Assessment of the effective dose of an experimental intramuscular formulation against immature and adult Fasciola hepatica in sheep.

The effective dose of an injectable prodrug, named compound alpha prodrug, against immature and adult Fasciola hepatica in experimentally infected sheep was determined. In a first experiment, 30 sheep were infected with Fasciola hepatica on day 0 and 50. After microscopic detection of faecal eggs on day 80, groups (n = 6) 1 to 3 were treated with 6, 8 and 10 mg/kg of the experimental water-soluble prodrug compound alpha intramuscularly, respectively. Group 4 was treated with closantel and group 5 remained untreated. Copromicroscopical examinations were made on day 0, 80 and 108. On day 110, trematodes were collected from the bile ducts. Fasciolicide efficacy was assessed as a percentage of fluke-egg and adult-fluke reduction. Fluke length was also recorded. In a second experiment aimed to assess the fasciolicide activity of compound alpha prodrug against four-week-old flukes, 12 sheep were infected on day 0 and allocated into two groups (n = 6). On day 50 post infection, group A was treated with the experimental water-soluble prodrug compound alpha at 6 mg/kg/IM and B remained untreated. Fasciolicide activity was assessed on day 80 after collection, microscopic observation and measurement of flukes present in the parenchyma for immature stages and on day 108 for adults. Egg output decreased 91.2, 96.0, 98.8 and 94.9% for groups 1, 2, 3 and 4, respectively. Compound alpha prodrug cleared 97.6%, 98.51% and 100% of adult stages in a dose-dependent manner. Closantel killed 81.95% flukes. Regarding the second experiment, 81.2% efficacy was achieved. Immature flukes were significantly smaller in the treated group. It is concluded that the intramuscular application of compound alpha prodrug exerted fasciolicide efficacy against adults of Fasciola hepatica.

Variantes anatómicas del septum pellucidum / Anatomical variations of septum pellucidum

El septum pellucidum es un fino tabique formado por dos láminas gliales dispuestas entre el cuerpo calloso en dirección cefálica y el trígono ubicado caudalmente. Durante la vida embrionaria existen variantes anatómicas del septum pellucidum que se disponen en sentido rostro-dorsal. Estas son el cavum del septum pellucidum, el cavum vergae yel cavum velum interpositum. Su presencia o ausencia puede estar relacionada con alteraciones del desarrollo del sistema nervioso y trastornos cognitivo-psiquiátricos, por lo que deben conocerse bien para evitar diagnósticos erróneos

Septum pellucidum consists of a two thin laminae situated caudal to the corpus callosum and cephalic to the fornix (trigonum). Anatomical variations of septum pellucidum appear during fetal life in the ventro-dorsal position. These variations are: cavum septi pellucidi, cavum vergae and cavum veli interpositi. The presence or absence of these cavities can be related to the presence of nervous system or neuropsychiatric dysfunction, therefore they have to be well known to avoid a wrong diagnoses

Pivotal role of protein tyrosine phosphatase 1B (PTP1B) in the macrophage response to pro-inflammatory and anti-inflammatory challenge.

Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been suggested as an attractive target to improve insulin sensitivity in different cell types. In the present work, we have investigated the effect of PTP1B deficiency on the response of human and murine macrophages. Using in vitro and in vivo approaches in mice and silencing PTP1B in human macrophages with specific siRNAs, we have demonstrated that PTP1B deficiency increases the effects of pro-inflammatory stimuli in both human and rodent macrophages at the time that decreases the response to alternative stimulation. Moreover, the absence of PTP1B induces a loss of viability in resting macrophages and mainly after activation through the classic pathway. Analysis of early gene expression in macrophages treated with pro-inflammatory stimuli confirmed this exacerbated inflammatory response in PTP1B-deficient macrophages. Microarray analysis in samples from wild-type and PTP1B-deficient macrophages obtained after 24 h of pro-inflammatory stimulation showed an activation of the p53 pathway, including the excision base repair pathway and the insulin signaling pathway in the absence of PTP1B. In animal models of lipopolysaccharide (LPS) and D-galactosamine challenge as a way to reveal in vivo inflammatory responses, animals lacking PTP1B exhibited a higher rate of death. Moreover, these animals showed an enhanced response to irradiation, in agreement with the data obtained in the microarray analysis. In summary, these results indicate that, although inhibition of PTP1B has potential benefits for the treatment of diabetes, it accentuates pro-inflammatory responses compromising at least macrophage viability.

Efficacy of an experimental fasciolicide against immature and mature Fasciola hepatica in artificially infected calves.

The efficacy of 5-chloro-2-methylthio-6-(1-naphthyloxy)- 1H-benzimidazole, called "alpha", was tested against Fasciola hepatica. Fluke-free calves ( n=32) were divided into 8 groups and infected with 150 metacercariae per animal. All animals subsequently received a second infection with another 150 metacercariae, given at different time intervals aimed to produce flukes of differing ages within the experimental animals. When the flukes reached the required age in the animals, four groups were treated with a single oral dose of 12 mg/kg of compound alpha and the remaining ones served as non-treated controls. Two weeks after treatment the animals of all groups were sacrificed and the livers were removed to determine the numbers of parasites present in the treated and untreated controls. In the treated groups the fluke reduction for the 3 day/2 week group was 100%, for the 3 week/4 week group it was 96.4%, for the 6 week/8 week group it was 99.2% and for the 10 week/12 week group it was 100%.

Field trial on the efficacy of an experimental fasciolicide compared with some commercial compounds in naturally infected cattle.

The efficacy of 5-chloro-2-methylthio-6-(1-napthyloxy)-1H-benzimidazole was evaluated with three commercial fasciolicides in terms of the percentage of egg reduction in cattle. Fifty Swiss cows were selected for inclusion in the trial based on finding eggs of Fasciola hepatica in their feces. On day 0, they were blocked in five groups (G) of ten animals each according to fecal egg counts. G1 received compound alpha at 12 mg/kg p.o.; G2 triclabendazole at 12 mg/kg p.o.; G3.closantel at 3.5 mg/kg s.c.; G4 clorsulon at 2.0 mg/kg s.c. G5 animals served as untreated controls. Fecal analysis was performed on days 0, 7, 14, 21, 28, 60 and 90. Efficacy was measured on days 14 and 21. In addition, the extension and intensity effects were determined on day 60. The percentage efficacy for groups 1-4 was 98.1, 98.7, 98.2 and 97.9 on day 14 and 98.5, 97.9, 97.7 and 97.9 on day 21, respectively. No statistical differences were observed between treated groups.

Comportamiento del cáncer colorrectal en pacientes menores de cuarenta años deñ Hospital Universitario Hernando Moncaleano Perdomo de Neiva (HUHMP) y el Hospital Universitario San Vicente de Paul de Medellín (HUSVP) entre 1980 y 2000 / Clinical behavior of colorectal cancer in patients less than 40 years of age in Neiva and Medellín, Colombia, in 1980-2000

Objetivo: Determinar el comportamiento del cancer colorectal (CCR) en pacientes menores de 40 años diagnosticados en el HUHMP y el HUSVP entre los años 1980 y 2000. Metodologia: Estudio de tipo descriptivo retrospectivo. La recoleccion de datos se realizó a partir de las historias clinicas, previa revision de los informes de patologia en cada una de las instituciones. Resultados: La frecuencia del CCR en el HUHMP fue del 20.9 vs 21.9 por ciento en el HUSVP, con un promedio de edad de 28 y 30 años respectivamente, confirmando la alta incidencia de la enfermedad en menores de 40 años en nuestro pais con respecto a lo informado mundialmente (21 por ciento vs 5 por ciento). Las lesiones se localizaron principalmente en el recto. Los sintomas más frecuentes fueron dolor abdominal, sangrado rectal y perdida de peso; el diagnostico fue realizado en los estadios Dukes C y D, indicando que en personas jovenes el diagnostico se realiza generalmente en forma tardia. Conclusion: En nuestra poblacion, la frecuencia de CCR en personas jovenes es la mas altas informada en el mundo.

Cáncer colo-rectal heredado / Hereditary colo-rectal cancer

El 15 por ciento de los CCR, está asociado con un patron de herencia autosomico dominante y se estima que aproximadamente 12.940 nuevos casos y 6.580 definiciones tienen antecedentes familiares. Por lo tanto, el factor genetico atribuido a su etiologia se considera cada vez de una mayor importancia. Gracias a los grandes avances de la biologia molecular durante la pasada decada, se propuso la perdida de heterocigocidad y la presencia de mutaciones germinates en el sistema de reparacion del ADN como mecanismos que predisponen al CCR. La Poliposis Adenomatosica Familiar (FAP) causada por el primer mecanismo se presenta en menos del 1 por ciento de todos los casos de CCR, mientras que el segundo mecanismo (CCNPH) ocasiona entre el 10 y 15 por ciento.

Efficacy of combined chemotherapy against gastrointestinal nematodes and Fasciola hepatica in cattle.

A controlled trial of the efficacy of several anthelmintic compounds as a combined therapy in the treatment of gastrointestinal nematodes (GIN) and Fasciola hepatica (F. hepatica) in naturally infected cattle was carried out. Twenty crossbred calves, 8-18 months old, were selected for inclusion in the trial based on finding eggs of F. hepatica and GIN in the faeces. They were blocked in four groups of five animals each according to GIN fecal egg counts on day 0. Treatments were sequentially allocated to animals in each block as follows: Group 1 served as non-treated control; Group 2 was treated with netobimin orally at 20 mg/kg; Group 3 received triclabendazole orally at 12 mg/kg and levamisole was applied intramuscularly at 5.5 mg/kg; Group 4 received clorsulon administered subcutaneously (s.c.) at 2 mg/kg and ivermectin s.c. at 200 microg/kg. Six to eight days after treatment the animals were euthanatized in order to collect and identify the parasites. Results showed a reduction of GIN by 87.3, 95.8 and 99.5% in Groups 2, 3 and 4, respectively. The percentage reduction of immature flukes was 0.0, 72.5, and 67.5% and for adult flukes 91.0, 97.5 and 100% for Groups 2, 3 and 4, respectively. Compounds indicated against nematodes showed high efficacy and products directed against F. hepatica acceptably removed adult flukes. However, efficacy against immature stages was generally not satisfactory.

[Fasciolinip-1: experimental fasciolicidal activity in sheep]. / Fasciolinip-1: eficacia fasciolicida experimental en ovinos.

The aim of the present study was to evaluate the flukicide efficacy of the 2-amino-5(6)-chloro-1-methoxycarbonylbenzimidazole (II), named Fasciolinip-1, against eight and twelve-week old flukes in sheep. In a first experiment 35 young sheep were infected each with 300 metacercariae of Fasciola hepatica. Eight weeks postinfection five groups of seven animals each were treated as follows: Groups 1, 2 and 3 were given 2.5, 5 and 10 mg/kg of Fasciolinip-1. Groups 4 and 5 remained as non-treated and vehicle controls, respectively. In a second study, 32 sheep were infected each with 150 metacercariae. Twelve weeks postinfection, the animals were divided into 4 groups of 8 sheep each. Groups 1, 2 and 3 were treated orally with 5, 10 and 15 mg/kg of Fasciolinip-1, respectively. Group 4 remained as non-treated control. Fifteen days after treatment, all sheep from both experiments were killed to collect the flukes present in liver. Results indicated efficacies of 19.1%, 49.6% and 65.2% for groups 1, 2 and 3 of the first study and 48.3%, 64.8 and 90.6% for sheep of the second experiment, respectively. It was concluded that Fasciolinip-1 removed 8-week old flukes in limited numbers and 12-week old flukes in 90.6% when used at 15 mg/kg body weight.

[Evaluation of chemotherapeutic agents against cichlidogyriasis in tilapia (Oreochromis hornorum) in Mexico]. / Evaluación de quimioterapéuticos contra la ciclidogiriasis en tilapia (Oreochromis hornorum) en México.

To evaluate the efficacy of seven compounds against the cichlidogyriasis of tilapia fish (Oreochromis hornorum), two experiments were carried out. In one, 160 naturally infected fish with a mean burden of 33.4 parasites/animal were used. In another, 1600 fish with a burden of 49.9 parasites/fish were used. Fish were randomly divided into eight equal groups and received three treatments as submersion baths: methylene blue, malachite green, potassium permanganate, sodium chloride, formaldehyde, copper sulfate and triclorfon, and a non-treated control. Five days after the last treatment, all fish were killed and dissected to quantify the remaining parasites. All data were submitted to an ANOVA analysis. All groups compared to the control showed statistical difference (P < 0.01), with better efficacy at higher doses. Sodium chloride, potassium permanganate and triclorfon are highly efficient in the control of cichlidogyriasis of tilapia fish, but care should be taken with the toxicity of the two first compounds.

[Evaluation of 4 vermifuges against Bothriocephalus acheilognathi in carp]. / Evaluación de cuatro vermicidas contra Bothriocephalus acheilognathi en carpas.

With the aim to evaluate the efficacy of four vermicides, praziquantel, mebendazole, nitroscanate and triclorfon in the control of Bothriocephalus acheilognathi in carps, one hundred and sixty, two year-old carps (Ctenopharyngodon idellus) with an average weight of 120 g and a mean parasitic burden of 115.5 parasites/fish were used. Five groups of 30 fish each were randomly formed. Each group was then subdivided in three groups, each of 10 individuals/pond. The three subgroups of group A received 30, 50 and 70 mg/Kg of praziquantel, respectively. Groups B and C received 2.2, 4.4, and 6.8 mg/Kg of mebendazole suspension and mebendazole solution respectively; groups D and E received 10, 30, 50 mg/Kg; and 2.0, 4.0, 6.0 mg/Kg of nitroscanate and trichlorfon respectively. Group F of 10 fish remained as non-treated control. Praziquantel showed 100% of efficacy for all doses, therefore it was excluded from the statistical analysis. The subgroups B, C, D and E compared with the non-treated control were statistically significant (P < 0.01); showing in all treatments an additive effect, the higher the dose the better efficacy, except trichlorfon which showed a different tendency, having no explanation on that matter.