysis (both direct and indirect) in washed rat erythrocytes. The direct hemolytic activity of the tentacle extract was found to be both temperature- and pH-dependent. Divalent cations (Ca ²⁺ , Mg ²⁺ ) produced significant enhancement of direct hemolytic activity. Hemolysis (both direct and indirect) was significantly diminished in the presence of Zn ²⁺ , EDTA and p-bromophenacyl bromide. The tentacle extract was found to induce lipid peroxidation in washed erythrocytes, which was inhibited by chlorpromazine. The tentacle extract demonstrated significant proteolytic activity, which was found to decrease in the presence of protease inhibitors (EDTA, EGTA and PMSF). Conclusion : P. indica tentacle extract (and in particular, the 60% cut fraction) probably contains enzymatic components like phospholipase(s) along with proteases, which may be the contributing factors for its observed hemolytic activity.

Objective : To develop a rapid liquid chromatography / mass spectrometry / mass spectrometry (LC/MS/MS) method for testing of glucocorticosteroids, which are banned in sports by the World Anti-doping Agency from January 1 ^st 2004. Materials and Methods : A total of 14 glucocorticosteroids were analyzed on LC/MS/MS using an Inertsil^® ODS-3 (3.0 µm, 50 mm ´ 4.6 mm i.d.) C-18 column in atmospheric pressure chemical ionization mode (positive ionization) with a mobile phase consisting of ammonium acetate and acetonitrile. The analytical equipment used was Aglient 1100 HPLC and API-3200 Triple quadrupole mass spectrometer. Results : All glucocorticosteroids could be detected within 8 minutes. The limit of detection of all glucocorticosteroids by this screening method was 1 ng/ml. The recovery percentage at 25 and 50 ng/ml concentrations ranged from 54% (Prednisone) to 144% (Methylprednisolone).The validated method has been used successfully for testing of 500 in-competition samples. Excretion study samples of budesonide, methyl prednisolone and prednisone were analyzed by this method and the parent drugs as well as metabolites could be detected. However, further work is in progress to combine this procedure with another LC/MS/MS procedure in the ESI mode (positive ionization) being used for few anabolic steroids and heat-labile stimulants. This would help in screening of all corticosteroids, few anabolic agents and stimulants with just one injection, thus saving time and effort.