Intratumoral recombinant human interferon alpha-2a and vincristine combination therapy in canine transmissible venereal tumour.

Canine transmissible venereal tumour (CTVT) is a naturally occurring contagious neoplasm of dogs located mainly on the external genitalia of both sexes. The course of vincristine chemotherapy, the most effective and practical therapy, is affected by the immune status of the host. The aim was to investigate recombinant human interferon alpha-2a (rhIFNα-2a) and vincristine for treatment of CTVT. A total of 21 female dogs were included. In group I (n = 9), vincristine (0.025 mg/kg, IV) was administered weekly. In group II (n = 6), dogs were injected intratumorally weekly with 1.5 million IU rhIFNα-2a. In group III (n = 6), rhIFNα-2a and vincristine were combined. No tumour regression was observed after three injections of rhIFNα-2a in group II and weekly vincristine was administered. The number of tumour infiltrating lymphocytes (TILs), mitotic figures and apoptotic cells were counted in subsequent incisional tumour biopsies. The Kaplan-Meier Method was used to analyse survival using complete tumour regression as the outcome and Breslow Test was used for comparison of survival curves. Differences in TILs, cell proliferation and apoptosis between groups were assessed by analysis of covariance. Complete regression was observed in all animals included. Mean duration of vincristine treatment for complete regression was shorter in group II (3.50 weeks, 95% CI, 3.06-3.94, P < 0.05) and group III (3.17 weeks, 95% CI, 2.84-3.49, P < 0.01) compared to group I (5.11 weeks, 95% CI, 4.42-5.80). Vincristine and rhIFNα-2a combination increased TILs in CTVT biopsies compared to vincristine treatment (P = 0.017) and vincristine treatment after rhIFNα-2a (P = 0.049). Vincristine treatment after rhIFNα-2a (Group II; P < 0.001) and rhIFNα-2a and vincristine combination (Group III; P < 0.001) decreased apoptosis. The results indicate that intratumoral rhIFNα-2a treatment alone is not effective in CTVT. However, combination of rhIFNα-2a and vincristine shortens the duration of treatment compared to vincristine therapy.

Neuroprotective activity of cannabinoid receptor-2 against oxidative stress and apoptosis in rat pups having experimentally-induced congenital hypothyroidism.

In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9, and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the three groups established comprised one male and two female rats, and they were coupled. Their pups were used. In the first two groups, the mothers were treated with 0.025% MMI during the critical period of the pregnancy. In the third group, as the control group, the mothers and pups were not treated. Euthanasia was applied to the pups in Group I on Day 10, and to the pups in Groups II and III on Day 21. In the biochemical analyses, total T4 levels of both mothers and pups in Group I and II were found to be lower than those of the control group. Histopathologically, karyopyknosis in migrating neurons and demyelinization were observed in both groups. Caspase-3 and -9 expressions and TUNEL reactions showed parallelism to these findings. eNOS and iNOS activities were also increased in Groups I and II. CB2 receptor activity was observed in the fore and mid brain in Group I, and in the whole brain in Group II. In conclusion, apoptosis was triggered via oxidative stress in hypothyroid pups. Accordingly, neuroprotective activity of CB2 receptors were motivated spontaneously to resist to CNS lesions during the first 3 weeks of postnatal period. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1334-1347, 2017.

How Sublethal Fenitrothion is Toxic in Carp (Cyprinus carpio L.) Fingerlings.

ABSTRACT The purpose of this study was to evaluate the effects of fenitrothion, an organophosphothionate insecticide, on selected serum hematological and biochemical parameters of carp (Cyprinus carpio L.) fingerlings and investigate histopathological changes after acute dose of exposure. Among those, cortisol and glucose are evaluated as responses of early life stages of carp to acute stress and hematological blood parameters are evaluated to investigate the mechanism of toxicity via histopathological changes to the standard test organism. No significant histological findings were observed in carp tissues (gills, liver, kidneys, spleen, gonads, brain, muscle, and skin) exposed to a sublethal concentration of 10 mg/L fenitrothion and controls. Hematocrit and erythrocyte counts were decreased significantly by exposure to fenitrothion when compared to the control group (25.26% +/- 0.82%, 1455 +/- 90.3 [10(3)/muL] vs. 28.83% +/- 1.60%, 1865 +/- 74.5 [10(3)/muL], P < 0.05), respectively. Leucocyte and thrombocyte counts did not change. Increases in plasma cortisol levels were found in the experimental group compared to controls (34.2 +/- 1.9 vs. 18.0 +/- 2.2, P < 0.05) respectively, while glucose, chloride, sodium, potassium, phosphorous, and brain MDA and FOX levels did not show significant differences from those of control (P > 0.05). As a result, we can conclude that early life stages of fish are very susceptible to the adverse effects of toxicants.