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The investigation of “Inert Minerals and Botanicals Synergism with Spinosad: co-toxicity against Callosobruchus maculatus in Stored Blackgram” was performed in the Laboratory of the Department of Entomology, Agricultural College, Bapatla, during 2020-21. The inert minerals and botanicals were mixed with Spinosad and used for the bioassay. The data were recorded at 24, 48 and 72 hours after the release of the test insect, and probit analysis was performed to calculate the LD50. By using the LD50 of inert minerals and botanicals alone and in combination with spinosad, the co-toxicity coefficient was calculated. Among all the treatments, the highest co-toxicity coefficient (433.33) was recorded for diatomaceous earth, indicating increased efficacy and synergism between diatomaceous earth and Spinosad.

Being a pulse crop, green gram has huge scope in crop improvement in terms of productivity and other yield related parameters. Genetic variability is a preferable option for breeders in breeding programme for varietal development programme and others crop improvement aspect. The present investigation was framed to create the variability in mung bean var. GAM 8 during the seedling period through gamma (γ) irradiation. The significant variation was observed in germination percentage and it was found that dose dependent relationship between the germination rate and dose. Significantly minimum germination percentage (22.38 %) was observed in 700 Gy but optimal lethal dose (LD50) calculated through Probit analysis based on germination percentage was revealed at 540.26 Gy. Data revealed that γ irradiation had significantly reduced the seedling growth parameters such as shoot length (10.05 cm), shoot dry weight (19.68 mg), seedling length (13.90 cm), vigour index I (311.01) and II (509.01) was registered in 700 Gy while minimum root length (3.83 cm) was occurred in 600 Gy γ irradiation. Growth reduction (GR) 50 and 30 with respect to the seedling length was occurred respectively at 1093.79 and 1469.74 Gy. Therefore, this finding as the source of genetic variability would be used in future breeding and crop improvement programme like enhancement of yield potentiality and stress management in mung bean var. GAM 8.

Background: Kashmir Himalaya hosts the most diverse and rich flora in the world, which serves as grazing land for millions of small ruminants in the area. While most plant species are beneficial, some can be poisonous, causing economic losses and animal health issues for livestock. Consequently, this study is the first comprehensive report on the traditional phyto-toxicological knowledge in District Muzaffarabad and the assessment of its authenticity through experimental studies in rats.Methods: The data regarding traditional knowledge was gathered from 70 key respondents through semi-structured interviews, which was quantitatively analyzed and authenticated through plant extract testing on Wistar female rats and comparison with published resources.Results: A total of 46 poisonous plant species belonging to 23 families and 38 genera were reported to be poisonous in the study area. Results revealed that leaves were the most toxic plant parts (24 species, 52.1%), followed by the whole plant (18 species, 39.1%), stem (17 species, 36.9%), and seeds (10 species, 21.7%). At the organ level, liver as most susceptible affected by 13 species (28.2%), followed by the gastrointestinal tract (15 species, 32.6%), nervous system (13 species, 8.2%), dermis (8 species, 17.3%), renal (7 species, 15.2%), respiratory (4 species, 8.7%), cardiovascular system (3 species, 6.5%), and reproductive system (2 species, 4.3%). The poisonous plant species with high Relative frequency citation (RFC) and fidelity level (FL) were Nerium oleander (RFC, 0.6; FL, 100), Lantana camara (RFC, 0.6; FL, 100), and Ricinus communis (RFC, 0.6; FL, 100). Experimental assessment of acute toxicity assay in rats revealed that Nerium oleander was the most toxic plant with LD50 of (4,000 mg/kg), trailed by Ricinus communis (4,200 mg/kg), L. camara (4,500 mg/kg), and Datura stramonium (4,700 mg/kg); however, other plants showed moderate to mild toxicity. The major clinical observations were anorexia, piloerection, dyspnea, salivation, tachypnea, constipation, diarrhea, tremor, itchiness, and dullness.Conclusion: This study showed that numerous poisonous plants pose a significant risk to the livestock industry within Himalayan territory, leading to substantial economic losses. Consequently, it is of utmost importance to conduct further comprehensive studies on the phytotoxicity of plants.

Ruta montana L. is an annual aromatic plant of the family rutaceae. Quantitative analysis of the methanolic crude extract of Ruta montana L. yielded 8.43%, whereas the qualitative analysis revealed the presence of alkaloid or coumarin. The Litchfield and Wilcoxon method calculated the LD50 of the crude methanolic extract of Ruta montana L. in Wistar albino female rats at 393.18 mg/kg. This allows the plant to be classified as moderately toxic. The subacute toxicity study of the methanolic crude extract of Ruta montana L. in female Wistar albino rats treated with 100 mg/kg (≈ 1/4 LD50) and intraperitoneally showed a significant increase in body weight of the rats treated at the 4th week. Animals treated and sacrificed after 30 days showed a disturbance of the relative mass of the organs. Biochemical parameters of hepatic function assessment showed a significant increase in PAL with elevation of AST and ALT, whereas those of renal function revealed a significant decrease in creatinine with an increase in urea. Hematologic parameters recorded a decrease in RBC, HGB and HCT. The histological sections of the treated rats reveal the existence of blood congestion in the central veins and liver tissues, foci of necrosis and steatosis in the liver, blood congestion and some glomerular atrophy in the kidneys, as well as blood congestions and developed follicles without oocytes in the ovaries.

Fentanyl overdose is a survivable condition that commonly resolves without chronic overt changes in phenotype. While the acute physiological effects of fentanyl overdose, such as opioid-induced respiratory depression (OIRD) and Wooden Chest Syndrome, represent immediate risks of lethality, little is known about longer-term systemic or organ-level impacts for survivors. In this study, we investigated the effects of a single, bolus fentanyl overdose on components of the cardiopulmonary system up to one week post. SKH1 mice were administered subcutaneous fentanyl at the highest non-lethal dose (62 mg/kg), LD10 (110 mg/kg), or LD50 (135 mg/kg), before euthanasia at 40 min, 6 h, 24 h, or 7 d post-exposure. The cerebral cortex, heart, lungs, and plasma were assayed using an immune monitoring 48-plex panel. The results showed significantly dysregulated cytokine, chemokine, and growth factor concentrations compared to time-matched controls, principally in hearts, then lungs and plasma to a lesser extent, for the length of the study, with the cortex largely unaffected. Major significant analytes contributing to variance included eotaxin-1, IL-33, and betacellulin, which were generally downregulated across time. The results of this study suggest that cardiopulmonary toxicity may persist from a single fentanyl overdose and have wide implications for the endurance of the expanding population of survivors.

Annual ryegrass (Lolium rigidum Gaudin) is a problematic weed in most of the cropping regions in Australia. Evolved herbicide resistance to multiple modes of action groups, the lack of new herbicidal molecules, and the emergence of late cohorts in winter season crops necessitate the use of existing herbicides in an innovative way to control L. rigidum. Pendimethalin as pre-emergence (PRE) is used for L. rigidum control; however, it is unable to control late cohorts of L. rigidum in winter season crops. Pot studies were conducted from 2019 to 2021 to evaluate the effect of a post-emergence (POST) application of pendimethalin with six doses (0, 220, 440, 880, 1,760, and 3,520 g a.i. ha-1) on L. rigidum control in addition to crop safety in wheat, barley, and sorghum. POST application of pendimethalin was found to be safe for wheat and barley, and the biomass reduction in both crops at varied rates (220 to 3,520 g ha−1) of pendimethalin ranged from 10% to 20%. A dose–response study revealed that the pendimethalin dose required for 50% mortality and growth reduction of L. rigidum was 179 and 144 g ai ha−1, respectively. Pendimethalin at 880 g ai ha−1 completely killed late cohorts of L. rigidum. These results suggest that the POST application of pendimethalin can be used for the effective control of late cohorts of L. rigidum in wheat and barley crops. POST application of pendimethalin suppressed the biomass of sorghum plants compared with the non-treated control treatment, and biomass reduction in sorghum at different pendimethalin doses ranged from 32% to 40%. Results implied that POST applications of pendimethalin in wheat and barley can diversify herbicide programs in managing L. rigidum and may help in delaying the evolution of resistance in this weed.

Abstract Consumption of wild mushrooms has increased in recent years; however, not all of them are edible and there is no precise information on those that may cause poisoning. Therefore, studies to obtain data about their toxicity are needed. For this purpose, we used the brine shrimp Artemia franciscana, a crustacean employed in toxicity tests and with wide application in the toxin detection, including mycotoxins. Mushrooms were collected in the state of Jalisco, Mexico, with which aqueous extracts were prepared. Dilutions of the stock solution of each extract were made to final concentrations of 50, 100, 250, 500, and 1000 µg/mL. Potassium dichromate (PD) was used as positive control and artificial seawater as negative control. The median lethal dose (LD50) of extracts on nauplii of A. franciscana was calculated. The aqueous extracts obtained from Amanita amerivirosa, A. muscaria, Chlorophyllum molybdites, and Leucopaxillus amarus showed a LD50 < 70 µg/mL, similar to PD (LD50 = 37 µg/mL). This is the first indication of the probable toxicity of Leucopaxillus amarus in humans. Cantharellus cibarius and Scleroderma texense caused the lower toxicity to the nauplii. The brine shrimp bioassay was effective in evaluating the toxicity of Basidiomycota. Scleroderma texense has been reported to be toxic, but it was not for this crustacean nauplii, and probably not to humans either, as recent literature has reported.

Four hundred tubers of four genotypes, two brown and two black tiger nuts were subjected to Ethyl Methanesulfonate (EMS) and Colchicine treatments at concentrations of 0 %, 0.1 %, 0.25 %, 0.5 % and 1.0 % for 24 h. Each genotype had twenty tubers treated with each of the five different concentrations and were planted using Complete Randomized Design (CRD) in a greenhouse. Quantitative data was collected and LD50 and RD50 were analysed using Excell 2016 and Genstat 11.2. A general decreasing trend in percentage germination and plant height was observed with increasing concentrations of mutagens applied. An EMS treatment had LD50 and RD50 values of 0.97 % and 1.49 % for black and 0.63 % and 1.63 % for brown genotypes.Similarly, the percentage colchicine treatment had LD50 and RD50 values of 1.65 % and 19.51 % concentrations for black and 0.91 % and 1.71 % concentrations for brown genotypes.

Gardenia, as a medicinal and edible herb, has the pharmacological activity of protecting the liver and cholagogue, but the hepatotoxicity induced by the chemical component genipin (GP) limits its application. The aim of this study was to evaluate the acute and subacute hepatotoxicity of genipin in normal mice and mice with α-naphthalene isothiocyanate (ANIT)-induced liver injury. The results of the acute study showed that the LD50 of genipin was 510 mg/kg. Genipin exhibited hepatotoxicity in normal and jaundiced mice at doses of 125 mg/kg, 250 mg/kg, and 500 mg/kg, which increased with dose. In a 28-day subacute study, the 50 mg/kg and 100 mg/kg dose groups showed some pharmacodynamic effects at 7 days but exhibited hepatotoxicity that increased with time and improved after drug withdrawal. In addition, based on proteomics, the mechanism of liver injury induced by genipin may be related to the disruption of the UDP-glucuronosyltransferase system and cytochrome P450 enzyme activity. In conclusion, this study showed that genipin hepatotoxicity was time- and dose dependent, but it is worth mentioning that hepatotoxicity was reversible. It is hoped that this study will provide a scientific basis for circumventing the adverse effects of genipin.

ABSTRACT: Deoxynivalenol (DON) has a strong toxic effect on the gastrointestinal mucosa of poultry. In this study, we evaluated chicken embryo development and glandular stomach damage to clarify the immunotoxic effects of DON injected through the allantoic cavity of chicken embryos. The glandular stomach index, routine blood indices, plasma inflammatory factors, pathological changes in the glandular stomach, and transcriptome results were analyzed in the hatching chicks. The results showed that DON was supertoxic to chicken embryos, causing edema, shedding, and bleeding of the mucosa of the glandular stomach, which triggered inflammatory reactions. As the toxin concentration increased, the immune system was successively activated and inhibited, and regulation was carried out by the differential regulation of the mitogen-activated protein kinase (MAPK) signal pathway. These results suggested that the immunotoxic effect of DON on the glandular stomach of chicken embryos was closely related to the regulation of the MAPK signaling pathway.

The Western honeybee (Apis mellifera) plays a crucial role in pollinating natural ecosystems and crops. They support global food production, maintenance of biodiversity, and generation of income from hive by-products. In modern agriculture, frequent use of chemicals, such as herbicides, exposes bees directly to their toxicity. Whereas the noxious effects of commonly used herbicides on honeybees have become an emerging concern worldwide, their toxicity on the African subspecies Apis mellifera scutellata Lepeletier is unknown. In this study, we exposed A. m. scutellata to field concentrations of both paraquat and glyphosate and determined their effects on bee food consumption and survival rates. We found that the mortality rates of bees upon herbicide ingestion were concentration dependent. Lethal doses of paraquat and glyphosate were 10.8 and 229.5 µg/bee, respectively. Our findings suggest that the African honeybee is susceptible to paraquat and tolerant to glyphosate than its European counterpart. This study provides a baseline to help in regulating herbicide use and/or establishing their safe concentrations to protect biodiversity, particularly the beneficial pollinator insects such as bees. [ABSTRACT FROM AUTHOR]

Formononetin is a phytoestrogen which possess different pharmacological activities. The intraperitoneal route permits the identification of target organs involved in toxicity without compromising the molecule's bioavailability. The current study investigated the safety profile of intraperitoneal formononetin in Swiss albino mice. For acute toxicity study, formononetin administered intraperitoneally to mice at the doses of 5, 50, 100, 150, 200, and 300 mg/kg for 14 days. For the subacute toxicity study, mice were intraperitoneally administered with formononetin (12.5, 25, and 50 mg/kg) daily for 28 days. During the acute study, no deteriorating effect was observed on body weight, food and water intake, no behavioral changes were observed in animals. The lethal dose 50% (LD50) of formononetin was determined to be 103.6 mg/kg of BW, with a no observed adverse effect level (NOAEL) of 50 mg/kg of BW. Mortality was observed in the 300 mg/kg dose group and histopathological changes such as a mild degree of diffuse granular degeneration in the liver but for rest all doses did not have any adverse effect. In subacute study, no signs of adverse effects, mortality, no changes in body weight, food and water intake, and hematological and biochemical parameters were observed. Histopathology of subacute study indicates, formononetin did not have any noxious effect on organs. Formononetin shows mortality at acute dose 300 mg/kg and LD50 at 103.6 mg/kg of BW, with a NOAEL of 50 mg/kg of BW, rest all doses for acute and sub-acute are safe when given intraperitoneally. [ABSTRACT FROM AUTHOR]

Air dried seeds were exposed to continuous and fractionated doses of gamma radiation at dosage levels of 10KR, 20KR, 40KR, and 80KR in an experiment to measure germination and early seedling growth pattern change in Bauhinia purpurea. Seeds were pre-soaked for 24 hours at room temperature (27.5%-1.700°C) after treatment. Seeds were scarred for proper imbibition prior to pre-soaking. A petri plate with Whatman filter paper no. 1 and different dosages of seeds was used. Lab temperatures ranged from 240°C to 340°C. There were 50 seeds in each set, each with four replications. Results from the irradiation and control treatments showed a discernible difference. With the exception of the cotyledons growth dimension, almost all dose level treatments decreased the measured parameters when compared to untreated sets (control). Following continuous and fractionated treatments at dose levels of 10, 20, and 80 KR, the Control set showed the highest levels of GP, GV, and GEI. In comparison to lower dose levels (10&20KR), the higher doses (40 & 80KR) were more effective at lowering the germination value. For various doses, Bauhinia purpurea's hypocotyl was more radio resistant than its roots. The leaves and the shoot displayed greater radio sensitivity. Under an 80KR dosage level, there were no shoots or leaves. Gamma radiation fractioned dosages were more successful at preventing Bauhinia purpurea seedling germination and growth. LD-50 readings varied depending on the parameters that were examined. [ABSTRACT FROM AUTHOR]

The aim: to study the pathogenicity of non-pigmented P. aeruginosa isolates compared to those that synthesize pigment during long-term storage for broiler chickens. Materials and methods. Bacteriological studies were carried out in accordance with generally accepted methods. Initially, P. aeruginosa and other bacterial microflora were isolated from poultry farms, pathological material from poultry. The type of microorganisms was identified using Bergey's identifier. The obtained isolates were examined by morphological characteristics (according to Gram), tincture, cultural, biochemical, pathogenic properties and sensitivity of selected cultures to antibiotics were studied. After the expiration of 3 years, the main biological properties of the isolates were monitored. To establish pathogenic properties, a bioassay was performed on white mice and one-week-old broiler chickens of the Cobb 500 cross (intraperitoneally by washout from daily agar culture at a dose of 0.2 cm³, which corresponds to the previously established LD50). The results. With parenteral infection by washout from agar daily culture of pigmentless isolates at a dose of LD50, chickens died within the first - second day, in this case 87.50 % of the cultures showed pathogenicity. Experimental parenteral infection with washings from a daily culture of pigmented isolates of P. aeruginosa at a dose of LD50 led to the death of one-week-old chickens within 24-48 hours, in this case 75.00 % of the isolates showed pathogenicity. Clinical and pathological signs of infection with pigmented and non-pigmented P. aeruginosa isolates were similar. Conclusions. A comparative analysis of cases of pathogenicity of non-pigmented and pigmented isolates of P. aeruginosa on one-week-old broiler chickens of the Cobb-500 cross was carried out. In the experiment, we found that among the non-pigmented isolates, compared to the pigmented pathogenic isolates, 12.5 % more were detected in chickens. This emphasizes the importance of differential diagnosis for pseudomonosis, because infection with non-pigmented strains often goes undiagnosed [ABSTRACT FROM AUTHOR]

In our study we investigated the acute toxicity of а newly synthesized creatine lysinate as well as its effect on the biochemical parameters in mice. Creatine lysinate exerts better solubility in water (3.3%) in comparison to creatine monohydrate (1.4%) at 20 °C and it is determined as a non-toxic after intraperitoneal (LD50 – 4543 mg/kg) and oral administration (LD50 > 8000 mg/kg). Oral administration of creatine lysinate at doses of 3 g/kg/day and 6 g/kg/day for 2 weeks reduced the creatine kinase levels, which indicates muscle protection. An increased levels of liver enzymes like alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) was observed after the supplementation with creatine lysinate at both administered doses and the level of lactate was comparable both in the studied and the control group. [ABSTRACT FROM AUTHOR]

Diseases have been part of man existence since time immemorial. The present scenario for controlling these diseases is aimed at application of target, cost-effective and biodegradable phytochemical products. Therefore, in the present study the larvicidal activities of Gliricidia sepium, Azadirachta indica and Hyptis suaveolens leaf extracts against anopheles mosquito was studied. Qualitative phytochemical screening was carried out while standard scientific protocols with minor modifications were adopted for the larvicidal bioassay. The results show that the plants contain all the phytochemicals screened with tannins, flavonoid and saponin being the most abundant. Also, A. indica exhibited the highest larvicida activity of 65% followed by G. sepium (60 %) and the control (water) was found to have lowest larval mortality percentage of 0% after 24 hrs. The calculated LD50 were 0.48 mg/ml, 0.65 mg/ml and 3.18 mg/ml for G. sepium, A. indica and H. suaveolens respectively. These suggest that G. sepium and A. indica may be exploited for the production of antibiotics and biolarvicides. However, further investigations are needed to identify the active ingredient (s) of the extract responsible for the observed bioactivity in this study. [ABSTRACT FROM AUTHOR]

Background: Mutation breeding is one of the cheapest and surest method of plant breeding. In mutation breeding program effectiveness and efficiency of mutagens could be helpful to realize the spectrum of desirable mutations in the treated populations. The effectiveness and efficiency of two mutagens EMS and gamma rays were studied in two varieties of cowpea [Vigna unguiculata (L.)Walp.]. Methods: In the present investigation, the seeds of two varieties of cowpea, phulepandhari and VCM-8 were treated with gamma rays and EMS to obtain the spectrum and frequency of chlorophyll mutations in M2 generation. Mutagenic effectiveness and efficiency were calculated using frequency of chlorophyll mutations. Result: The individual treatment of EMS was found to be more efficient than gamma rays to induce chlorophyll mutants. A progressive increase in mutation frequency of chlorophyll mutations was observed with increasing doses. Four different types of chlorophyll mutants, such as, chlorina albina, xantha and viridis were induced with effect of mutagens. The highest frequency of chlorophyll mutations was reported in the gamma rays. There was a dose dependent increase in the spectrum and frequency of chlorophyll mutations. The lower dosages of gamma rays and EMS were proved to be most effective and efficient. Among two mutagens used EMS was much more effective than gamma rays in both the varieties viz. variety phulepandhari and VCM-8. [ABSTRACT FROM AUTHOR]

Organotin compounds are organometallic compounds composed of one or more tin-carbon (Sn-C) bonds. Organotin compounds have been shown to have anticancer, antibacterial, and antitumor activities. Based on the several activities of the organotin group, it is hoped that the Dibutyltin (IV) Bis-N-Benzylmethyl Dithiocarbamate compound has the potential to be developed as a new drug candidate. To be a candidate for a new drug, the study was aimed to test and determine the safety level of the compound. Study to determine the LD50 value and category of toxicity of the Dibutyltin (IV) Bis-N-Benzylmethyl Dithiocarbamate compound in white mice (Mus musculus). This research is a laboratory experimental study using 40 white mice, consisting of 20 male mice and 20 female mice. The dose of the test substance was 240, 480, and 960mg/Kg body weight. Observations of mice were carried out for 24 hours by observing the number of dead animals and seeing toxic symptoms, body weight, and ROW (Relative Organ Weight) then the data were analyzed statistically. The results showed that the dose of 960 mg caused the most death with LD50 values of 776.2mg and 794.3mg of toxic symptoms, weight loss in mice, and an effect on ROW. This compound can cause death in male and female mice, with the LD50 value of male mice being 776.2mg/kg body weight and female mice at 794.3mg/ kg body weight, and this compound is categorized as slightly toxic.

Enrofloxacin is a broad-spectrum synthetic antimicrobial drug widely used in veterinary medicine. The present study aimed to determine the effective enrofloxacin dose for treating Pseudomonas aeruginosa and Enterococcus faecalis infection in Oreochromis niloticus. P. aeruginosa and E. faecalis isolates were verified using selective differential media and biochemically using the Vitek 2 test. Bacterial isolates were virulent for O. niloticus with LD50 equal to 2.03 × 106 and 2.22 × 107 CFU fish−1 for P. aeruginosa and E. faecalis, respectively. Infected fish suffered from decreased feed intake followed by off-food, tail erosion, darkening of the external body surface, exophthalmia, ascites, and loss of escape reflex. Internally, congested hemorrhagic hepatopancreas with engorged distended gall bladder were dominant. The posterior kidney was congested with enlarged spleen, and empty elementary tract. Pathologically, severe degenerative changes were dominant in the hepatopancreas, posterior kidney, spleen, stomach, and gills of infected fish. Antimicrobial sensitivity test indicated the high susceptibility of P. aeruginosa and E. faecalis to enrofloxacin with MIC estimated at 1 and 0.0625 µg/mL, respectively. Enrofloxacin effectively protected O. niloticus against E. faecalis and P. aeruginosa infection when used with medicated feed at doses of 10 and 20 mg kg−1 body weight.

Mosquitofish, Gambusia affinis, are eponymous larval mosquito predators. Their ability to colonize and survive in habitats that are uninhabitable by other potential predators allows them to naturally manage larval mosquito populations in most ground pools they are present in. However, effluent from residential onsite wastewater treatment systems (OWTSs) appears to limit the presence of fish predators. This is especially problematic in Louisiana, where regulations allow the discharge of OWTS effluent into open drainage conveyances. To determine the effect of effluent on the capacity of mosquitofish for biocontrol in contaminated areas, we assessed the body condition metrics of populations from two effluent-exposed sites and two sites not exposed to effluent, determined the lethal effect of effluent-contaminated drainage water on fish, and measured the prey consumption rates in the presence of effluent. Female fish collected from effluent-impacted sites had a reduced somatic body condition and most females examined displayed masculinized anal fins resembling the male gonopodium structure. This trait was not seen in fish collected from the control sites and has not yet been documented in association with OWTSs or in the state of Louisiana. Fish from the control sites survived at effluent-contaminated water levels < 70%, and the prey clearance rates increased with dilution. Onsite wastewater treatment system effluent has significant effects on both the short- and long-term persistence of mosquitofish, their body composition, reproductive health, and larval mosquito consumption. These effects likely release mosquito larvae from suppression and may increase the threat of mosquito-transmitted pathogens in effluent-contaminated locations.

Zika virus (ZIKV) is a positive-sense single-stranded virus member of the Flaviviridae family. Among other arboviruses, ZIKV can cause neurological disorders such as Guillain Barré syndrome, and it can have congenital neurological manifestations and affect fertility. ZIKV nonstructural protein 5 (NS5) is essential for viral replication and limiting host immune detection. Herein, we performed virtual screening to identify novel small-molecule inhibitors of the ZIKV NS5 methyltransferase (MTase) domain. Compounds were tested against the MTases of both ZIKV and DENV, demonstrating good inhibitory activities against ZIKV MTase. Extensive molecular dynamic studies conducted on the series led us to identify other derivatives with improved activity against the MTase and limiting ZIKV infection with an increased selectivity index. Preliminary pharmacokinetic parameters have been determined, revealing excellent stability over time. Preliminary in vivo toxicity studies demonstrated that the hit compound 17 is well tolerated after acute administration. Our results provide the basis for further optimization studies on novel non-nucleoside MTase inhibitors.

Growing numbers of disease outbreaks and a wider variety of pathogens have emerged as a result of aquaculture's expansion, intensification, and commercialization. In the current work, we isolated and identified a new multi-drug resistant pathogenic bacteria, Acinetobacter pittii strain COF_AHE14, that causes mass death in rohu (Labeo rohita) during a post-monsoon disease outbreak in the aquaculture farm of Tripura, India. The isolate was initially identified based on morphological and biochemical information, and the species was validated through molecular characterization of the 16S rRNA gene sequence and phylogenetic analysis. An experimental infectivity study in healthy rohu (Labeo rohita), haemato-biochemical and immune-pathophysiological analysis, histopathological study, and fulfilment of the Koch’s postulate all confirmed the pathogenicity of the isolated bacteria. The LD50 of A. pittii strain COF_AHE14 in an experimental infection was 4.1 × 106 CFU fish-1, and the clinical signs observed, such as ulcerative lesions and haemorrhages on the skin and tail and fin rot, were similar to those of the farm-diseased fish. Total RBC count, Hb, PCV, MCV, glucose, Na+, albumin, respiratory burst and anti-protease activity were significantly (p

Background: This study was designed to quantify the composition of the ethanolic extract of Artemisia absinthium through gas chromatography-mass spectrometry analysis and ensure in vivo safety of A. absinthium extract-loaded polymeric nanoparticles (ANPs) before considering their application as a drug carrier via the oral route. Methods: We synthesized N-isopropylacrylamide, N-vinyl pyrrolidone, and acrylic acid crosslinked polymeric NPs by free-radical polymerization reaction and characterized them by Fourier-transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering spectroscopy. Different concentrations of extract (50 mg/kg, 300 mg/kg, and 2,000 mg/kg body weight) were encapsulated into the hydrophobic core of polymeric micelles for the assessment of acute oral toxicity and their LD50 cut-off value as per the test procedure of OECD guideline 423. Orally administered female Wistar rats were observed for general appearance, behavioral changes, and mortality for the first 30 min, 4 h, 24 h, and then, daily once for 14 days. Result: ANPs at the dose of 300 mg/kg body weight were used as an initial dose, and rats showed few short-lived signs of toxicity, with few histological alterations in the kidney and intestine. Based on these observations, the next set of rats were treated at a lower dose of 50 mg/kg and a higher dose of 2,000 mg/kg ANPs. Rats administered with 50 mg/kg ANPs remained normal throughout the study with insignificant histological disintegration; however, rats treated at 2,000 mg/kg ANPs showed some signs of toxicity followed by mortality among all three rats within 24-36 h, affecting the intestine, liver, and kidney. There were no significant differences in hematological and biochemical parameters among rats treated at 50 mg/kg and 300 mg/kg ANPs. Conclusion: We conclude that the LD50 cut-off value of these ANPs will be 500 mg/kg extract loaded in polymeric NPs. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate endosulfan effects on the Acetylcholinesterase (AChE) enzyme and gene in albino mice. Thirty selected male albino mice were randomly divided into 3 groups. The first group was control group (G1), while the other two treated groups were injected intraperitoneally twice per week with two doses of endosulfanG2 (3 mg/kg) and G3 (17 mg/kg) for 21 and 45 days respectively. The results recorded a significant decrease in AChE enzyme in the group treated with 17 mg/kg b.wt. (3986.67 ±170.32 U/L),compared to the control (5584.33 ±140.35 U/L)and treatment group with 3 mg/kg b.wt.(5556.00 ±341.01) U/L for 21 days. Also, there was a significant decrease in the enzyme level between the two treated groups (4688.00 ±221.49 U/L)and (3413.67 ±305.42 U/L) for the duration of 45 days of the dose, compared with the control group (5584.33 ±140.35 U/L), and increased expression of AChE gene in the treated groups. Gene expression fold in all treated groups was higher than in the control group with the highest recorded value of 14.320at 17 mg/kg for 45 days, compared with the control group. [ABSTRACT FROM AUTHOR]

Terminalia arjuna (T.arjuna) bark is extensively used by Indian herbal medicine practitioners for treating various cardiovascular ailments. Though multiple clinical trials and non-clinical studies have been reported on T.arjuna bark, the toxicology data was found to be inadequate. Hence, studies were conducted to establish the toxicology profile of T.arjuna bark. In the acute toxicity study, animals were administered with a single dose of 2000 mg/kg of T. arjuna bark hydroalcoholic extract, whereas in repeated dose toxicity study animals were administered with the extract at doses of 0, 100, 500, and 1000 mg/kg, once daily, for 28 consecutive days, and on day 29, all the animals were humanely sacrificed after the collection of required blood samples. There were no mortality or clinical signs of toxicity observed after administration of a single dose of 2000 mg/kg of T. arjuna bark hydro-alcoholic extract. In the repeated dose toxicity study, there were no treatment-related adverse effects in any of the dose groups and control group animals in respect to clinical signs, body weight, feed consumption, haematology, clinical chemistry, urinalysis, and histopathology. Based on the results, LD50 of T. arjuna bark hydro-alcoholic extract is concluded as >2000 mg/kg. No-Observed-Adverse-effect Level of T. arjuna bark hydroalcoholic extract from 28-day repeated dose toxicity study is established at 1000 mg/kg/day. [ABSTRACT FROM AUTHOR]

The acute anti-inflammatory activity of onion peel-derived gold nano-bioconjugate was already established earlier. The current study was aimed to investigate the acute oral toxicity of onion peel-derived gold nano-bioconjugate (GNBC) for safe therapeutic utilization in vivo. The acute toxicity study was carried out in female mice for 15 days and showed no mortality and any abnormal complications. The lethal dose (LD50) was evaluated and found to be higher than 2000 mg/kg. After 15 days, animals were euthanized and hematological, and biochemical analyses were performed. In all hematological and biochemical assays, treated animals did not show significant toxicity when compared to the control group. The body weight, behavior, and histopathological studies showed that GNBC is nontoxic. Thereby, the results suggest that onion peel-derived gold nano-bioconjugate GNBC can be utilized for therapeutic applications in vivo. [ABSTRACT FROM AUTHOR]

Development of "indirect antioxidants" capable of activating redox-sensitive signaling systems, primarily the Keap1/Nrf2/ARE system, is a promising area of modern pharmacology. Among its chemical inducers is the hydrophilic monosubstituted monophenol sodium 3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonate (TS-13) that we have developed. The aim of this study was to investigate the antiproliferative activity of TS-13 against BT-474 tumor cells in vitro and acute oral toxicity in mice in vivo. The relationship between TS-13 concentration and the proliferative activity of BT-474 human breast ductal carcinoma cells was determined by the MTT test with calculation of IC50. The results were compared with the previously obtained data for the MCF-7 line and compared with the functional properties of cells based on the level of gene expression (in silico GSEA analysis). Acute toxicity in vivo was examined on 50 C57Bl/6y female mice, which had a solution of TS-13 in distilled water administered to them at various doses via an intragastric tube. LD50 obtained experimentally was compared with predicted in silico using the GUSAR web service. The IC50 value of TS-13 for BT-474 cells calculated from the equation of exponential approximation was 59.5 μM, which was 2.2 times less than previously obtained for MCF-7 cells. This may be due to functional differences between BT-474 and MCF-7 cells, as evidenced by the results of GSEA analysis. The LD50 value established in the experiments in vivo was 936 mg/kg body weight of mice. The obtained value satisfactorily corresponds to the predicted in silico (561 mg/kg), although in reality the compound turned out to be somewhat less toxic than could be expected based on its structure. The study of the acute toxicity of the new water-soluble monophenol TS-13 allows it to be assigned to hazard class 4 on the Hodge–Sterner scale (low-toxicity compounds) or to hazard class 3 according to GOST (State Standard) 12.1.007-76 (moderately hazardous substances). [ABSTRACT FROM AUTHOR]

In order to increase genetic variability for the improvement of groundnut, two varieties, namely Kp29 and Fleur11, were treated with six different gamma irradiation doses. A significant effect of mutagenesis was distinctly observed in the stem lengths, roots, and survival percentage in both varieties. The radiosensitivity test showed a mean lethal dose of 436.51Gy for Kp29 and 501.18 Gy for Fleur11. Furthermore, this study revealed putative mutants with variable agromorphological traits. Seven chlorophyll mutants and various seed shape and color mutants were obtained. This study demonstrates the potency of gamma irradiation to induce high genetic variability that led to the emergence of certain mutations of economic importance. [ABSTRACT FROM AUTHOR]

The conundrum of Cannabis sativa's applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, Cannabis sativa L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified Cannabis sativa L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified Cannabis sativa L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain. [ABSTRACT FROM AUTHOR]

Pangasius catfish, Pangasius nasutus, is a promising candidate for aquaculture due to its high market value. However, the presence of pathogenic bacteria in Aeromonas hydrophila is a major concern in P. nasutus farming in this country. This study determines the pathogenicity of A. hydrophila in P. nasutus. A total of 80 P. nasutus juveniles were intraperitoneally injected with 0, 10³, 105, and 107 CFU mL-1 of A. hydrophila and monitored until 240 hr. The infected moribund fish's kidneys, livers, and spleens were collected for histopathological analysis. The LD50-240hr value was found at 0.8 × 104 CFU/ml of A. hydrophila. The percentage of mortality in 0, 10³, 105, and 107 CFU/ml infected groups were found to be at 0, 40, 60, and 90%, respectively. The infected fish showed congestion at the base of the fin, ascites, enlarged gall bladder, and swollen spleen. It is the earliest report on A. hydrophila's pathogenicity in high-value native fish, P. nasutus. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs) are important therapeutic agents. The in vivo median lethal dose (LD50) assay has been commonly used to measure the potency of BoNT commercial preparations. As an alternative, we developed cell-based assays for abobotulinumtoxinA in both powder (Dysport®, Azzalure®) and liquid (Alluzience®) formulations using the in vitro BoCell® system. The assays demonstrated linearity over 50–130% of the expected relative potency, with a correlation coefficient of 0.98. Mean recoveries of 90–108% of the stated potency were observed over this range. The coefficients of variation for powder and liquid formulations, respectively, were 3.6% and 4.0% for repeatability and 8.3% and 5.0% for intermediate precision. A statistically powered comparability assessment of the BoCell® and LD50 assays was performed. Equivalence was demonstrated between the assays for the liquid formulation at release and end of shelf life using a paired equivalence test with predefined equivalence margins. For the powder formulation, the assays were also shown to be equivalent for release samples and when determining loss of potency following thermal degradation. The BoCell® assay was approved for establishing the potency of abobotulinumtoxinA for both powder and liquid formulations in Europe and for the powder formulation only in the USA. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine the mutagenic effectiveness, efficiency and lethal dose of gamma rays in papaya varieties CO7, Arka Prabhath and Arka Surya. Papaya seeds were exposed to various doses of gamma rays (0Gy, 100Gy, 150Gy, 200Gy, 250Gy, 300Gy, 350Gy, 400Gy, 450Gy and 500Gy) and the mutagenic effectiveness and efficiency of gamma rays were assessed based on the chlorophyll mutation frequency and biological damage in M1 plant basis. There was a negative relationship between mutagenic effectiveness and efficiency with the doses of gamma irradiation. LD50 value was optimized in CO7, Arka Prabhath and Arka Surya as 354, 348 and 341Gy respectively. Generally, the germination, survival and growth rate of papaya decreased with an increase in gammairradiation doses. Lower doses of mutations created very few mutations and higher doses of gamma irradiation induced lethality and sterility of seedlings whereas, lethal dose 50 has proved to be more effective in inducing desirable mutations in papaya. Since identifying the mutagenic efficiency and effectiveness of the mutagen and optimization of lethal dose is the preliminary step in any mutagenic experiment, this study will offer a foundation for further gamma irradiation studies in papaya to develop desirable mutants.

Combination of bovine serum albumin with microemulsions as constituting ingredient biopolymer has long been regarded an innovative method to address the surface functionalization and stability issues in the targeted payload deliveries, thereupon producing effectively modified microemulsions, which are superior in loading capacity, transitional and shelf-stability, as well as site-directed/site-preferred delivery, has become a favored option. The current study aimed to develop an efficient, suitable and functional microemulsion system encapsulating sesame oil (SO) as a model payload towards developing an efficient delivery platform. UV-VIS, FT-IR, and FE-SEM were used to characterize, and analyze the developed carrier. Physicochemical properties assessments of the microemulsion by dynamic light scattering size distributions, zeta-potential, and electron micrographic analyses were performed. The mechanical properties for rheological behavior were also studied. The HFF-2 cell line and hemolysis assays were conducted to ascertain the cell viability, and in vitro biocompatibility. The in vivo toxicity was determined based on a predicted median lethal dose (LD50) model, wherein the liver enzymes' functions were also tested to assess and confirm the predicted toxicity. [ABSTRACT FROM AUTHOR]

Glyphosate resistance is a serious problem in weed control, especially in oil palm plantations. However, evaluation of suspected resistant weeds such as Eleusine indica L. Gaertn at the gene level is still scarce in Indonesia. Here, target-site resistance to glyphosate of the EPSPS gene was evaluated. The objective of this study was to identify glyphosate resistance caused by mutation points in goosegrass biotypes from oil palm plantation in Jonggol, West Java, Indonesia. Bio-assay analysis was carried out by planting goosegrassin pots. Glyphosate was applicated using eight-level, namely 0, 0.125x, 0.25x, 0.5x, x, 2x, 4x, and 8x, where x was the recommended dose (972 g ha-1) for three replications. Weed damage was evaluated from plant biomass and then regression analysis was performed to obtain the LD50 and resistance index. The E. indica from block V had a reduced sensitivity status with 2.343 value of resistance index, and those from Block II biotype had a sensitive status with 1.588 resistance index. Alignment of the EPSPS gene showed no mutation was observed at two target-points, indicating that increasing resistance of E. indica in the study site could be controlled by other factors. Nevertheless, E. indica of block V biotype had a resistance potential due to the highest LD50. It is necessary to evaluate further the possibility of mutation in other target-points of the EPSPS gene. [ABSTRACT FROM AUTHOR]

Weed resistance, indicated by increasing the level of herbicide for control, might arise due to the continuous use of similar herbicides in the long term without any herbicide rotation. The objective of this research was to evaluate the status of dominant weeds in a guava orchard to determine weed control strategies. The research was carried out from November 2020 to June 2021 at Agribusiness Technology Park IPB, Bogor. Vegetation analysis to define dominance was carried out at 4 blocks using the square method. In each block, five sampling points were randomly selected. Seeds of C. kyllingia were collected and planted as many as 25 seedlings in polybags. Glyphosate herbicide was applied onto C. kyllingia in 3 replications using 9 doses, i.e., 0 (D0), 60.75 (D1), 121.5 (D2), 243 (D3), 486 (D4), 972 (D5), 1944 (D6), 3888 (D7), and 7776 g ha-1 (D8). C. kyllingia mortality percentages were analyzed using linear regression to obtain LD50. The results showed that the dominant weed was C. kyllingia. Block 4 showed the highest significant LD50 value at 759.11 g ha-1 with a resistance index of 2.67 (reduced sensitivity). The presence of dominant C. kyllingia was identified only at block 4, indicating the dominance could correlate with increasing resistance of the particular weed. [ABSTRACT FROM AUTHOR]

There are different tests for testing the impact of chemicals on bees: the acute oral test, the acute contact test and the chronic oral test. For honey bees, OECD guidelines are avialable stating how these tests need to be conducted. The endpoint of the tests is an LD50-value expressed in ug/bee, where the chronic test usually has the most conservative result. In current practise, the results of these tests are interpreted independently and the most conservative result is chosen for further evaluation. Unfortunately, in this approach it is not known how the different exposure regimes influence the result and what the time dependency of the LD50 values is. Extrapolation and interpretation issues between exposure regimes and time can be solved by using a mechanistic approach where time is explicitly considered and effects are interpreted with time-independent parameters. The already developed and published GUTS modelling framework was used as a starting point and was adapted to take into account the physiology of the bees and the details of the different existing tests for bees. It showed that the different bee tests (acute oral, acute contact and chronic) could be interpreted within this framework with one set of parameters describing the toxicity of a compound for bees. The framework was then applied to other be species to compare sensitivity leading to new insights in bee sensitivity and bee testing. [ABSTRACT FROM AUTHOR]

Three experiments were conducted to assess the effect of different doses of gamma radiation on various seedling traits; determine the optimum doses of gamma radiation for different faba bean genotypes; find out the variation in optimum doses with respect to the different times of sowings after irradiation and methods of irradiation. Five faba bean genotypes viz., L-2013-060, L-2013-092, Anandnagar Local, Gazipur Local and Bangla Gangachar were used in these experiments. In Experiment I, seeds of five experimental genotypes were exposed to different doses (100 Gy 200 Gy, 300 Gy, 400 Gy, 500 Gy, 600 Gy, 700 Gy and 800 Gy) of gamma radiation and were sown immediately after irradiation. In Experiment II, seeds of Bangla Gangachar and L-2013-060 were exposed to varying doses (100–800 Gy) of gamma radiation and were sown at seven sowings starting from 0 h to 24 h at 4-h intervals after irradiation. In Experiment III, L-2013-092 genotypes was exposed to different doses (100 –800 Gy) of gamma radiation with two different methods of irradiation. In Experiment I, the lethal dose 50 (LD50) values have arrived at 140 Gy, 669 Gy, 575 Gy, 386 Gy and 158 Gy for L-2013-060, L-2013-092, Anandnagar Local, Gazipur Local and Bangla Gangachar, respectively. The growth reduction 50 (GR50) doses for different seedling traits ranged from 130 Gy to 320 Gy for L-2013-060, 250 Gy to 480 Gy for L-2013-092, 130 Gy to 370 Gy for Anandnagar Local, 200 Gy to 350 Gy for Gazipur Local and 250 Gy to 400 Gy for Bangla Gangachar. In Experiment II, the values for LD50 of the genotypes Bangla Gangachar and L-2013-060 were significantly singular for different time intervals of sowing. The values of GR50 for most of the seedling traits were found to increase with the delay in sowing after irradiation from 4 to 24 h when compared with the immediately sown seed lots. In Experiment III, LD50 for L-2013-092 was 337 Gy with Method 1 and 669 Gy with Method 2. In Method 1, most of the growth parameters attained GR50 doses lower than Method 2. The first method was found to increase the radiosensitivity of L-2013-092. Every experimental genotype used in these three experiments showed dose-dependent retardation of different seedling traits. These optimized doses may be employed to establish mutant populations for exploiting the novel traits of faba bean. The time of sowing after irradiation and method of irradiation was found to be essential for confirming optimum doses. [ABSTRACT FROM AUTHOR]

Objective: To estimate the median lethal dose (LD50) and mean reductive dose (GR50) due to gamma radiation in Arachis pintoi var. Amarillo seeds. Design/methodology/approach: Ten doses were used (100, 200, 300, 400, 500, 600, 700, 800, 900 and 1000 Gy) plus a control (without radiation). The experimental design was completely random with three replications and 50 seeds per repetition. Seed germination was evaluated 29 days after sowing (das) and plant survival, plant height, root length and leaf area at 60 das. The LD50 and GR50 for survival and plants height were estimated by linear regression. Results: There was a significant reduction of seed germination and plant survival from 300 and 200 Gy doses compared to the control (61.64 and 49.15% each); for the plants height the dose was of 100 Gy (35.22%). There were no differences in the root length and leaf area with 100 and 200 Gy regard to the control. The LD50 was estimated at 212.54 Gy and the GR50 at 162.16 Gy. Findings/conclusions: The gamma radiation doses to induce genetic variation in A. pintoi var. Amarillo seeds were between 162 and 212 Gy. [ABSTRACT FROM AUTHOR]

Determination of median lethal dose (LD50) is a vital tool adopted by the World Health Organization for pre-clinical assessment of products for use in the management of snakebite envenoming, a condition which is now included among the list of Neglected Tropical Diseases in 2017. The current trend in the determination of LD50 involves the use of laboratory animals, tens or even hundreds of animals are sacrificed to achieve this goal. This study aimed to find reliable alternatives to this sacrificing of laboratory animals for research purposes. This study investigated the comparative similarities or differences in results obtained from the use of laboratory animals and embryonated eggs in the determination of LD50 in snake venom research. The median lethal dose (LD50) was determined using female mice using the up and down method and Probit method as well as embryonated eggs. There was no statistical difference in the LD50 of the venom of Bitis arietans obtained by the up and down method and that of the conventional probit analysis (p≤0.05) (0.325 mg/kg [probit] and 0.351 mg/kg [up and down] respectively). There was also no statistical difference in the LD50 of the venom of Bitis arietans by the up and down method, conventional probit method, and by the use of embryonated eggs (p≤0.05) (0.325 mg/kg [probit], 0.351 mg/kg [up and down], and 0.392 mg/kg [embryonated eggs). The three methods used produced values of LD50 that were within the range reported on the Australian snake and venom database of 2007. The results suggest embryonated eggs can conveniently replace the use of laboratory animals in the determination of LD50 in snake venom research to ease the ethical challenges posed by excessive use of laboratory animals in snake venom research. [ABSTRACT FROM AUTHOR]

Protozoa, in both humans and animals, are one of the leading causes of disease. International programmes introduced in many countries have helped reduce the incidence of disease. However, it has recently become increasingly difficult to achieve the goals set for the coming years. One of the main reasons for this, as with other pathogenic organisms, such as bacteria and fungi, is the increasing resistance to current methods of treating and preventing infection. Therefore, new therapies with high efficacy are needed. In the present study, the novel mixtures of essential oils (EOs), clove, garlic, Ceylon cinnamon, and rosemary with organic acids (acetic, propionic, lactic) and metal ions (Cu, Mn, Zn) were tested against five selected model protozoa (Euglena gracilis, Gregarina blattarum, Amoeba proteus, Paramecium caudatum, Pentatrichomonas hominis). The cytotoxicity and potential anticancer activity of the obtained combinations were tested on the human fibroblasts (NHDF) and human cancer cell lines (A549, MCF7, LoVo, HT29). All of the mixtures showed very good antiprotozoal properties. The most efficient were the combination of clove and rosemary essential oils, mixtures of acids, and Mn ions. The LD50 values were in the range of 0.001–0.006% and the LD100 values were 0.002–0.008%. All of the tested mixtures did not show cytotoxicity against normal cells, but did show growth inhibition against cancer cell lines. The most cytotoxic against cancer cells were combinations with cinnamon essential oil. Nevertheless, the proposed combinations containing essential oils, organic acids, and metal ions have high antiprotozoal activity, with low toxicity to healthy human cells. [ABSTRACT FROM AUTHOR]