The antidepressant-like effect of inosine in the FST is associated with both adenosine A1 and A2A receptors

Inosine is an endogenous purine nucleoside, which is formed during the breakdown of adenosine. The adenosinergic system was already described as capable of modulating mood in preclinical models; we now explored the effects of inosine in two predictive models of depression: the forced swim test (FST) and tail suspension test (TST). Mice treated with inosine displayed higher anti-immobility in the FST (5 and 50 mg/kg, intraperitoneal route (i.p.)) and in the TST (1 and 10 mg/kg, i.p.) when compared to vehicle-treated groups. These antidepressant-like effects started 30 min and lasted for 2 h after intraperitoneal administration of inosine and were not accompanied by any changes in the ambulatory activity in the open-field test. Both adenosine A₁ and A_2A receptor antagonists prevented the antidepressant-like effect of inosine in the FST. In addition, the administration of an adenosine deaminase inhibitor (1 and 10 mg/kg, i.p.) also caused an antidepressant-like effect in the FST. These results indicate that inosine possesses an antidepressant-like effect in the FST and TST probably through the activation of adenosine A₁ and A_2A receptors, further reinforcing the potential of targeting the purinergic system to the management of mood disorders.     

Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration

AimsThe objective of this work was to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), after their intraperitoneal administration in male and female mice.Main methodsAfter single administration of free CDDP (5,10,and 20 mg/kg) or SpHL-CDDP (7,12,30,45 and 80 mg/kg), the body weight was recorded and the LD₅₀ was calculated. Blood samples were collected for biochemical and hematological analysis. Kidneys, liver, spleen and bone marrow were removed to histopathological examination.Key findingsMice treated with high doses of free CDDP showed a greater loss of body weight and more delayed recovery time than those treated with SpHL-CDDP. The LD₅₀ values for SpHL-CDDP treatment for male and female mice groups were 2.7 and 3.2 fold higher, respectively, than that obtained for free CDDP. The red and white blood cells counts and quantification of hemoglobin and hematocrit presented no change upon administration of SpHL-CDDP treatment. Free CDDP treatment, however, did lead to an appearance of mild anemia and a reduction in total white blood cell counts. As regards nephrotoxicity, it was observed that free CDDP treatment caused pronounced alterations in the blood urea and creatinine levels of mice. In contrast, these parameters were slightly altered only after SpHL-CDDP treatment at a dose of 30 mg/kg. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed no morphological alteration. Concerning hepatotoxicity, no histopathological alteration was observed after both treatments.SignificanceThese findings reveal that SpHL-CDDP can eliminate CDDP-induced toxicity and is thus a promising candidate for intraperitoneal chemotherapy.     

Genetic Effects Induced by Nickel Sulfate in Germline and Somatic Cells of WR Mice

We examined the effects of nickel sulfate at doses 0.5 to 5.0 mg/kg (1/200–1/20 LD₅₀) on the frequency of dominant lethal mutations and double-strand DNA breaks (DSBs) in germline cells and on an increase in frequency in gene mutations W ^y in pigment cells of first-generation mice. The results indicated that spermatogenesis stages most sensitive to nickel sulfate (at a dose of 1.0 mg/kg) are spermatozoids, early spermatids, late spermatocytes, and stem spermatogonia. No statistically significant increase in the total TSB level was detected in spermatozoids 4 weeks after exposure. At the same time, a significant (P < 0.05) increase in percentage of cells with an extremely high level of DNA fragmentation (supposedly apoptotic cells) was observed upon exposure at a dose of 0.5 mg/kg. Nickel sulfate at doses of 5.0 and 1.0 mg/kg induced a marked increase in the c-kit gene expression in pigment cells of heterozygous first-generation WR mice as compared to control (P < 0.001). It was shown that the nonobservable adverse effect level (NOAEL) of nickel sulfate on the dominant lethal mutation frequency and gene mutations was 1/200 LD₅₀, while the lowest observable adverse effect level (LOAEL) was 1/100 LD₅₀.__________Translated from Genetika, Vol. 41, No. 7, 2005, pp. 894–901.Original Russian Text Copyright © 2005 by Domshlak, Elakov, Osipov.     

Lethal Effect of Neutral Mannan Fraction of Bakers' Yeast in Mice

A simple polysaccharide, the neutral mannan from Saccharomyces cerevisiae wild type strain (WNM) was found to kill ddY strain mice by intravenous administration, showing a LD₅₀ value of 12.2 mg/kg. On the other hand, the acidic mannan fraction from the same yeast containing phosphate (WAM025), and chemically phosphorylated WNM (WNM-P) were practically non-toxic. Concerning the relationship between chemical structure and lethal effect of these mannans, it was demonstrated that a mannan possessing a highly branched structure exhibited stronger lethality than those with less branched structures. Against C3H/HeJ strain mice with no responsiveness to lipopolysaccharide, the LD₅₀ value of WNM was as high as 75 mg/kg. Pretreatment with 500 mg/kg of D-mannose, N-acetyl-D-glucosamine, D-galactose, and L-fucose prevented mice from the lethal effects of WNM. However, WNM (LD₁₀₀) did not show any lethal effect in mice for 2 to 12 hr after treatment with dexamethasone, an anti-inflammatory steroid.     

Additional phytoalexin-like compounds in Ht-gene resistance of corn to Helminthosporium turcicum

Four additional compounds inhibitory to germination of Helminthosporium turcicum spores were isolated from lesion-extracts of field-grown Ht-gene corn (Zea mays) lines which were inoculated with H. turcicum. The compounds were named phytoalexins A₃, A_4-I, A_4-II and A₅. A₃, A_4-1 and A_4-1 showed over 99% inhibition of H. turcicum spores at 1 mg/ml of 10% ethanol and LD₅₀ of about 600 μg/ml. A₅ showed an LD₅₀ of about 800 μg/ml of 10% ethanol. The ultraviolet, infrared, nuclear magnetic resonance, electron impact mass spectra and field desorption mass spectra showed that these compounds might be related to the previously described phytoalexins A₁ and A₂. They seem to have the following functional groups: aromatic ring, hydroxyl and/or phenolic groups, carbonyl groups, probably a carboxylic acid or ester type and a long aliphatic side chain.     

Toxic Blue-green Algae Water Blooms Found in some Lakes in the German Democratic Republic

From 1977 to 1979 plankton samples were taken from 6 lakes in the German Democratic Republic (GDR) during water blooms and examined for their toxicity to homothermal animals. Microcystis aeruginosa, Aphanizomenon flos-aquae, Anabaena spiroides, and Oscillatoria redekei were dominant in the samples. With the exception of Oscillatoria redekei the algae tested had toxic effects on mice after intraperitoneal injection. The rate of survival of the test animals was particularly low when the algae were disintegrated by ultrasound or freeze-drying prior to injection, this indicating the endogenic character of the toxins. Water blooms of Microcystis aeruginosa taken from Lake Pehlitzsee (Eberswalde District) showed the highest toxicity with an LD₃₀ as high as 45 and 43.7 mg/kg, respectively. Injection of the lyophilized cells of Aphanizomenon flos-aquae brought about the same symptoms in the test animals as in the case of Microcystis, but the LD₃₀ was 200 mg/kg.     

Studies on the Utilization of Levulinic Acid

The single injection of levulinic acid oxime (250 mg/rat) or α-ketoglutaric acid oxime (250 mg/rat) on rats, carrying radioactive cesium, promoted both urinary and fecal excretion of this radionuclide. The administration of levulinic acid oxime (sodium salt) decreased the cesium retention by liver. The administration of the oxime did not have influence on the urinary excretion of sodium and potassium in normal rats. The toxicity of the oxime was low. The LD₅₀ of α-ketoglutaric acid oxime was 3500 mg/kg (mice, intraperitoneally). (The LD₅₀ of levulinic acid oxime has already been indicated as 2040 mg/kg (mice, intravenously).     

Efficacy of various synthetic pyrethroid-impregnated encasement materials against house dust mite under laboratory conditions

The acaricidal activity of synthetic pyrethroid and benzyl benzoate against Dermatophagoides pteronyssinus was examined in the laboratory, using a specially designed test set up. On the basis of median lethal dose (LD₅₀) values, the compound found to be most toxic to D. pteronyssinus was benzyl benzoate (LD₅₀ = 50 mg/m²), followed by permethrin (LD₅₀ = 76.7 mg/m²), deltamethrin (LD₅₀ = 146.7 mg/m²), esbioallenthrin (LD₅₀ = 186.6 mg/m²) and lamdacyhalothrin (LD₅₀ = 756.6 mg/m²). Very low toxicity was observed with bifenthrin (LD₅₀ = 5157.8 mg/m²). A laboratory control trial was also carried out to compare the acaricidal activity (residual effect) of four pyrethroids impregnated on woven and non-woven encasement materials against house dust mites during a 4-month period. Of the pyrethroids used in this study, esbioallenthrin demonstrated the highest acaricidal activity, and of the pyrethroid impregnated materials, the non-woven encasement material was more effective than the woven encasement material.     

A toxic substance produced by Nocardia otitidiscaviarum isolated from cutaneous nocardiosis

During our studies on toxic substances from clinically isolated Nocarida, a new isolate identified as Nocardia otitidiscaviarum from cutaneous nocardiosis was found to produce a toxic substance called HS-6 that had strong in vitro as well as in vivo toxicity. The mouse intraperitoneal LD₅₀ value was 1.25 mg/kg and the ED₅₀ value for L1210 cultured cells was 0.3 ng/ml. The structure of HS-6 was determined and found to belong to the 16-membered macrocyclic group with a molecular formula of C₄₃H₆₈O₁₂. HS-6 also showed activity against pathogenic fungi such as Cryptococcus neoformans.     

Detection and characterization of naturally occuring plasmids in Bacillus subtilis

Summary A rapid procedure has been employed to isolate a large number of mitochondrial mutants resistant to antimycin A or funiculosin. A total of 15 antimycin A resistance mutations has been mapped by allelism tests. The mutations belong to two new mitochondrial loci, designated A_I and A_II. All funiculosin resistance mutations studied up to now map at locus A_II. Thus mitochondrial funiculosin resistance might allow the specific selection of mutations in A_II. Recombination between the two antimycin A resistance loci A_I and A_II occurs at frequencies from 8 to 21%. Apparently the two loci are not linked to PAR1, RIB1, RIB3, OLI1, and OLI2. Mutants of the two loci A_I and A_II have been characterized by measurements of oxygen consumption. Analysis of cytochrome spectra indicates that the mutations affect the cytochrome bc₁ complex of the mitochondrial respiratory chain.     

Acute administration of levetiracetam in tonic pain model modulates gene expression of 5HT1A and 5HT7 receptors in the thalamus of rats (Rattus norvergicus)

The nociceptive effect of Levetiracetam (LEV) on the expression of 5-HT_1A and 5-HT₇ receptors found in the thalamus was evaluated. Thirty-six male rats (Wistar) were randomized into six groups: in the Control group without treatment; LEV50 group LEV was administered in a single dose of 50 mg/kg i.g.; in the LEV300 group LEV dose of 300 mg/kg i.g.; in the FORMALIN group the formalin test was performed; in the LEV50/FORMALIN group LEV dose of 50 mg/kg i.g and the formalin test was performed; in the LEV300/FORMALIN group LEV dose of 300 mg/kg i.g and the formalin test was performed, subsequently the thalamus was dissected in all groups. In the formalin tests LEV exhibited an antinociceptive effect in the LEV300/FORMALIN group (p?<?0.05) and a pronociceptive effect in the LEV50/FORMALIN group (p?<?0.001). The results obtained by Real-time PCR confirmed the expression of the 5-HT_1A and 5-HT₇ receptors in the thalamus, 5-HT_1A receptors increased significantly in the FORMALIN group and the LEV300/FORMALIN group (p?<?0.05). 5-HT7 receptors are only over expressed at a dose of 300 mg/Kg of LEV with formalin (p?<?0.05). This suggests that LEV modulates the sensation of pain by controlling the expression of 5-HT_1A and 5-HT₇ in a tonic pain model, and that changes in the expression of 5-HT_1A and 5-HT₇ receptors are associated with the sensation of pain, furthermore its possibility to be used in clinical treatments for pain.

     

Design of liposomes to improve delivery of amphotericin-B in the treatment of aspergillosis

The efficacy and toxicity of free and liposome intercalated amphotericin-B (Amp-B) in controlling Aspergillosis, caused byAspergillus fumigatus in BALB/c mice were studied. Liposomal Amp-B had higher LD₅₀ (8.1 mg/kg) as compared to that of the free drug (1.2 mg/kg). An improvement in the therapeutic index of the drug was observed with liposomal formulation of the drug. We also focussed on the effect of lipid composition and surface sugar in modulating the therapeutic potency of Amp-B. The most effective liposomal preparation was composed of egg phosphatidylcholine (EPC) : L--phosphatidylethanolamine, dipalmitoyl (DPPE): cholesterol (Chol) in the molar ratio of 6:1:3. Amp-B intercalated into mannose grafted liposomes (LD₅₀ = 9.3 mg/kg) was more effective as compared to the other formulation tested.     

A Study on the Safety and Effects of Amorpha fruticosa Fruit Extract on Spontaneously Hypertensive Rats with Induced Type 2 Diabetes

Metabolic syndrome is characterized by a variety of diagnostic criteria: obesity, dyslipidemia, type 2 diabetes, and arterial hypertension. They contribute to the elevated risk of cardiovascular morbidity and mortality. The potential for Amorpha fruticosa L. (Fabaceae) to improve diabetes and metabolic disease is promising, based on in vitro tests. This is why a further investigation of the species is needed. Additionally, a toxicity review in relation to safety revealed that to date, there are no published data regarding the toxicity of A. fruticosa towards humans. This species could provide abundant and cheap resources because it is an aggressive invasive plant that grows almost unrestrictedly. The objective of this study was to evaluate the acute toxicity of a purified extract of A. fruticosa (EAF), and to assess its antioxidant, antihypertensive, and antihyperglycemic activity in streptozotocin-induced diabetic spontaneously hypertensive rats (SHRs). The EAF was slightly toxic (LD₅₀ = 2121 mg/kg, b.w.) when administered orally, and moderately toxic (LD₅₀ = 316 mg/kg, b.w.) at intraperitoneal administration, both in mice. The oral administration of EAF (100 mg/kg) for 35 days to SHRs caused significant decreases in the systolic pressure, blood glucose levels, and MDA quantity. It also increased the hepatic level of the endogenous antioxidant GSH, not only in diabetic SHRs, but also in the control group. An additional potential benefit to human health might be conferred through the environmental management of A. fruticosa based on its large-scale use for medicinal purposes, as this aggressive invasive species brings problems to natural habitats in many European countries.     

Fumigant Toxicity of Plant Essential Oils to Plutella xylostella (Lepidoptera: Yponomeutidae) and Cotesia glomerata (Hymenoptera: Braconidae)

The fumigant toxicity of 66 plant essential oils to Plutella xylostella (L.) larvae and Cotesia glomerata (L.) adults was examined using a vapor-phase toxicity bioassay and compared with that of dichlorvos. Responses varied according to oil and insect species used. Based on 24 h LD₅₀ values, pennyroyal oil [10.77 mg/filter paper (4.25 cm diameter)] was the most toxic fumigant, followed by rosemary and sage (Dalmatin) oils (15.15 mg/paper). Potent fumigant toxicity was also produced from armoise, buchu leaf, cedarleaf, coriander, eucalyptus, howood, lavender, myrtle, niaouli, peppermint, and rosewood oils (LD₅₀, 21.29–27.31 mg/paper). All essential oils were less effective than dichlorvos (LD₅₀, 0.52 mg/paper). Against adult C. glomerata, dichlorvos (LD₅₀, 0.03 mg/paper) was the most toxic fumigant, whereas the LD₅₀ values of the 14 essential oils ranged from 1.59 to 8.51 mg/paper. Based on selective toxicity ratio (STR, P. xylostella LD₅₀/C. glomerata LD₅₀), the 14 essential oils (STR, 2.5–14.5) are more selective than dichlorvos (STR, 17.3). The essential oils tested merit further study as potential fumigants for the control of P. xylostella in greenhouses because of their selective toxicity to adult C. glomerata and their much greater activity as a fumigant.     

Efficacy and safety of catnip (Nepeta cataria) as a novel filth fly repellent*

Catnip (Nepeta cataria) is known for its pseudo‐narcotic effects on cats. Recently, it has been reported as an effective mosquito repellent against several Aedes and Culex species, both topically and spatially. Our laboratory bioassays showed that catnip essential oil (at a dosage of 20 mg) resulted in average repellency rates of 96% against stable flies, Stomoxys calcitrans (L.) and 79% against houseflies, Musca domestica (L.), respectively. This finding suggested that the application of repellent could be used as part of filth fly management. Further evaluations of catnip oil toxicity were conducted to provide a broad‐spectrum safety profile of catnip oil use as a potential biting and nuisance insect repellent in urban settings. Acute oral, dermal, inhalation, primary dermal and eye irritation toxicity tests were performed. The acute oral LD₅₀ of catnip oil was found to be 3160 mg/kg body weight (BW) and 2710 mg/kg BW in female and male rats, respectively. The acute dermal LD₅₀ was > 5000 mg/kg BW. The acute inhalation LD₅₀ was observed to be > 10 000 mg/m³. Primary skin irritation tested on New Zealand white rabbits showed that catnip oil is a moderate irritant. Catnip oil was classified as practically non‐irritating to the eye. In comparison with other U.S. Environmental Protection Agency‐approved mosquito repellents (DEET, picaridin and p‐menthane‐3,8‐diol), catnip oil can be considered as a relatively safe repellent, which may cause minor skin irritation.     

In Silico,In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH<Subscript>2</Subscript>, A Vasoactive Proline-Rich Oligopeptide from <Emphasis Type="Italic">Brachycephalus ephippium</Emphasis>

BPP-BrachyNH₂ is a proline-rich oligopeptide (PRO) firstly identified in skin secretion of the frog Brachycephalus ephippium, which possess in vitro inhibitory activity of angiotensin-I converting enzyme (ACE) and endothelium-dependent vasorelaxant activity. Considering its potential application in the treatment of cardiovascular diseases, the present work assessed the toxicological profile of the BPP-BrachyNH₂. The in silico toxicity prediction was performed from the best model obtained through the optimization of the FASTA query peptide. This prediction study revealed that BPP-BrachyNH₂ induced high predicted LD₅₀ values for both humans and rats, and then is well-tolerated in the recommended range. The MTT assay was applied for the in vitro cytotoxic evaluation in murine macrophages. In this assay, a decrease of cell viability was not observed. The in vivo acute toxicological study was performed after the intraperitoneal administration of BPP-BrachyNH₂ at doses of 5 and 50 mg/kg. After intraperitoneal administration, no death, alterations in behavioral parameters or weight gain curve was observed, as well as none in the serum biochemical parameters, and gross pathological and histopathological analyses. These observations demonstrates an acceptable safety profile for BPP-BrachyNH₂, leading towards further studies focused on investigation of pharmacological and therapeutical applications for this peptide.     

Effect of Some Variables on theIn VivoDetermination of Scorpion and Viper Venom Toxicities

An adequate assessment of scorpion and snake venom LD₅₀is an important step for accurate evaluation of antivenom sera potencies and the optimization of serotherapy. The LD₅₀variation of Tunisian scorpion (Androctonus australis garzonii: Aag andButhus occitanus tunetanus: Bot) venoms with body weight, sex and strain (Swiss or C57Bl/6) of mice used, the route of venom injection, the venom-milking procedures (manually or electrically) and the venom batches have been studied over a 7-year period (1990–1996). Aag venom is 3–4 times more toxic than Bot venom. However for both venoms, the LD₅₀determined in C57Bl/6 mice, in small body weight animal or by intraperitoneal route were respectively significantly lower than those determined in Swiss mice, in high body weight or by subcutaneous route. Significant LD₅₀variations (25–50%) were also seen from one electrically prepared batch to another. A good correlation (r=0·982) was observed between the concentrations of the crude venom toxic fraction determined by ELISA and LD₅₀values when assessedin vivo.The LD₅₀variation of Tunisian viper (Cerastes cerastes: Cc andVipera lebetina: VI) venoms with the strain (Swiss or BALB/c), sex and body weight of mice used, the season and the year of venom milking were also investigated over a 3-year period (1990–1992). No significant LD₅₀variations were observed with the mouse strain, the sex or the season of venom milking. However, LD₅₀varies significantly with the year of the venom collection and the body weight of mice used. Furthermore, SDS–PAGE analysis shows annual variation for VI venom composition where no such variations were observed for Cc venom. These results stress the need either for the standardization of the venom LD₅₀evaluation or the venom quality used for the development of an efficient antivenom.     

Histopathological and biological studies of the effect of cadmium on Rhinella arenarum gonads

This study was to determine the lethal dose 50 (LD₅₀) of CdCl₂ in adult Rhinella arenarum and analyzed the effect of two sublethal doses (0.5 and 5 mg/kg) of the xenobiotic in gonads. The 48 h LD₅₀ were 50.0 and 49.8 mg/kg for males and females respectively. Alterations in the ovary were evidenced by nuclear pleomorphism and cytoplasmic vacuolization of the oocytes at the early stages of development with the highest dose and an increase in the population of atretic oocytes. In the interstitial tissue we noticed congestion, edema and fibroblast proliferation. The nuclear maturation of the oocytes was affected by the xenobiotic in a dose- and time-dependent manner. In males, treatment with 5 mg/kg of cadmium (Cd) caused a decrease in the concentration, viability and straight progressive motility of sperm while there was an increase in immotile sperm. Testis histopathology revealed dilated seminiferous tubules, disappearance of cysts, tissue disorganization and leukocyte infiltration. Numerous germ cells showed hydropic tumefaction or signs of focal necrosis. The Cd content in animals intoxicated gonads with the highest sublethal dose was significantly higher than in the control. Results indicate that R. arenarum gonads are target for the xenobiotic, compromising the formation of gametes competent for fertilization, the effective CdCl₂ dose being 5 mg/kg.     

Toxicity and Immunogenic Properties of Liposomal form of Vipera Libetina Venom

Abstract

The incorporation of Vipera libetina venom into liposomes obtained from pure egg phosphatidyl choline by the reverse phase evaporation method decreases its toxicity by 3-fold - in mice LD₅₀ for the native toxin is 2.22 mg/kg body weight and for the liposomal toxin 6.9 mg/kg. Subcutaneous injection of liposomal preparation into mice stimulates the development of cellular immunity and reproduces the reaction of the delayed-type hypersensitivity. It is. also, shown that after a single dose immunization of mice with liposomes containing 1xLD₅₀ dose of the venom, the.titer.of antibodies increases at the early postinfection period and is maintained on high level longer than after the injection of the native venom. Thus, liposom.es can be succesfully used for antiserum production and protective immunization against Vipera libetina venom.     

Efficacy of Cyclooctadepsipeptides and Aminophenylamidines against Larval,Immature and Mature Adult Stages of a Parasitologically Characterized Trichurosis Model in Mice

Background

The genus Trichuris includes parasites of major relevance in veterinary and human medicine. Despite serious economic losses and enormous impact on public health, treatment options against whipworms are very limited. Additionally, there is an obvious lack of appropriately characterized experimental infection models. Therefore, a detailed parasitological characterization of a Trichuris muris isolate was performed in C57BL/10 mice. Subsequently, the in vivo efficacies of the aminophenylamidines amidantel, deacylated amidantel (dAMD) and tribendimidine as well as the cyclooctadepsipeptides emodepside and in particular PF1022A were analyzed. This was performed using various administration routes and treatment schemes targeting histotropic and further developed larval as well as immature and mature adult stages.

Methodology/Principal Findings

Duration of prepatent period, time-dependent localization of larvae during period of prepatency as well as the duration of patency of the infection were determined before drugs were tested in the characterized trichurosis model. Amidantel showed no effect against mature adult T. muris. Tribendimidine showed significantly higher potency than dAMD after oral treatments (ED₅₀ values of 6.5 vs. 15.1 mg/kg). However, the opposite was found for intraperitoneal treatments (ED₅₀ values of 15.3 vs. 8.3 mg/kg). When emodepside and PF1022A were compared, the latter was significantly less effective against mature adults following intraperitoneal (ED₅₀ values of 6.1 vs. 55.7 mg/kg) or subcutaneous (ED₅₀ values of 15.2 vs. 225.7 mg/kg) administration. Only minimal differences were observed following oral administration (ED₅₀ values of 2.7 vs. 5.2 mg/kg). Triple and most single oral doses with moderate to high dosages of PF1022A showed complete efficacy against histotropic second stage larvae (3×100 mg/kg or 1×250 mg/kg), further developed larvae (3×10 mg/kg or 1×100 mg/kg) and immature adults (3×10 mg/kg or 1×100 mg/kg). Histotropic first stage larvae were only eliminated after three doses of PF1022A (3×100 mg/kg) but not after a single dose.

Conclusions/Significance

These results indicate that the cyclooctadepsipeptides are a drug class with promising candidates for further evaluation for the treatment of trichurosis of humans and livestock animals in single dose regimens.