Poly-l-Lysine inhibits VEGF and c-Myc mediated tumor-angiogenesis and induces apoptosis in 2D and 3D tumor microenvironment of both MDA-MB-231 and B16F10 induced mice model.

Cancer is a widespread disease that has shown promising mortality worldwide. Our previous study has been shown the efficacy of Poly-l-lysine (PLL) as a promising cytotoxic effect against cancer cells. However, exact-mechanism of PLL in 3D physiological relevant tumor-microenvironment and against tumor-angiogenesis has never been analysed. In this study, we have investigated apoptotic efficacy of PLL, if any in opposition to proliferative aggressive cancer cell MDA-MB-231 both 2D and-3D cell culture conditions. Furthermore, PLL was administered in B16F10 murine melanoma cells induced BALB/c mice model. The study has been designed through transcription and translation level of PLL-induced tumor-angiogenesis and apoptotic gene-expression modulation level and various relevant histological studies in comparison with untreated control. Studies have shown anti-proliferative and anti-tumor angiogenic efficacy of PLL better in in-vitro 3D tumor-microenvironment against MDA-MB-231 breast cancer cells. Furthermore, in-vivo model, PLL was found to suppress tumorigenesis process at minimum dose. PLL found to induce apoptosis through-upregulation of cytosolic-cytochrome-C, caspase-3 and PARP activations when administered in B16F10 induced in-vivo tumor. In blocking proliferation and tumor-angiogenesis, PLL was found to be effective as it significantly downregulated activity of VEGF, VEGFR2, Ki-67 and c-Myc expression. As PLL blocked tumor progression and induced DNA-break, also upregulated apoptotic process and recovered tissue architecture as revealed from histological study in comparison with untreated control. Overall PLL was found to be a promising anti-tumor angiogenic and anti-proliferative drug that was effective both in in-vitro breast cancer 3D tumor-microenvironment and in-vivo metastatic-mice-model.

Dataset concerning effects of stevia (Stevia rebaudiana bertoni), amlodipine, losartan, and valsartan on water consumption, blood glucose and heart tissue in gentamycin-induced nephrotoxicity in the rat model.

This dataset indicates the effect of stevia (Stevia rebaudiana Bertoni); angiotensin-II type-1 receptor (AT1) blockers, losartan and valsartan; and a calcium (Ca2+) channel blocker, amlodipine; on water consumption, fasting blood glucose, and cardiac histology in gentamycin-induced nephrotoxic rat model. Six groups of male Sprague-Dawley rats were selected as sham control group, gentamycin-induced nephrotoxic disease control group; gentamycin-induced disease control groups treated with stevia (200 mg/kg/day); amlodipine (4 mg/kg/day); losartan (15 mg/kg/day) and valsartan (5 mg/kg/day) respectively. Fasting blood glucose level and water consumption were recorded daily for the first week and then weekly for the rest of treatment period. Serum creatinine, blood urea, total protein and lipid profile were determined. Histological examination of the heart tissue was assessed to find out any alteration of cardiac muscle tissue following gentamycin-induced nephrotoxicity. This article provides additional data collected from the same animals previously reported [1] .

In-vitro and in-vivo evaluation of polymeric microsphere formulation for colon targeted delivery of 5-fluorouracil using biocompatible natural gum katira.

The aim was to develop oral site-specific rate-controlled anticancer drug delivery to pacify systemic side-effects and offer effective and safe therapy for colon cancer with compressed dose and duration of treatment. The double emulsion solvent evaporation method was employed. To check functionality, DAPI-staining and in-vivo anticancer study of Ehrlich Ascites Carcinoma bearing mice was tested. Histopathology of liver and kidney and Cell morphology of EAC cell was also performed. Formulated and optimized polymeric microsphere of 5-FU showed excellent physicochemical features. In-vitro, DAPI results pointed drug-treated groups displayed the prominent feature of apoptosis. The percentage of apoptotic of entrapped drug played in a dose-dependent manner. Significant decreases in EAC liquid tumors and increased life span of treated mice were observed. Rate of variation of cell morphology was more in 5-FU loaded microsphere than 5-FU injection. Hematological and biochemical parameter's and Histopathology of liver and kidney resulted that due to control released formulation have slow release rate, that gives less trace on liver and kidney function. Finally, we foresee that polymeric microsphere of 5-FU applying natural gum katira could be an assuring micro-carrier for active colon targeting delivery tool with augmented chemotherapeutic efficacy and lowering side effect against colon cancer.

Renoprotective effects of stevia (Stevia rebaudiana Bertoni), amlodipine, valsartan, and losartan in gentamycin-induced nephrotoxicity in the rat model: Biochemical, hematological and histological approaches.

The current study investigated the renoprotective effects of stevia, angiotensin-II type 1 receptor (AT1) blocker and calcium (Ca2+) channel blocker in gentamycin-induced nephrotoxicity in rat models. Six groups of male Sprague-Dawley rats of eight weeks old were taken for the experiment: sham control, nephrotoxicity, treatment with amlodipine (4 mg/kg/day); stevia (200 mg/kg/day); losartan (15 mg/kg/day) and valsartan (5 mg/kg/day), accordingly. The blood sample was taken for the assessment of renal and hepatic-functional variables like serum creatinine, blood urea, BUN and SGPT, SGOT, and total serum bilirubin. Hematological parameters were also examined. Histological examination has been done on kidneys and liver. Alterations of the body weight and the organ's weight were documented. Treatment with stevia and valsartan significantly decreased serum creatinine levels. A reduction of liver enzymes, and total serum bilirubin levels were observed in all the treatment groups. Treatment with valsartan and amlodipine, remarkably and stevia, mildly reduced the renal tissue damage, inflammation, and tubular necrosis. However, the present study demonstrated that losartan treatment aggravated kidney damage by increasing protein cast, calcification, tubular necrosis, and injury. This comparison indicated that both stevia and valsartan have beneficial renoprotective effect and valsartan offers a better treatment option in renal damage over losartan.

Polymeric Microsphere Formulation for Colon Targeted Delivery of 5-Fluorouracil Using Biocompatible Natural Gum Katira.

Controlled release delivery system of chemotherapeutic agents at the site of colon endorses modern drug-entrapped delivery tools, which release the entrappedagents at a controlled rate for anextended period providing patient compliance and additional protection from the degradinggastric environment. Thus, the present study was aimed to develop and optimize a novel polymeric microsphere of 5-fluorouracil (5-FU) using natural gum katira to obtain an optimal therapeutic response at the colon. Due course of experimentation, in-vivo safety profile of the gum katira in an animal model was established. Modified solvent extraction/evaporation technique wasemployed to encapsulate 5-FU in the natural polymeric microsphere and was characterized using in-vitro studies to investigate particle size, morphology, encapsulation efficiency and release of the drug from developed formulation. Formulated and optimized polymeric microsphere of 5-FU using gum katira polymer own optimal physicochemical characteristics with a fine spherical particle with size ranged from 210.37±7.50 to 314.45±7.80 µm.Targeted microsphere exhibited good cytotoxicity and also has high drug entrapment efficiency, and satisfactory release pattern of the drug within a time frame of 12 h. Finally, we foresee that the optimized polymeric gum katiramicrosphere of 5-FU could be a promising micro-carrier for efficient colon drug targeting delivery tool with improved chemotherapeutic efficacy against colon cancer.

Preliminary analysis of the effect of Stevia (Stevia rebaudiana) in patients with chronic kidney disease (stage I to stage III).

BACKGROUND: Stevia, Stevia rebaudiana (Bertoni), has become an important economic plant for its commercial use as a sweetener. Stevia plays a significant role in the healthcare practice of different cultures and in population. Previous animal and clinical studies demonstrated the efficacy of Stevia against chronic diseases like diabetes and hypertension. This study aimed to investigate the beneficial effect of Stevia in chronic kidney disease (CKD) patients after three (3) months of treatment along with the conventional antihypertensive and anti diabetic medications. METHODS: A prospective, interventional, randomized, single-blind, placebo-controlled trial has been done with 97 participants. Stevia capsule (250 mg) or matching placebo was given to the participants twice daily along with Angiotensin-II Receptor Blocker (ARB) and/or Ca2+ Channel Blocker (CCB). First follow up visits were done after 3 months of the interval. Blood and urine samples were collected for the biochemical tests. A structured questionnaire was used for the baseline assessment. Informed consent was taken from each participant. RESULTS: Both hypertension and diabetes were found to be associated with CKD. Most of the participants (52.3%) of Stevia group were in CKD Stage II. Significant changes were found in Serum creatinine (p < 0.027), Serum Uric acid (p < 0.009), Fasting blood sugar (p < 0.041) and Postprandial blood sugar (p < 0.013) and Microalbumin (p < 0.041) level in the treatment group. CONCLUSION: The initial result demonstrated that Stevia has the potential for a significant improvement of some biochemical parameters in CKD patients. After completion of the nine (9) months clinical trial, the constructive effect of Stevia can be confirmed in this group of patients.

Induction of apoptosis, anti-proliferation, tumor-angiogenic suppression and down-regulation of Dalton's Ascitic Lymphoma (DAL) induced tumorigenesis by poly-l-lysine: A mechanistic study.

PURPOSE: The present study, attempts to validate the molecular mechanism(s) of Poly-l-lysine (PLL) induced apoptosis, anti-proliferative and anti-tumorigenic properties in in-vitro HUVECs cells and Dalton's Ascitic Lymphoma (DAL) and in in-vivo DAL cell bearing BALB/c mice model. MATERIALS AND METHODS: The cell proliferation assay and morphological assay was carried out using the MTT assay and Giemsa staining method. The antitumor activity of PLL was evaluated in BALB/c mice at 20 and 40 mg/kg/b.w doses for 21 days for DAL solid tumor model. Several tumor evaluation endpoints, hematological and biochemical parameters were estimated. Additionally, the tumor apoptosis, anti-proliferative and anti-tumor angiogenesis effects were assessed using western blots and immunohistochemistry. RESULTS: PLL significantly decreased cell proliferation in in-vitro HUVECs and DAL cells without significant effects on normal cell growth. PLL also induced alteration in cellular morphology in DAL cells. Therafter, in the BALB/c mouse model, PLL had noticeable inhibition in DAL-induced tumorigenesis. This inhibition was evident through reduced solid tumor volume and weight versus the control group. However, PLL promoted tumor apoptosis and suppressed cell-proliferation and tumor-angiogenesis. PLL also increased hematological markers significantly compared to 5-flurouracil (5-FU). The amount of TdT in the nuclei of DAL cells in mice treated with PLL was significantly increased while in contrast decreases of anti-apoptotic protein Bcl-2 expression were observed. PLL also significantly upregulated the pro-apoptotic protein Bax and activated caspase-3. Measurable decreases of cyclin-D1 were observed through PLL treatments, an indicator of cell-cycle arrest. These studies also indicate PLL's induction and anti-proliferative effects through suppression of the c-Myc and Ki-67 proliferation-indices. Additionally, PLL inhibited tumor-angiogenesis through suppression of VEGF and CD34 protein expression levels and reduction ofmicrovesseldensityversus similar parameters in tumors from control mice. CONCLUSION: The present study offers opportunities and hopes for possible anti-tumortherapies with PLL in the near future and warrants further formulation developments.

Poly-L-Lysine Inhibits Tumor Angiogenesis and Induces Apoptosis in Ehrlich Ascites Carcinoma and in Sarcoma S-180 Tumor

Background: This study focuses on the role of Poly-L-lysine (PLL), an essential amino acid, on molecular changes of tumor angiogenesis suppression, pro-apoptotic and anti-apoptotic gene expression after treatment on Ehrlich ascites carcinoma (EAC) and solid sarcoma-180 tumor cells bearing mice. Materials and Methods: The cell viability was carried out using MTT assay. The antitumor activity was evaluated by treatment with PLL at 20 and 40mg/kg/b.w doses for 14 days in EAC ascites tumor and 21 days for Sarcoma-180 solid tumor model. Several tumor evaluation studies, haematological and biochemical parameters were estimated. Importantly, the tumor cell apoptosis was assessed using microscopic observations, DNA fragmentation assay, Flow cytometric analysis, cell-cycle and electron-microscopic study, following which, the expression of several signal proteins related to pro-apoptosis, anti-apoptosis and tumor angiogenesis were quantified using western blotting and immunohistochemistry study. Results: Precisely, PLL had cytotoxic effect on K562; A549; U937 and B16F10 cancer cells. Significant decreases in liquid and solid tumors and increased life span of treated mice were observed (P<0.05). Typical morphological changes, apoptosis bleb phenomenon and sub-G1 cell cycle arrests revealed that PLL promoted apoptotic cell death. Western blot and immunohistochemistry confirms, PLL activated apoptotic signalling cascades through down regulation of Bcl-2 and CD31 protein and upregulation of Bax and p53 proteins. The anti-angiogenic effects were also accompanied with decreased VEGF expression and reduced peritoneal-angiogenesis and microvessel density. Conclusions: The antitumor and antitumor-angiogenic activity of PLL was confirmed from all the results via up and down regulation of relevant signal proteins reported in this publication.

Pharmacological and toxicological investigations of etodolac loaded gum katira microspheres prepared by W1/O/W2 emulsion solvent evaporation technique in rats

ABSTRACT Etodolac is a non-steroidal anti-inflammatory drug (NSAID) and approved by USFDA as a COX2 inhibitor. Although etodolac therapy provides clinical benefits, it is associated with upper gastrointestinal (GI) tract complications also. Etodolac loaded gum Katira microsphere (ELGKM) was prepared by W1/O/W2 emulsion solvent evaporation technique. The gastric irritation properties of orally administered pure etodolac, ELGKM and blank microspheres (without etodolac) were evaluated in experimental rats treated for 6 days. The stomach examination and biochemical investigation of stomach tissue of treated rats indicated that ELGKM formulation remarkably reduced ulcerogenecity as compared to pure etodolac. The anti-inflammatory activities of pure etodolac and ELGKMs were ascertained by the implantation of cotton pellets in rats for 6 days. Based on the results, ELGKMs showed significant anti-inflammatory activities (P<0.01) as compared to control group. The cotton pellets test suggested that ELGKM formulation retained more anti-inflammatory properties among the groups. The hematological changes, biochemical analysis and histopathological studies of subacute toxicity in rats revealed that ELGKM were the effective sustained release formulation in the treatment of chronic pain and inflammation. In conclusion, the physicochemical characterization, pharmacological and toxicological studies suggest that ELGKMs may represent as a potential candidate for sustained drug delivery (10-12 hours) in chronic joint pain related diseases with remarkably diminished gastrointestinal side effects.

An evaluation of knowledge, attitude, and practice of institutional ethics committee members from eastern India regarding ethics committee functioning and pharmacovigilance activities conducted during clinical trials: A pilot study.

PURPOSE OF STUDY: The vital responsibility of Institutional Ethics Committee (IEC) members is to ensure the safety of the subjects participating in clinical trials. Hence, it is essential for IEC members to be aware of the common pharmacovigilance strategies followed during clinical trials. However, the information about the knowledge, attitude, and practice of IEC members regarding the pharmacovigilance activities followed during clinical trials is scarce worldwide, especially in India. Hence, this cross-sectional study was designed to assess the knowledge, attitude, and practice of IEC members of 10 hospitals of Kolkata, India. MATERIALS AND METHODS: A cross-sectional study using a self-administered, validated questionnaire was conducted among 10 hospitals (five government and five corporate hospitals) in Kolkata conducting active clinical research and having functional Ethics Committees (ECs) in the month of September-November, 2012. An IEC approval was taken for this study. Two reminders were given to all EC members through telephone/e-mail for completion and returning of the forms. The filled in forms were returned to their respective Member Secretaries, from whom authors' collected the forms. Data were analyzed using SPSS version 16.0 software and MS-Excel 2007. Categorical data were analyzed using Chi-square test and a P < 0.05 was considered statistically significant. RESULTS: Out of the 100 distributed questionnaires, 40 were returned of which 10 were not filled properly. Overall awareness regarding different pharmacovigilance terminologies and activities among EC members from nonmedical background (71.43%) was found to be more than that of the medical members (68.75%), though the figure was not statistically significant. Majority of the members (75%) felt that EC should decide compensation in case of a serious adverse event. CONCLUSION: The present study signifies that there is a low level of awareness in IEC members of Kolkata regarding pharmacovigilance activities conducted during clinical trials; and, hence the functioning of the ECs to safeguard the safety of patients during clinical trials remains questionable. There is a definite need for immediate intervention in the form of mandatory training hours for EC members about pharmacovigilance activities and reporting timelines to ensure clinical trial subject safety in the long run.

Pharmacophore modeling and 3D quantitative structure-activity relationship analysis of febrifugine analogues as potent antimalarial agent.

Febrifugine and its derivatives are effective against Plasmodium falciparum. Using PHASE algorithm, a five-point pharmacophore model with two hydrogen bond acceptor (A), one positively ionizable (P) and two aromatic rings (R), was developed to derive a predictive ligand-based statistically significant 3D-quantitative structure-activity relationship (QSAR) model (r(2) = 0.972, SD = 0.3, F = 173.4, Q(2) = 0.712, RMSE = 0.3, Person-R = 0.94, and r(2) pred = 0.8) to explicate the structural attributes crucial for antimalarial activity. The developed pharmacophore model and 3D QSAR model can be a substantial tool for virtual screening and related antimalarial drug discovery research.

Antihyperlipidemic Activity of the Ethyl-acetate Fraction of Stereospermum Suaveolens in Streptozotocin-induced Diabetic Rats.

OBJECTIVES: Dyslipidemia in diabetes mellitus is a significant risk factor for the development of cardiovascular complications. The aim of this study was to evaluate the effect of the ethyl-acetate fraction of an ethanolic extract from Streospermum suaveolens on lipid metabolism in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced by intraperitonial injection of STZ (50 mg/kg). Diabetic rats were treated with an ethyl-acetate fraction orally at doses of 200 and 400 mg/kg daily for 14 days. On the 15(th) day, serum lipid profiles, such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), were estimated in experimental rats. The atherogenic (AI) and the coronary risk (CRI) indices were also evaluated. RESULTS: The ethyl-acetate fraction at doses of 200 and 400 mg/kg significantly (P< 0.001) and dose-dependently reduced serum cholesterol, triglycerides and LDL, but increased HDL towards near normal levels as compared to diabetic control rats. The fraction also significantly (P< 0.001) lowered the atherogenic index (AI) and coronary risk index (CAI) in a dose-dependent manner. CONCLUSION: The present study demonstrated that the ethyl-acetate fraction of Stereospermum suaveolens exhibits a potent antihyperlipidemic activity in hyperglycemic rats and suggests that the plant may have therapeutic value in treating the diabetic complication of hyperlipidemia.

Protective Effect of Ethyl Acetate Fraction of Stereospermum Suaveolens Against Hepatic Oxidative Stress in STZ Diabetic Rats.

Stereospermum suaveolens is a folk remedy for the treatment of diabetes and liver disorders in southern parts of India. In the present study, the protective effect of the ethyl acetate fraction of ethanol extract from S. suaveolens against hepatic oxidative stress was evaluated in streptozotocin (STZ)-induced diabetic rats for 14 days. The ethyl acetate fraction was administered orally to the STZ diabetic rats at the doses of 200 and 400 mg/kg. Blood glucose level was measured according to glucose oxidase method. In order to determine hepatoprotective activity, changes in the levels of serum biomarker enzymes such as aspartate transaminase (AST), alanine transaminase (ALT), and serum alkaline phosphatase (SALP) were assessed in the ethyl acetate fraction treated diabetic rats and were compared with the levels in diabetic control rats. In addition, the antioxidant activity of ethyl acetate fraction was evaluated using various hepatic parameters such as thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). It was found that administration of ethyl acetate fraction (200 and 400 mg/kg) produced a significant (P < 0.001) fall in fasting blood glucose level, TBARS, bilirubin, AST, ALT, and SALP, while elevating the GSH levels, and SOD and CAT activities in diabetic rats. Histopathologic studies also revealed the protective effect of ethyl acetate fraction on the liver tissues of diabetic rats. It was concluded from this study that the ethyl acetate fraction from ethanol extract of S. suaveolens modulates the activity of enzymatic and nonenzymatic antioxidants and enhances the defense against hepatic oxidative stress in STZ-induced diabetic rats.

Effect of potent ethyl acetate fraction of Stereospermum suaveolens extract in streptozotocin-induced diabetic rats.

To evaluate the antihyperglycemic effect of ethyl acetate fraction of ethanol extract of Stereospermum suaveolens in streptozotocin-(STZ-) induced diabetic rats by acute and subacute models. In this paper, various fractions of ethanol extract of Stereospermum suaveolens were prepared and their effects on blood glucose levels in STZ-induced diabetic rats were studied after a single oral administration (200 mg/kg). Administration of the ethyl acetate fraction at 200 mg/kg once daily for 14 days to STZ-induced diabetic rats was also carried out. The parameters such as the fasting blood glucose, hepatic glycogen content, and pancreatic antioxidant levels were monitored. In the acute study, the ethyl acetate fraction is the most potent in reducing the fasting serum glucose levels of the STZ-induced diabetic rats. The 14-day repeated oral administration of the ethyl acetate fraction significantly reduced the fasting blood glucose and pancreatic TBARS level and significantly increased the liver glycogen, pancreatic superoxide dismutase, and catalase activities as well as reduced glutathione levels. The histopathological studies during the subacute treatment have been shown to ameliorate the STZ-induced histological damage of pancreas. This paper concludes that the ethyl acetate fraction from ethanol extract of Stereospermum suaveolens possesses potent antihyperglycemic and antioxidant properties, thereby substantiating the use of plant in the indigenous system of medicine.

Anti-inflammatory effect of Stereospermum suaveolens ethanol extract in rats.

The anti-inflammatory effect of the ethanol extract of Stereospermum suaveolens (Roxb.) DC (Bignoniaceae) bark given orally at the dose of 200 and 400 mg/kg body weight was studied in rats using the carrageenan-, dextran-, and histamine-induced hind paw edema, and cotton pellet-induced granuloma formation models. Indomethcin at the dose of 10 mg/kg body weight was used as a standard drug. The extract (400 mg/kg body weight per os) showed maximum inhibition of edema 64.6, 53.48, and 50.06% at the end of 3 h with carrageenan-, dextran-, and histamine-induced rat paw edema, respectively. The extract (400 mg/kg) exhibited significant reduction (34.77%) in granuloma weight in the cotton pellet-induced granuloma model. From these results it could be concluded that, the ethanol extract of Stereospermum suaveolens possesses maximum anti-inflammatory activity in a dose-dependent manner, in various experimental models.

Synthesis and antimalarial evaluation of some 4-quinazolinone derivatives based on febrifugine.

A series of 2-substituted and 2,3-substituted quinazolin -4(3H)-one derivatives were designed and synthesized based on the structure of febrifugine. The structures of the new compounds were confirmed by spectral analysis. The in vivo biological activity test results indicated that those compounds exhibited antimalarial activities against Plasmodium berghei in mice, at a dose of 5 mg/kg. Compared to Chloroquine and Artemisinin, these compounds have the advantages of shorter synthetic routes and consequently are highly cost effective in nature.

Antihyperglycemic and antioxidant activities of medicinal plant Stereospermum suaveolens in streptozotocin-induced diabetic rats.

The ethanol extract of Stereospermum suaveolens (EESS) bark was evaluated for its antihyperglycemic in addition to antioxidant effects in streptozotocin (STZ)-induced diabetic rats by acute and subacute models at dose levels of 200 and 400 mg/kg body weight, given orally. The ethanol extract showed a significant reduction in fasting blood glucose levels when compared to the standard drug, oral Glibenclamide (0.5 mg/kg body weight). The serum of rats treated with ethanol extract showed decreased levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, bilirubin, creatinine, urea, total cholesterol, triglycerides, and increased level of total proteins. EESS showed reduction in thiobarbituric acid reactive substances level and significantly increased the body weight (P < .001), glycogen, reduced glutathione, superoxide dismutase, and catalase activities, compared with STZ diabetic control in a dose-dependent manner. This finding shows that the ethanol extract of Stereospermum suaveolens exhibits potent antihyperglycemic and antioxidant properties.

In vitro and in vivo antimicrobial action of tea: the commonest beverage of Asia.

The methanolic extract of leaves of Camellia sinensis (L) O. KUNTZE was screened for antimicrobial property against 111 bacteria comprising 2 genera of Gram positive and 7 genera of Gram negative bacteria. Most of these strains were inhibited by the compound at 10-50 microg/ml level and few strains were sensitive even at lower concentrations (5 microg/ml). The bacteria could be arranged in the decreasing order of sensitivity towards the compound in the following manner: Staphylococcus aureus, Vibrio cholerae, Escherichia coli, Shigella spp., Salmonella spp., Bacillus spp., Klebsiella spp. and Pseudomonas aeruginosa. The antibacterial activity of compound could also be confirmed in vivo. When it was given to Swiss strain of white mice at different dosages (30, 60 microg/mouse), it could significantly protect the animals challenged with 50 MLD of Salmonella typhimurium NCTC 74. According to Chi square test the in vivo data were highly significant (p<0.001).

Targeting of mannosylated liposome incorporated benzyl derivative of Penicillium nigricans derived compound MT81 to reticuloendothelial systems for the treatment of visceral leishmaniasis.

The antileishmanial property of a Benzyl derivative of a new antibiotic MT81 (Bz2MT81), isolated and purified from a fungal strain of Penicillium nigricans NRRL 917 was tested in free, liposome intercalated and mannose coated liposome intercalated forms in vivo against visceral leishmaniasis in hamsters. Mannose grafted liposome intercalated Bz2MT81 eliminated intracellular amastigotes of Leishmania donovani within splenic macrophages more efficiently than the liposome intercalated Bz2MT81 or free Bz2MT81. At a dose equivalent to 7.5 microg/Kg body weight when injected subcutaneously (s.c) in mannose grafted liposome intercalated form for 15 days in an interval of three days, the splenic parasitic load decreased to the extent of 79.1% of the total parasite present in infected control animals. Whereas, an identical amount (7.5 mug/Kg body weight) of Bz2MT81 in free or liposome intercalated form was found less effective in controlling the parasite in spleen (in free Bz2MT81 form, suppression of parasitic load is 49.8% and in liposome intercalated form, it is 55.1%). Both mannosylated liposomes and Bz2MT81 were noted non-toxic to the host peritoneal macrophages. Histological examinations of spleen and liver, kidney function tests (SGPT, alkaline phosphatase, creatinine and urea in blood plasma) showed that the toxicity of Bz2MT81 was reduced up to normal level when mannose grafted liposomal Bz2MT81 were administered.