Mouse spermatogonia exposed to a high,multiply fractionated dose of a cancer chemotherapeutic drug: Mutation analysis by electrophoresis

Male mice of the DBA/2J strain were injected with procarbazine at a dose of 200 mg/kg body weight twice weekly until an accumulated dose of 2400 mg/kg was reached. A concurrent control group, injected only with the vehicle (saline) was also established. Most of the treated animals died as a result of exposure and all survivors became temporarily sterile. After regaining fertility the few survivors were repeatedly mated with C57BL/6J females over several weeks time to generate a population of F₁ animals. The parental animals and the F₁ were subsequently analyzed by electrophoresis for the occurence of newly arisen mutations of spermatogonial origin. A mutation in the gene Pep-3 was found.     

Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part II: Identification of 4-ethylamino-3-(2-hydroxyethoxy)-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide and its biological evaluation

The continuing investigation of SAR studies of 3-(2-hydroxyethoxy)-N-(5-benzylthiazol-2-yl)-benzamides as stearoyl-CoA desaturase-1 (SCD-1) inhibitors is reported. Our prior hit-to-lead effort resulted in the identification of 1a as a potent and orally efficacious SCD-1 inhibitor. Further optimization of the structural motif resulted in the identification of 4-ethylamino-3-(2-hydroxyethoxy)-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (37c) with sub nano molar IC₅₀ in both murine and human SCD-1 inhibitory assays. This compound demonstrated a dose-dependent decrease in the plasma desaturation index in C57BL/6J mice on a non-fat diet after 7 days of oral administration.     

Comparative metabolism of the cis and trans isomers of N-nitroso-2-6-dimethylmorpholine in rats,hamsters and guinea pigs

The in vivo metabolism of the cis and trans isomers of N-[3,5-³H] nitroso-2,6-dimethylmorpholine (NDMM) was studied in female Fischer rats, Syrian golden hamsters and guinea pigs by analysis of urinary metabolites using high pressure liquid chromatography (HPLC). Animals were treated by gavage with 12 mg/kg body wt. of NDMM, composed of both isomers and 12 μCi/kg body wt. of either of the separated radioactive isomers (cis or trans). Control animals received 12 mg, 12 μCi/kg body wt. NDMM with both isomers labeled in their natural proportion.There was a substantial increase in the excretion of a particular metabolite, 2-(2-hydroxyl-methyl)ethoxy propanoic acid, in the urine of rats, hamsters and guinea pigs 24 h after received the trans isomer (24, 22 and 13% of the total dose excreted, respectively). A minor metabolite was determined to be 2,6-dimethylmorpholine-3-one, another product of α-oxidation. The metabolite 1-amino-2-hydroxypropanol was identified, indicating that NDMM was metabolized by both α-and β-oxidation.In all three species, animals administered the cis isomer excreted larger amounts of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) and N-nitroso-bis(2-hydroxypropyl)amine (BHP) products of beta oxidation, than those treated with the trans isomer. Hamsters and guinea pigs treated with the more carcinogenic cis isomer in these species, also excreted twice as much of two other metabolites than was found in the urine of animals given the trans isomer.The trans isomer of NDMM appeared to be preferentially metabolized by α-oxidation and from earlier studies this metabolic pathway seemed to be important in carcinogenesis by NDMM in the rat. The cis isomer might be in a conformation more favorable for β-oxidation and this pathway may be of primary importance in carcinogenesis by NDMM in hamsters and guinea pigs.     

Antidiabetic potential of Caralluma europaea against alloxan-induced diabetes in mice

Medicinal plants play an important role in the management of diabetes mellitus especially in developing countries where resources are lacking. Herbal of natural origin, unlike the synthetic compounds, are more effective, safer and have less side effects. For continuing research on biological properties of Moroccan medicinal plants, the present work was undertaken to evaluate the potential and mechanism of the antidiabetic activity of the Caralluma europaea methanolic extract in alloxan-induced diabetic mice. A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phenolic compounds in the methanolic extract. The in vitro antioxidant property was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging method, reducing power and ß-carotene-linoleic acid assays. The acute toxicity of the extract was evaluated by giving it orally to mice at single doses of 200, 500, 1000, 2000 mg/kg body weight. The antidiabetic effect was conducted on Swiss albino mice. Diabetes was induced with single intraperitonial injection of alloxan monohydrate (200 mg/kg body weight) and animals were treated with methanol extract at a dose of 250 mg/kg and 500 mg/kg body weight. The blood glucose levels were measured and histopathological analysis of pancreas was performed to evaluate alloxan-induced tissue injuries. The main phenols identified and quantified in the extract were ferulic acid, quercetine, 3,4 dihydroxybenzoic acid, rutin, epigallocatechin, and catechin. Ferulic acid was found to be the main phenolic compound ant its proportion was up to 52% of total phenolic compounds, followed by quercetin (36%). The result showed that methanol extract exhibited an antioxidant effect. Acute toxicity studies revealed that C. europaea extract was safe up 2000 mg/kg body weight and approximate LD₅₀ is more than 2000 mg/kg. Moreover, the methanol extract prevented the diabetogenic effect of alloxan and decreased significantly the blood glucose level (P < 0.001) in treated mice. Morphometric study of pancreas revealed that C. europaea extract protected significantly the islets of Langerhans against alloxan-induced tissue alterations.     

Leishmania donovani: Therapeutic and prophylactic action of antimony dextran glycoside (RL-712) in the golden hamster

Antimony dextran glycoside (RL-712, manufactured by Rosco A/S Pharmaceutical Taastrup, Denmark) produced a remarkable decrease in Leishmania donovani densities in hamster spleen and liver when administered in a single intraperitoneal (ip) dose of 500 mg Sb/kg body weight or in 600 mg Sb/kg body weight divided into two or three equal parts injected at weekly intervals beginning 15 days after intracardial inoculation of 10 million amastigotes, and also in a single ip dose of 300 mg Sb/kg body weight 14, 7, and 0 days before intracardial inoculation of 10 million amastigotes. No parasites were detected on using a single dose of 500 mg Sb/kg body weight followed by 100 mg Sb/kg body weight one week later.When the drug was administered in a dose of 500 mg Sb/kg body weight either 10 days before subcutaneous inoculation of 60 million promastigotes or eight days before intracardial inoculation of five million promastigotes, no parasites were recovered by smear or culture from the spleen and liver.Results show the prophylactic and therapeutic actions of this drug against L. donovani in the hamster.     

Safety,Pharmacokinetic, and Efficacy Studies of Oral DB868 in a First Stage Vervet Monkey Model of Human African Trypanosomiasis

There are no oral drugs for human African trypanosomiasis (HAT, sleeping sickness). A successful oral drug would have the potential to reduce or eliminate the need for patient hospitalization, thus reducing healthcare costs of HAT. The development of oral medications is a key objective of the Consortium for Parasitic Drug Development (CPDD). In this study, we investigated the safety, pharmacokinetics, and efficacy of a new orally administered CPDD diamidine prodrug, 2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868; CPD-007-10), in the vervet monkey model of first stage HAT. DB868 was well tolerated at a dose up to 30 mg/kg/day for 10 days, a cumulative dose of 300 mg/kg. Mean plasma levels of biomarkers indicative of liver injury (alanine aminotransferase, aspartate aminotransferase) were not significantly altered by drug administration. In addition, no kidney-mediated alterations in creatinine and urea concentrations were detected. Pharmacokinetic analysis of plasma confirmed that DB868 was orally available and was converted to the active compound DB829 in both uninfected and infected monkeys. Treatment of infected monkeys with DB868 began 7 days post-infection. In the infected monkeys, DB829 attained a median C_max (dosing regimen) that was 12-fold (3 mg/kg/day for 7 days), 15-fold (10 mg/kg/day for 7 days), and 31-fold (20 mg/kg/day for 5 days) greater than the IC₅₀ (14 nmol/L) against T. b. rhodesiense STIB900. DB868 cured all infected monkeys, even at the lowest dose tested. In conclusion, oral DB868 cured monkeys with first stage HAT at a cumulative dose 14-fold lower than the maximum tolerated dose and should be considered a lead preclinical candidate in efforts to develop a safe, short course (5–7 days), oral regimen for first stage HAT.     

Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide

A series of structurally novel stearoyl-CoA desaturase-1 (SCD-1) inhibitors has been identified by optimizing a hit from our corporate library. Preliminary structure–activity relationship (SAR) studies led to the discovery of the highly potent and orally bioavailable thiazole-based SCD-1 inhibitor, 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (23a).     

New potent antifungal triazole alcohols containing N-benzylpiperazine carbodithioate moiety: Synthesis,in vitro evaluation and in silico study

A number of 1H-1,2,4-triazole alcohols containing N-(halobenzyl)piperazine carbodithioate moiety have been designed and synthesized as potent antifungal agents. In vitro bioassays against different Candida species including C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis revealed that the N-(4-chlorobenzyl) derivative (6b) with MIC values of 0.063–0.5 µg/mL had the best profile of activity, being 4–32 times more potent than fluconazole. Docking simulation studies confirmed the better fitting of compound 6b in the active site of lanosterol 14α-demethylase (CYP51) enzyme, the main target of azole antifungals. Particularly, the potential of compound 6b against fluconazole-resistant isolates along with its minimal toxicity against human erythrocytes and HepG2 cells make this prototype compound as a good lead for discovery of potent and safe antifungal agents.     

Testicular Histomorphometry and Ultrastructure of Rats Treated with Cadmium and Ginkgo biloba

The aim of this study is to investigate the association of a single low dose of Cd and daily doses of Ginkgo biloba extract (GbE) on the testis and accessory glands of rats. The animals were treated with a single dose of 3 µmol/kg body weight of cadmium chloride (CdCl₂) and/or 100 mg/kg body weight of GbE. The plasma testosterone levels; corporal, testicular, and accessory glands weight; gonadosomatic index, volumetric proportion; and absolute volume of testicular components did not change after the treatments. CdCl₂ caused significant reduction in Leydig cells volume and altered Leydig cell morphology, as well as vacuolated Sertoli cells cytoplasm, irregular chromatin condensation of late spermatids, and modified acrosome formation. However, animals that received GbE did not show these alterations. The reversal of Cd-induced alterations by the extract is a strong indication that G. biloba is helpful in diminishing the effect of Cd toxicity.     

Toxicity profiling of the ethanolic extract of Citrullus lanatus seed in rats: behavioral,biochemical and histopathological aspects

Citrullus lanatus (Cucurbitaceae) is conventionally used for the treatment of urinary tract infection, renal stones, hypertension, diabetes and diarrhoea. Current study evaluates acute and 28 days repeated toxicity ethanolic extract of C. lanatus seed (EECLS) in Wistar rats to measure its safety profile. The single dose (2000 mg/kg BW) of EECLS was administered while in 28 days repeated study 250, 500 and 1000 mg/kg BW were administered orally in rats. Parameters such as biochemical, haematological and histopathological were analysed in subacute toxicity study. During study, no apparent sign of toxicity, behavioural changes and mortality were detected in acutely exposed animals. In 28 days repeated toxicity study, rats did not show significant changes in behaviour, gross pathology, body weight, biochemical and haematological parameters. Abridged serum glucose and cholesterol levels during the study designate their roles in treatment of hyperglycaemic and hyperlipidaemic conditions. No significant difference was observed in histopathology of liver and kidneys of treated rats. The current investigation demonstrated that EECLS is non-toxic below 1000 mg/kg BW and provides protection to some body organs. The data propose that LD₅₀ of EECLS was greater than 2000 mg/kg BW and the no observed adverse effect level (NOAEL) of EECLS was at the dose of 1000 mg/kg in rats. Taken together, our finding suggests that, EECLS is safe and provides some protection to body organs; also, its extract can be used for further preclinical and clinical evaluation for its therapeutic activity.     

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection

BackgroundOne of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice.Methodology/Principal findingsTwo months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56^th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-β gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2.Conclusion/SignificanceThis study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.     

The effect of active hexose correlated compound in modulating cytosine arabinoside-induced hair loss,and 6-mercaptopurine- and methotrexate-induced liver injury in rodents

Background: Active hexose correlated compound (AHCC) (a mixture of polysaccharides, amino acids, lipids and minerals derived from cultured mycelia of a Basidiomycete mushroom, Lentinula edodes) was used to assess amelioration of alopecia (hair loss) caused by cytosine arabinoside (Ara-C) and modulation of liver injury caused by single doses 6-mercaptopurine (6-MP) plus methotrexate (MTX). Methods: Follicular integrity and hair growth was assessed in male and female SD neonatal rats (8 days old) treated with a single dose of Ara-C (30 mg/kg/day, i.p.) and AHCC (500 mg/kg/day, p.o.) for 7 consecutive days. The side effects of a single oral dose of 6-MP (2.5 mg/kg body weight) plus MTX (30 mg/kg body weight) and their amelioration by treatment with AHCC (1000 mg/kg body weight) for 28 days were assessed in male ddY mice (8 weeks old). Results: Of the Ara-C treated rats 71.4% showed severe alopecia and 28.6% showed moderate alopecia. However, the AHCC (p.o.)-treated Ara-C group was significantly protected from alopecia. Ara-C treated rats had profound loss of hair follicles but the Ara-C plus AHCC-treated group had mild losses of follicles. AHCC supplementation to the 6-MP- and MTX-treated mice significantly increased body weight, erythrocytes, leukocytes and serum albumin, improved liver hypertrophy and degeneration, normalized the activities of serum glutamic oxaloacetic transaminase (sGOT) and serum glutamic pyruvic transaminase (sGPT), and enhanced liver drug-metabolizing enzymes. Conclusion: Co-administration of AHCC significantly reduced the side effects associated with Ara-C, 6-MP and MTX. However, the molecular mechanism for AHCC activity and its clinical integrity for use needs defining.     

Design,physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents

A series of thirty N-(phenoxy)alkyl or N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols has been designed, synthesized and evaluated for anticonvulsant activity in MES, 6 Hz test, and pilocarpine-induced status epilepticus. Among the title compounds, the most promising seems R-(−)-2N-{2-[2-(2,6-dimethylphenoxy)ethoxy]ethyl}aminopropan-1-ol hydrochloride (22a) with proved absolute configuration with X-ray analysis and enantiomeric purity. The compound is effective in MES test with ED₅₀ = 12.92 mg/kg b.w. and its rotarod TD₅₀ = 33.26 mg/kg b.w. The activity dose is also effective in a neurogenic pain model—the formalin test. Within high throughput profile assay, among eighty one targets, the strongest affinity of the compound is observed towards σ receptors and 5-HT transporter and the compound does not bind to hERG. It also does not exhibit mutagenic properties in the Vibrio harveyi test. Moreover, murine liver microsomal assay and pharmacokinetics profile (mice, iv, p.o., ip) indicate that the liver is the primary site of biotransformation of the compound, suggesting that both 22a and its metabolite(s) are active, compensating probably low bioavailability of the parent molecule.     

Comparative efficacy of fluconazole and amphotericin B in the parenteral treatment of experimental paracoccidioidomycosis in the rat

Patients with severe and complicated paracoccidioidomycosis are treated with amphotericin B by the intravenous route. Fluconazole is active in vitro against Paracoccidioides brasiliensis and can also be administered intravenously, but few clinical or experimental data are available about its action against the infection caused by this fungus. In the present study, the efficacy of fluconazole andamphotericin B was assessed comparatively in rats inoculated parenterally with P. brasiliensis. The treatment was performed 3 times a week for 4 weeks starting one week after infection. Fluconazole administered intraperitoneally (14 mg/kg bodyweight/dose) was more effective (P > 0.001)than amphotericin B (2 mg/kg body weight/dose) in reducing the number of colony forming units in the lungs and spleen. When administered intravenously at the dose of 3 mg/kg body weight, fluconazole was as effective as amphotericin B (0.8 mg/kg body weight) in reducing the pulmonary fungal burden. Under these conditions, the rats treated with fluconazole had a smaller number of colony forming units than untreated animals (P > 0.001), but amphotericin B was more effective than fluconazole in reducing spleen infection (P > 0.005). Except for this result obtained with a low dose, fluconazole showed an antifungal action equal to or higher than that of amphotericin B. The activity of fluconazole at doses equivalent to those used for human treatment suggests that this antifungal agent may be an alternative to amphotericin B for the early intravenous treatment of patients with paracoccidioidomycosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Liposomal hamycin in the control of experimental aspergillosis in mice: relative toxicity, therapeutic efficacy and tissue distribution of free and liposomal hamycin.

Therapeutic efficacy of liposomal Hamycin has been evaluated in an animal model system for aspergillosis in Balb/c mice. Hamycin was intercalated into soya phosphatidyl choline (SPC), SPC: choline (1:1, vol./vol.) and DMPC liposomes. A single dose of either 0.1 mg/kg, 0.25 mg/kg or 0.5 mg/kg of liposomal Hamycin and 0.1 mg/kg of free Hamycin was injected (i.v.) into animals infected with Aspergillus fumigatus. An increase in the survival rate of animals along with decrease in fungal count in various organs was observed with liposomal administration. Incorporation of cholesterol into liposomes decreased the in vivo toxicity of Hamycin in a dose dependent manner. However, antifungal activity both in the presence and absence of cholesterol showed marked variation as compared to that of non-aromatic polyenes, e.g. amphotericin B. Analysis of Hamycin distribution by HPLC in various tissues revealed higher blood concentration of this drug, when given in free form, compared to its liposomised form. These studies suggest that liposomal Hamycin is more effective than free Hamycin in controlling the experimental Aspergillosis.     

Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats

The effects of oral administration of aqueous extract of Bulbine natalensis Baker stem at daily doses of 25, 50, and 100 mg/kg body weight on the reproductive function of Wistar rats were evaluated. The indices of mating and fertility success as well as quantal frequency increased after 7 days of treatment in all the dose groups except the 100 mg/kg body weight group. The number of litters was not statistically different (P > 0.05) from the control. Whereas the absolute weights of the epididymis, seminal vesicle, and prostate were not affected, that of the testes was significantly increased. The epididymal sperm count, motility, morphology, and viscosity were not different from the control after 7 days of treatment. The male rat serum testosterone, progesterone, luteinizing hormone, and follicle-stimulating hormone significantly increased in the 25 and 50 mg/kg body weight groups, whereas the estradiol concentration decreased significantly at all the doses. The extract dose of 100 mg/kg body weight decreased the serum testosterone and progesterone levels in male rats. The prolactin concentration was not affected by all the doses. All the indices of reproduction, maternal, embryo/fetotoxic, teratogenic, and reproductive hormones in the female rats were not statistically different from that of their control except the resorption index, which increased at the dose of 100 mg/kg body weight of the extract. Histologic examination of the cross section of rat testes that received the extract at all the doses investigated revealed well-preserved seminiferous tubules with normal amount of stroma, normal population of spermatogenic and supporting cells, as well as normal spermatocytes within the lumen. The results revealed that the aqueous extract of Bulbine natalensis stem at doses of 25 and 50 mg/kg body weight enhanced the success rate of mating and fertility due to increased libido as well as the levels of reproductive hormones in male rats. The absence of alterations in the reproductive parameters of female rats at doses of 25 and 50 mg/kg body weight of Bulbine natalensis stem extract suggest that the extract is “safe” for use at these doses by females during the organogenic period of pregnancy, whereas the extract dose of 100 mg/kg body weight portends a negative effect on some reproductive functions of male and female rats.     

Assessment of pharmacological activities of two medicinal plant of Bangladesh: Launaea sarmentosa and Aegialitis rotundifolia roxb in the management of pain,pyrexia and inflammation

Background

The current study aims at evaluating the analgesic, anti-pyretic and anti-inflammatory properties of methanolic extract of the stem, bark and leaves of Launaea sarmentosa and Aegialitis rotundifolia roxb.

Results

The AELS and AEAR extract presented a significant (***p < 0.001) dose dependent increase in reaction time in writhing method and showed inhibition of 63.1% and 57.1% respectively at the doses of 400 mg/kg body weight while standard drug showed (P < 0.001) inhibition of 69.23%. In tail immersion method, AELS and AEAR showed maximum time of tail retention at 30 min in hot water i.e. 6.93 sec and 6.54 sec respectively at highest doses of 400 mg/kg body weight than lower dose while standard pentazocine showed reaction time of 7.62 sec. The AELS and AEAR extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant inhibition of paw volume by 32.48% and 26.75% respectively at the dose of 400 mg/kg body weight while the value at the dose of 200 mg/kg body weight were linear to higher dose at the 3^rd hour of study. On the other hand, Standard indomethacin inhibited 40.13% of inflammation (***P < 0.001). In Cotton-pellet granuloma method, AELS and AEAR extract at the dose of 400 mg/kg body weight exhibited inhibition of inflammation of 34.7% and 29.1% respectively while standard drug showed (P < 0.001) inhibition of 63.22%. Intraperitoneal administration of AELS and AEAR showed dose dependent decrease in body temperature in brewer’s yeast induced hyperthermia in rats at both doses. However, AELS significantly decreased body temperature (***p < 0.001) at 400 mg/kg compared to control.

Conclusions

Present work propose that the methanolic extract of Launaea sarmentosa and Aegialitis rotundifolia roxb possesses dose dependent pharmacological action which supports its therapeutic use in folk medicine possibly mediated through the inhibition or blocking of release of prostaglandin and/or actions of vasoactive substances such as histamine, serotonin and kinins.     

Antileishmanial effect of cisplatin against murine visceral leishmaniasis

Drug development in visceral leishmaniasis is extremely vital as the existing therapeutic modalities are plagued by the unwanted twosome of toxicity and drug resistance. Antineoplastic drugs have in the past been effective against the parasitic infections, for example, miltefosine. Cisplatin is a first-generation platinum-containing drug, used in the treatment of various solid tumors. Its in vitro antileishmanial effect has already been demonstrated. In the present study, the leishmanicidal potential of two doses (0.5 mg/kg body weight and 1 mg/kg body weight) of the drug was studied in BALB/c mice. The antileishmanial effect of the drug was revealed by significant reduction in the parasite burden. The infected and treated animals were also found to exhibit increased DTH responses. An initial transient and reversible increase in levels of SGOT, SGPT, BUN, blood urea, creatinine and phosphorus was observed in infected animals treated with both doses of the drug. The reduction in parasite load, increase in DTH response and various biochemical parameters were more pronounced in animals treated with 1 mg/kg body weight of cisplatin as compared to those treated with 0.5 mg/kg body weight of the drug. Though some histopathological changes were observed in the kidneys of animals treated with 1 mg/kg body weight of cisplatin, no such change was observed in mice treated with the lower dose. Thus, we have for the first time characterized the in vivo effect of cisplatin in murine experimental visceral leishmaniasis.     

Biodistribution of bis[β-(N,N,N-trimethylamino)ethyl]selenide-75Se diiodide,a potential articular cartilage imaging agent

In an effort to develop a specific radiodiagnostic agent for articular cartilage imaging, we have investigated the biodistribution of bis[β-(N,N,N-trimethylamino)ethyl]selenide-⁷⁵Se diiodide (⁷⁵Se BISTAES) in rabbits. At an intravenous dose of 5 mg/kg, the greatest localization of the compound occurred in articular cartilage 15 min after injection. The compound was excreted rapidly in the urine. The results suggest that ⁷⁵Se BISTAES has potential clinical use as an articular cartilage imaging agent.