Physiological Interactions of Nanoparticles in Energy Metabolism, Immune Function and Their Biosafety: A Review.

Nanoparticles owing to their unique physico-chemical properties have found its application in various biological processes, including metabolic pathways taking place within the body. This review tried to focus the involvement of nanoparticles in metabolic pathways and its influence in the energy metabolism, a fundamental criteria for the survival and physiological activity of living beings. The human body utilizes energy derived from food resources through a series of biochemical reactions involving several enzymes, co-factors (metals, non-metals, vitamins etc.) through the metabolic pathways (glycolysis, tri carboxylic acid cycle, oxidative phosphorylation, electron transport chain, etc.) in cellular system. Energy metabolism is also involved in the immune networking of the body for self defence and against pathophysiology. The immune system comprises of different cells and tissues, bioactive molecules for self defence and to fight against diseases. In the recent times, it has been reported through in vivo and in vitro studies that nanoparticles have direct influence on body's immune functions, and can modulate immunity by either suppressing or enhancing it. A comprehensive overview of nanoparticles and its involvement in immune function of the body in normal and pathophysiological conditions has been discussed. Considering these perspectives on nanoparticle interaction another important area which has been highlighted is the biosafety issues which are necessary before therapeutic applications. It is expected that development of physiologically compatible nanoparticles controlling energy metabolic processes, immune functions may show new dimension in the pathophysiology linked with energy and immunity.

Physiologically important metal nanoparticles and their toxicity.

Nanotechnology has been setting benchmarks for the last two decades, but the origins of this technology reach back to ancient history. Today, nanoparticles of both metallic and non-metallic origin are under research and development for applications in various fields of biology/therapeutics. Physiologically important metals are of concern because they are compatible with the human system in terms of absorption, assimilation, excretion, and side effects. There are several physiologically inorganic metals that are present in the human body with a wide range of biological activities. Some of these metals are magnesium, chromium, manganese, iron, cobalt, copper, zinc, selenium and molybdenum. These metals are synthesized in the form of nanoparticles by different physical and chemical methods. Physiologically important nanoparticles are currently under investigation for their bio-medical applications as well as for therapeutics. Along with the applicative aspects of nanoparticles, another domain that is of great concern is the risk assessment of these nanoparticles to avoid unnecessary hazards. It has been seen that these nanoparticles have been shown to possess toxicity in biological systems. Conventional physical and chemical methods of metal nanoparticle synthesis may be one possible reason for nanoparticle toxicity that can be overcome by synthesis of nanoparticles from biological sources. This review is an attempt to establish metal nanoparticles of physiological importance to be the best candidates for future nanotechnological tools and medicines, owing to the acceptability and safety in the human body. This can only be successful if these particles are synthesized with a better biocompatibility and low or no toxicity.

In vivo and in vitro antileishmanial activity of Bungarus caeruleus snake venom through alteration of immunomodulatory activity.

Leishmaniasis threatens more than 350 million people worldwide specially in tropical and subtropical region. Antileishmanial drugs that are currently available have various limitations. The search of new drugs from natural products (plants, animals) possessing antileishmanial activity is ventured throughout the world. The present study deals with the antileishmanial activity of Bungarus caeruleus snake venom (BCV) on in vitro promastigotes and amastigotes of Leishmania donovani parasite and leishmania infected BALB/c mice. The effect of BCV on peritoneal macrophage, release of cytokines from the activated macrophages, production of nitric oxide, reactive oxygen species and cytokines were studied in vivo and in vitro. IC50 value of BCV on L. donovani promastigote was 14.5 µg/ml and intracellular amastigote was 11.2 µg/ml. It activated peritoneal macrophages, significantly increased cytokines and interleukin production. BCV (20 µg/kg and 40 µg/kg body weight of mice) decreased parasite count by 54.9% and 74.2% in spleen and 41.4% and 60.4% in liver of infected BALB/c mice. BCV treatment significantly increased production of TNF-α, IFN-γ, ROS, NO in infected mice. Histological studies showed decreased granuloma formation in treated liver as compared with control. Liver and spleen structure was partially restored due to BCV treatment in infected mice. The present study revealed that BCV possessed antileishmanial activity against L. donovani parasite in vivo and in vitro and this activity was partly mediated through immunomodulatory activity involving macrophages.

Inhibition of toxic actions of phospholipase A2 isolated & characterized from the Indian Banded Krait (Bungarus fasciatus) venom by synthetic herbal compounds.

BACKGROUND & OBJECTIVES: Phospholipase A2 (PLA2 ) is one of the major constituents of krait venom associated with several pathophysiological actions like myotoxicity, cardiotoxicity, neurotoxicity, etc. As there was no specific antiserum available against Bungarus fasciatus venom, this study was done with synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum to neutralize the PLA2 induced toxicities in experimental models. METHODS: B. fasciatus venom phospholipase A2 fraction 38 (BF-38) was isolated by ion exchange chromatography, molecular weight was determined by mass spectrometry and its N terminal amino acid sequence was identified. Monospecific rabbit antiserum was raised against the PLA2 in presence of Freund complete adjuvant. The neutralization of PLA2 induced toxicities was done in in vitro and in in vivo models using synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum. RESULTS: A toxic PLA2 (BF-38) was purified from the B. fasciatus venom by CM-cellulose and HPLC, of 13.17 kDa and a minor band of 7.3 kDa using ESI-MS. The 13.17 kDa PLA2 sequence was NLYQFKNMIQC. The 7.3 kDa toxin sequence was RKCLTKYSQDNES and was found to be <10 per cent w/w. Anti PLA2 rabbit antiserum produced faint precipitant band in immunogel diffusion and showed low titre value. The commercial polyvalent snake venom antiserum, anti PLA2 rabbit antiserum and the synthetic herbal compounds neutralized the PLA2 induced toxicities at different intensities. INTERPRETATION & CONCLUSIONS: Our results suggested that synthetic herbal compound (BA) along with antiserum might provide effective protection against PLA2 induced toxicities of B. fasciatus venom.

Ethno biological usage of zoo products in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune disorder which causes swelling, redness, pain, stiffness, restriction of limb movements, decreases life expectancy and early death of the patients. Available drugs include non steroidal anti-inflammatory and analgesics, disease modifying anti-rheumatic drugs and steroids (glucocorticoids etc). All these drugs have their own limitations such as gastrointestinal irritations, cardiovascular problems, and drug dependency. Search for alternative therapy from natural products are being ventured throughout the world. Zoo therapy in arthritis, a common practice of the ancient times that have been mentioned in traditional and folk medicine. The scientific basis of some of the zoo products are being explored and have been showing promising results in experimental rheumatoid arthritis. These therapies have minimum side effects and many of them have potential to give rise to drug development clues against rheumatoid arthritis. The present review is an effort to establish the folk and traditional treatment of rheumatoid arthritis using zoo products.

Experiences and Perspectives of Patients with Non-HIV-Associated Lipodystrophies and Their Caregivers: A Qualitative Study.

BACKGROUND: Lipodystrophy comprises a group of conditions characterized by loss of functional adipose tissue, resulting in severe metabolic complications and a complex range of symptoms. OBJECTIVE: This study sought to gain a holistic understanding of the impact of congenital or non-human immunodeficiency virus acquired lipodystrophies on the quality of life of patients and their caregivers and to capture the impact of lipodystrophy on quality of life using a standard instrument. METHODS: Ten patients with lipodystrophies and five caregivers from the USA and UK were recruited through convenience sampling and interviewed using a semi-structured questionnaire containing open-ended questions about disease symptoms and attributes and numerical rating scales to prompt discussion of symptom prevalence and impact. After the interview, participants filled out the 36-Item Short Form (SF-36) survey instrument. Conventional conceptual content analysis methods were used to analyze the anonymized transcripts. RESULTS: Four concepts were developed: diagnostic journey and symptom management, burden of disease, healthcare resource utilization, and support and advocacy. Participants described lengthy diagnostic journeys and frequent interactions with healthcare systems. Many participants became experts on lipodystrophy through the diagnostic journey and described difficulties accessing effective treatment, even after diagnosis. Both patients and caregivers emphasized the ongoing burden of living with lipodystrophy and the accompanying sense of isolation. Participants turned to disease-specific support groups to cope, engaging in knowledge sharing with other patients and caregivers and developing friendships based on shared experiences. Ten participants completed the SF-36, with a mean (standard deviation) SF-36 score of 0.6 (0.2). CONCLUSIONS: Currently, there are no qualitative studies that describe the experiences of patients with lipodystrophy and their caregivers. While additional research is needed, educational work like this study is a promising first step that could lead to early diagnosis and access to treatment and support.

Effects of Metreleptin on Patient Outcomes and Quality of Life in Generalized and Partial Lipodystrophy.

Generalized and partial lipodystrophy are rare and complex diseases with progressive clinical and humanistic burdens stemming from selective absence of subcutaneous adipose tissue, which causes reduced energy storage capacity and a deficiency of adipokines such as leptin. Treatment options were limited before leptin replacement therapy (metreleptin) became available. This retrospective study evaluates both clinical and humanistic consequences of the disease and treatment. Chart data were abstracted from a cohort of metreleptin-treated patients with generalized and partial lipodystrophy (n = 112) treated at the US National Institutes of Health. To quantify the quality-of-life consequences of the lipodystrophy disease attributes recorded in chart data, a discrete choice experiment was completed in 6 countries (US, n = 250; EU, n = 750). Resulting utility decrements were used to estimate the quality-adjusted life-year consequences of changes in lipodystrophy attribute prevalence before and after metreleptin. In addition to metabolic impairment, patients with generalized and partial lipodystrophy experienced a range of lipodystrophy consequences, including liver abnormality (94%), hyperphagia (79%), impaired physical appearance (77%), kidney abnormality (63%), reproductive dysfunction (80% of females of reproductive age), and pancreatitis (39%). Improvement was observed in these attributes following initiation of metreleptin. Quality-adjusted life-year gains associated with 12 months of treatment with metreleptin were estimated at 0.313 for generalized and 0.117 for partial lipodystrophy, reducing the gap in quality of life between untreated lipodystrophy and perfect health by approximately 59% and 31%, respectively. This study demonstrates that metreleptin is associated with meaningful clinical and quality-of-life improvements.

Herbs and herbal constituents active against snake bite.

Snake bite, a major socio-medical problem of south east asian countries is still depending on the usage of antisera as the one and only source of treatment, which has its own limitations. In India, mostly in rural areas, health centres are inadequate and the snake bite victims mostly depend on traditional healers and herbal antidotes, as an alternative treatment. The present review has been focussed on the varied folk and traditional herbs and their antisnake venom compounds, which might be a stepping stone in establishing the future therapy against snake bite treatment and management.

Financial Implications of Avapritinib for Treatment of Unresectable Gastrointestinal Stromal Tumors in Patients With a PDGFRA Exon 18 Variant or After 3 Previous Therapies in a Hypothetical US Health Plan.

Importance: With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 variant, including PDGFRA D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget. Objective: To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a PDGFRA exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan. Design, Setting, and Participants: For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased PDGFRA testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic PDGFRA exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%. Exposures: The model compared scenarios with and without avapritinib in a formulary. Main Outcomes and Measures: Annual, total, and per member per month (PMPM) budget impact. Results: In a hypothetical 1-million member plan, fewer than 0.1 new patients with a PDGFRA exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a PDGFRA exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3. Conclusions and Relevance: These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.

Gold Nanoparticles (AuNPs) Conjugated with Andrographolide Ameliorated Viper (Daboia russellii russellii) Venom-Induced Toxicities in Animal Model.

Andrographolide, a diterpenoid compound found in the aerial parts of Andrographis paniculata (a well known anti snake venom plant) was conjugated with gold nanoparticle (andrographolide-AuNPs) and its efficacy against Daboia russellii russellii venom (DRRV) induced local damage, organ toxicity and inflammatory response was evaluated in animal models. Ethical clearance was obtained before animal experiments. Andrographolide-AuNPs was formed by adsorption method. Physico-chemical characterization of particle was done by dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Swiss albino male mice were divided into 5 groups: Gr. 1-Sham control, Gr. 2-DRRV control, Gr. 3-anti snake venom serum treated, Gr. 4-andrographolide treated and Gr. 4-andrographolide-AuNPs treated. 1/5th minimum lethal dose of DRRV (10 µg/s.c./20 g mice) was induced in animals of group 2, 3, 4 and 5 animals, followed by treatment with anti snake venom serum (2 mg/20 g mice, i.v.) andrographolide (50 µg/20g mice, i.p.) and andrographolide-AuNPs (50 µg/20 g mice, i.v.) in group 3, 4 and 5 animals, respectively. Blood was collected after 18 h, serum was prepared and organ toxicity markers (transaminases, phosphatases, lactate dehydrogenase, creatine phosphate, urea, creatinine, Ca2+, phosphorous), inflammatory markers (interleukin 1ß, 6, 17a, 10, tumor necrosis factor α) and local damage testings (defibrination, edema, hemorrhage) were assessed. Values were expressed as mean ± SEM (n = 4), one way analysis of variance was done, P < 0.05 was considered as statistically significant. Formed andrographolide-AuNPs were pink in color with hydrodynamic diameter 30-50 nm, polydispersity index 0.412 and zeta potential -16.21 mV. XRD data confirmed the presence of crystalline gold in andrographolide-AuNPs. TEM (20-50 nm) and FE-SEM (20-25 nm) indicated the presence of nearly spherical particle. DRRV envenomation followed by treatment with andrographolide-AuNPs provided protection against venom induced edema, hemorrhage, defibrination, organ toxicity and inflammation in animal model. Venom neutralization by andrographolide-AuNPs was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation, may be due to anti-oxidant/anti-inflammatory activity of andrographolide, showing increased efficacy after gold nanoparticle tagging. Thus, andrographolide-AuNPs may serve as a supportive therapy in snakebite (against venom induced local damage, organ toxicity and inflammatory response) subject to further detail studies.

Cost-Effectiveness of a Small Intrapericardial Centrifugal Left Ventricular Assist Device.

There is limited data on the cost-effectiveness of continuous-flow left ventricular assist devices (LVAD) in the United States particularly for the bridge-to-transplant indication. Our objective is to study the cost-effectiveness of a small intrapericardial centrifugal LVAD compared with medical management (MM) and subsequent heart transplantation using the respective clinical trial data. We developed a Markov economic framework. Clinical inputs for the LVAD arm were based on prospective trials employing the HeartWare centrifugal-flow ventricular assist device system. To better assess survival in the MM arm, and in the absence of contemporary trials randomizing patients to LVAD and MM, estimates from the Seattle Heart Failure Model were used. Costs inputs were calculated based on Medicare claim analyses and when appropriate prior published literature. Time horizon was lifetime. Costs and benefits were appropriately discounted at 3% per year. The deterministic cost-effectiveness analyses resulted in $69,768 per Quality Adjusted Life Year and $56,538 per Life Year for the bridge-to-transplant indication and $102,587 per Quality Adjusted Life Year and $87,327 per Life Year for destination therapy. These outcomes signify a substantial improvement compared with prior studies and re-open the discussion around the cost-effectiveness of LVADs.

Experimental osteoporosis induced in female albino rats and its antagonism by Indian black scorpion (Heterometrus bengalensis C.L.Koch) venom.

The present study was designed to explore the antiosteoporosis activity of the Indian black scorpion (Heterometrus bengalensis) venom on experimental osteoporosis female albino rats. Sham operated control rats were designated as Gr I, Gr II animals served as osteoporosis control, Gr III osteoporosis rats were treated with SV (1/25th of MLD), Gr IV osteoporosis rats were treated with 1/50th of MLD of SV and Gr V osteoporosis rats were treated with standard (calcium and vit-D3). As compared with the Gr I rats, the Gr II rats showed typical osteoporosis changes in increased of urinary Ca(2+), PO(4)(3-), CRE, OH-P levels, serum/plasma Ca(2+), PO(4)(3-), TRAP, IL1, IL6, TNFalpha and PTH level, bone Ca(2+), PO(4)(3-), Mg(2+), Zn(2+) and decreased level of serum/plasma ALP, EST and PTH, bone Na(+). In Gr III, Gr IV and Gr V rats, the osteoporosis changes of urine, serum and bone, were significantly restored as compared with the Gr II rats. The bone dimensions, morphology and histological changes observed in Gr II rats were restored in Gr III, Gr IV and Gr V rats. This study confirms that the Indian black scorpion venom may influence bone remodeling process by stimulating bone formation and reducing bone resorption process of osteogenesis.

Indian black scorpion (Heterometrus bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562.

Venoms are rich source of several bioactive compounds that possess therapeutic potentials. The different constituents of scorpion venom can modulate cell proliferation, cell growth and cell cycle. In the present communication, the cytotoxic activity of Indian black scorpion (Heterometrus bengalensis) venom was explored on human leukemic U937 and K562 cells. Scorpion venom induced U937 and K562 cell growth inhibition and the IC(50) value calculated to be 41.5 microg/ml (U937) and 88.3 microg/ml (K562). The scorpion venom showed characteristic features of apoptosis such as membrane blebbing, chromatin condensation and DNA degradation in both the cells as evidenced by confocal, fluorescence, scanning electron microscopy. Scorpion venom (IC(50) dose, 48 h) induced DNA fragmentation as evidenced by comet formation. Flow-cytometric assay revealed a significant amount of apoptotic cells (early and late) due to scorpion venom treatment. The venom induced cell cycle arrest was observed with maximum cell accumulation at sub-G(1) phase. Thus, the Indian scorpion (H. bengalensis) venom possessed antiproliferative, cytotoxic and apoptogenic activity against human leukemic cells.

A crystalline compound (BM-ANF1) from the Indian toad (Bufo melanostictus, Schneider) skin extract, induced antiproliferation and apoptosis in leukemic and hepatoma cell line involving cell cycle proteins.

In our earlier communication, it was reported that Indian toad (Bufo melanostictus) skin extract (TSE) possesses antiproliferative and apoptogenic activity in U937 and K562 cells [Giri et al., 2006. Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract in U937 and K562 cells. Toxicon 48 (4), 388-400]. In the present study, a compound (BM-ANF1) has been isolated from the TSE by alumina gel column chromatography, crystallized and evaluated for its antiproliferative and apoptogenic activity in U937, K562 and HepG2 cells. BM-ANF1 produced dose-dependent inhibition of U937, K562 and HepG2 cell growth. The antiproliferative activity was reflected by the MTT assay and demonstrated by the reduced expression of proliferative cell nuclear antigen (PCNA). Flow-cytometric analysis showed that BM-ANF1 arrested the cell cycle at G1 phase and enhanced annexin-V binding in U937 and K562 cells. Scanning electron microscopic and fluorescent microscopic analysis of U937 and K562 cells revealed the apoptogenic nature of the compound. Alkaline comet assay showed that BM-ANF1 produced DNA fragmentation. The dose-dependent expression of caspase 3 indicated that the apoptogenic properties of BM-ANF1 were mediated through the activation of downstream effector nucleases in the cancer cells. The increased expression of p53 and moderate expression of p21(Cip1)/p27(Kip1) due to BM-ANF1 treatment in HepG2 cells supported that the apoptogenic activity of BM-ANF1 was mediated through p53 tumor-suppressor gene expression followed by the expression of p21(Cip1) and p27(Kip1) and it was likely to be linked with cell cycle arrest at G1 phase in cancer cells. From the present study, it may be suggested that the crystalline compound, BM-ANF1, was antiproliferative and apoptogenic in human leukemic and hepatoma cells.

A heat stable protein toxin (drCT-I) from the Indian Viper (Daboia russelli russelli) venom having antiproliferative, cytotoxic and apoptotic activities.

A heat stable 7.2kDa protein toxin (drCT-I) has been purified and crystallized from Indian Daboia russelli russelli venom (Roy Choudhury et al., 2006. Acta Cryst. F Struct Biol Cryst Commun, 62(Pt. 3), 292). The N-terminal (first 20) amino acid sequence of drCT-I was LKCNKLVPLFYKTCPAGKNL, which showed sequence homology to cytotoxins isolated from Naja venom. drCT-I has been evaluated for anticancer activity against EAC cells in vivo and human leukemic cells (U937, K562) in vitro. drCT-I (125 microg/kg, i.p/day for 10 days) significantly decreased EAC cell count, cell viability (p<0.001) and significantly increased the survival time of tumour bearing mice (T/C% 178.64, p<0.01) in comparison to untreated tumour bearing control. drCT-I, produced dose and time-dependent inhibition of U937 and K562 cell growth and had an IC50 of 8.9 and 6.7 microg/ml respectively after 24h treatment. The reduced MTT values after drCT-I treatment indicated its cytotoxic nature, which supported its antiproliferative action. Scanning electron microscopy and confocal microscopy in U937 and K562 cells after drCT-I treatment indicated certain features of apoptosis such as membrane blebbing, perforations, nuclear fragmentation. The induction of apoptosis was further confirmed by phosphatidylserine externalization observed using annexinV-FITC/PI staining and flow cytometric analysis. drCT-I brought about apoptosis by G1 phase arrest of the cell cycle. The effect of drCT-I on normal human peripheral blood mononuclear cell (PBMNC) viability and cytotoxicity was studied in culture and was found to be lower than that on U937 and K562 cells. Thus both in vivo and in vitro experimental results suggested that drCT-I possessed anticancer potential.

Venom of Indian monocellate cobra and Russell's viper show anticancer activity in experimental models.

Indian monocellate cobra (Naja kaouthia) and Russell's viper (Vipera russelli) are common snakes of the East Indian sub-peninsula. The anticarcinogenic activities of their crude venoms were studied on carcinoma, sarcoma and leukemia models. Sub-lethal doses of venoms showed cytotoxicity on Ehrlich ascites carcinoma (EAC) cells in vivo. The venoms increased lifespan of EAC mice and strengthened the impaired host antioxidant system. Sarcoma formation in mice (3-methylcholanthrene induced) after venom treatment was significantly less (p < 0.005). Histopathological examination of tumors showed tissue necrosis. The venoms displayed potent cytotoxic and apoptogenic effect on human leukemic cells (U937/K562). The venoms reduced cell proliferation rate (p < 0.005) and produced morphological alterations indicative of apoptosis induction. Different degree and nature of anticarcinogenic property of cobra and viper venoms may be attributed to the difference in their constituents.

Bioactive molecules from amphibian skin: their biological activities with reference to therapeutic potentials for possible drug development.

The amphibian skin contains various bioactive molecules (peptides, proteins, steroids, alkaloids, opiods) that possess potent therapeutic activities like antibacterial, antifungal, antiprotozoal, antidiabetic, antineoplastic, analgesic and sleep inducing properties. Research on amphibian skin derived biomolecules can provide potential clue towards newer drug development to combat various pathophysiological conditions. An overview on the bioactive molecules of various amphibian skins has been discussed.

Therapeutic potential of krait venom.

Kraits belong to Elapideae and are widely distributed in East and South-East Asian countries. Krait venom possesses neurotoxins, membrane toxins, cardiotoxins, three finger toxins, metalloproteinases, cholinesterases, L-amino acid oxidases and serine proteases. The therapeutic potential of krait venom in pathophysiological conditions such as microbial and parasitic infections, cancer, arthritis, inflammation and blood coagulation disorder is discussed in this review. More intensive new research ventures are required to establish the therapeutic potential of krait venom in complex and emerging diseases.

Purification, crystallization and preliminary X-ray structural studies of a 7.2 kDa cytotoxin isolated from the venom of Daboia russelli russelli of the Viperidae family.

A cytotoxin (MW 7.2 kDa) from Indian Russell's viper (Daboia russelli russelli) venom possessing antiproliferative activity, cardiotoxicity, neurotoxicity and myotoxicity has been purified, characterized and crystallized. The crystals belong to the tetragonal space group P4(1), with unit-cell parameters a = b = 47.94, c = 50.2 A. Larger crystals, which diffracted to 1.5 A, were found to be twinned; diffraction data were therefore collected to 2.93 A resolution using a smaller crystal. Molecular-replacement calculations identified two molecules of the protein in the asymmetric unit, which is in accordance with the calculated VM value.