Expression of nectin-4 as a potential biomarker in enzootic nasal adenocarcinoma of goats.

The aim of this study was to test nectin-4 by immunohistochemistry as a potential biomarker in enzootic nasal adenocarcinoma (ENA) of goats. Twentyfour archival ENA case samples [from 14 male and 10 female hair goats (Capra hircus)] were used. The samples were stained with haematoxylin and eosin (HE). Nectin-4 expression was studied by immunohistochemistry. By microscopy, tubular, papillary, and mixed patterns of ENA were diagnosed in the cases. Immunohistochemically, the tumours showed moderate nectin-4 expression (++) in 14 cases (58.3%), strong expression (+++) in five cases (20.8%), and weak expression (+) in three cases (12.5%), while two cases (8.3%) were negative. Normal nasal tissues were not stained with nectin-4. The results suggest that nectin-4 may be used as a valuable biomarker of ENA.

LRP1 in GABAergic neurons is a key link between obesity and memory function.

OBJECTIVE: Low-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood-brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric acid (GABA)ergic neurons causes severe obesity in mice. However, the impact of LRP1 in inhibitory neurons on memory function and cognition in the context of obesity is poorly understood. METHODS: Mice lacking LRP1 in GABAergic neurons (Vgat-Cre; LRP1loxP/loxP) underwent behavioral tests for locomotor activity and motor coordination, short/long-term and spatial memory, and fear learning/memory. This study evaluated the relationships between behavior and metabolic risk factors and followed the mice at 16 and 32 weeks of age. RESULTS: Deletion of LRP1 in GABAergic neurons caused a significant impairment in memory function in 32-week-old mice. In the spatial Y-maze test, Vgat-Cre; LRP1loxP/loxP mice exhibited decreased travel distance and duration in the novel arm compared with controls (LRP1loxP/loxP mice). In addition, GABAergic neuron-specific LRP1-deficient mice showed a diminished capacity for performing learning and memory tasks during the water T-maze test. Moreover, reduced freezing time was observed in these mice during the contextual and cued fear conditioning tests. These effects were accompanied by increased neuronal necrosis and satellitosis in the hippocampus. Importantly, the distance and duration in the novel arm, as well as the performance of the reversal water T-maze test, negatively correlated with metabolic risk parameters, including body weight, serum leptin, insulin, and apolipoprotein J. However, in 16-week-old Vgat-Cre; LRP1loxP/loxP mice, there were no differences in the behavioral tests or correlations between metabolic parameters and cognition. CONCLUSIONS: Our findings demonstrate that LRP1 from GABAergic neurons is important in regulating normal learning and memory. Metabolically, obesity caused by GABAergic LRP1 deletion negatively regulates memory and cognitive function in an age-dependent manner. Thus, LRP1 in GABAergic neurons may play a crucial role in maintaining normal excitatory/inhibitory balance, impacting memory function, and reinforcing the potential importance of LRP1 in neural system integrity.

LRP1 mediates leptin transport by coupling with the short-form leptin receptor in the choroid plexus.

Adipocyte-derived leptin enters the brain to exert its anorexigenic action, yet its transport mechanism is poorly understood. Here we report that LRP1 (low-density lipoprotein receptor-related protein-1) mediates the transport of leptin across the blood-CSF barrier in Foxj1 expressing cells highly enriched at the choroid plexus (ChP), coupled with the short-form leptin receptor, and LRP1 deletion from ependymocytes and ChP cells leads to leptin resistance and hyperphagia, causing obesity. Thus, LRP1 in epithelial cells is a principal regulator of leptin transport in the brain.

An immunohistochemical study in cases with usual and unusual clinicopathological findings of canine visceral leishmaniosis.

The present study describes pathologic findings and immunohistochemical diagnosis of canine visceral leishmaniasis (CVL) in 22 dogs who died naturally in the Aegean region of Turkey. At necropsy, lymphadenomegaly, hepatosplenomegaly, hepatic, and nephrosclerotic lesions were conspicuous. Histopathologically, chronic inflammatory reactions of the spleen, lymph nodes, bone marrow, liver, and skin were marked findings. Cytological and histological examinations showed macrophages loaded with Leishmania amastigotes in these organs. Immunohistochemistry revealed that immunolabeling of amastigotes and/or parasite antigen, especially in the lymph nodes, spleen, bone marrow, liver, and skin, and occasionally, in the kidneys, intestines and lungs. Our laboratory results showed that immunohistochemistry should be included, along with cytological and histological examinations, in the diagnosis of CVL.

Corneal papilloma associated with papillomavirus in a one-humped camel (Camelus dromedarius).

A 15-year-old male dromedary camel with a history of chronic severe keratoconjunctivitis and corneal mass in the left eye of 6 months' duration was referred to the Veterinary Medical Teaching Hospital at Adnan Menderes University. A superficial keratectomy was performed and biopsy material submitted for histopathology. The diagnosis was corneal papilloma. There has been no recurrence of the neoplasm to date (6 months, 1 year). Corneal papilloma has not been reported previously in camels and seems to be associated with papillomavirus.

Antenatal pentoxifylline therapy to prevent endotoxin-induced fetal injury in the preterm goat model.

OBJECTIVE: Pentoxifylline (PTX) has immunomodulatory properties and is known to reduce sepsis-associated infant mortality. We aimed to evaluate maternal oral and intra-amniotic administration of PTX for the prevention of fetal inflammation and injury in a caprine model. MATERIALS AND METHODS: Inflammation-mediated fetal injury was induced with maternal granulocyte-colony stimulating factor and intra-amniotic endotoxin at 0.76 of gestation in date-mated pregnant goats. Eight groups were formed (n=4 each): Control, fetal injury, oral 30 mg/kg/day and 60 mg/kg/day PTX for 15 days + fetal injury, intra-amniotic 400 mg/kg and 800 mg/kg estimated fetal weight single-dose PTX with and without fetal injury. Preterm delivery by hysterotomy was performed at 0.80 of gestation to evaluate the fetal and placental effects. Immunochemistry for various markers including interleukins, caspases, cyclooxygenases, vimentin, myelin basic protein, and surfactant proteins were carried out in the fetal lungs, fetal brain, and placenta. Fetal plasma and amniotic fluid interleukins were also evaluated. Kruskal-Wallis H test and Mann-Whitney U test were used for comparisons. RESULTS: High-dose (60 mg/kg/day) maternal prophylactic oral treatment attenuated endotoxin-related histological injury and was related to low inflammatory marker expressions comparable to the controls (p>0.05 except cyclooxygenase 2). Following maternal oral administration, fetal plasma and amniotic fluid levels of the studied interleukins were also lower than the untreated endotoxin-exposed animals (p<0.05 for all comparisons). Intra-amniotic PTX was associated with inconsistent results and increased inflammatory markers in some fetuses. CONCLUSION: Oral PTX before preterm birth mitigates intrauterine inflammation with neuroprotective effects in the fetus. PTX can be considered as a candidate drug for fetal brain injury prevention in the preterm period.

Inflammation-mediated fetal injury by maternal granulocyte-colony stimulating factor and high-dose intraamniotic endotoxin in the caprine model.

OBJECTIVE: To define a novel experimental model with maternal intravenous (i.v.) granulocyte-colony stimulating factor (G-CSF) followed by a single- and high-dose of 20 mg intra-amniotic (IA) endotoxin to induce fetal brain injury in the preterm fetal goat. MATERIALS AND METHODS: Pregnant goats (n=4) were given 50 microg/day G-CSF into the maternal jugular vein through gestational days 110-115 (term, 150 days). At gestational day 115, 20 mg of IA endotoxin was administered. Following preterm delivery at day 120 by cesarean section umbilical cord, fetal lung and brain tissues were harvested for histopathology, immunohistochemistry, and electron microscopy. Inflammatory markers were evaluated in the amniotic fluid and fetal plasma. RESULTS: Necrotizing funisitis with abundant leukocyte infiltration and fetal brain injury was induced in all the fetuses in the experimental group. CONCLUSION: Maternal i.v. G-CSF for 5 days followed by 20 mg of IA endotoxin is a feasible caprine model to exacerbate intrauterine inflammation.

First case report of enzootic nasal adenocarcinoma in "Ouled Djellal" ewe in Algeria.

We report clinical and pathological features of enzootic nasal adenocarcinoma (ENA) in one sheep in Algeria. A one-year-old Ouled Djellal sheep from a large herd (~1240 animals), located in Bordj Bou Arreridj, Algeria, was clinically diagnosed by the presence of persistent seromucous nasal discharge, head shaking, muzzle licking, dyspnoea, exophthalmia and frontal protrusion. The sheep was euthanized, and the necropsy was performed. Gross examination showed soft touch, pinkish-white tumour masses in the nasal cavities with distortion of the turbinates and of the medium septum. According to clinical and pathological findings, the tumour has been defined as a low grade mixed nasal adenocarcinoma, with the presence of tubular and papillary structures. This is, to our knowledge, the first report of ENA in Algeria known to be associated with enzootic nasal tumour virus (ENTV) infection. However, such association requires confirmation by direct and/or indirect viral investigation.

Application of gaseous ozone for inactivation of Bacillus subtilis spores.

The effectiveness of gaseous ozone (O3) as a disinfectant was tested on Bacillus subtilis spores, which share the same physiological characteristics as Bacillus anthracis spores that cause the anthrax disease. Spores dried on surfaces of different carrier material were exposed to O3 gas in the range of 500-5000 ppm and at relative humidity (RH) of 70-95%. Gaseous O3 was found to be very effective against the B. subtilis spores, and at O3 concentrations as low as 3 mg/L (1500 ppm), approximately 3-log inactivation was obtained within 4 hr of exposure. The inactivation curves consisted of a short lag phase followed by an exponential decrease in the number of surviving spores. Prehydration of the bacterial spores has eliminated the initial lag phase. The inactivation rate increased with increasing O3 concentration but not >3 mg/L. The inactivation rate also increased with increase in RH. Different survival curves were obtained for various surfaces used to carry spores. Inactivation rates of spores on glass, a vinyl floor tile, and office paper were nearly the same. Whereas cut pile carpet and hardwood flooring surfaces resulted in much lower inactivation rates, another type of carpet (loop pile) showed significant enhancement in the inactivation of the spores.

Effects of Caffeine and Lycopene in Experimentally Induced Diabetes Mellitus.

OBJECTIVES: Diabetes mellitus (DM) is a global epidemic with increasing prevalence. The disease is chronic in nature, and patients must use antidiabetic drugs or insulin during their lifespan. Because of the difficulty of using injectable insulin preparations, patients and practitioners prefer to use oral antidiabetic drugs for prophylaxis and treatment. There are, however, numerous adverse effects of antidiabetic drugs and rapidly increasing attention is being paid to new nutraceutical drugs with fewer adverse effects. The purpose of this study was to evaluate the effects of caffeine and lycopene on streptozotocin (STZ)-induced DM in rats. METHODS: Caffeine and lycopene were administered to the study groups by oral gavages for 1 month whereafter experimental diabetes was induced in 90 rats in 6 groups. RESULTS: There were no pathological effects of lycopene and caffeine on the pancreas. Marked vacuolization and degeneration were observed in STZ-treated groups. Caffeine and lycopene decreased the pathological findings and lowered the blood and urine glucose levels in the rats with STZ-induced DM, whereas these compounds increased serum insulin levels. CONCLUSIONS: This study showed that caffeine and lycopene provided protective effects against experimentally induced DM. The protective effects of lycopene were observed to be much greater than those of caffeine.

Immunohistochemical expression of caspase-3, caspase-5, caspase-7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats exposed to zoledronic acid (ZOL) and basic fibroblast growth factor (bFGF).

BACKGROUND: Bisphosphonates (BPs) like zoledronic acid (ZOL) are widely used for the treatment of different diseases such as osteoporosis, metastatic bone diseases and hypercalcaemia. However, the effects of BPs on apoptosis of the liver and kidney after treatment are unclear. Furthermore, basic fibroblast growth factor (bFGF) is an angiogenic molecule, which plays an important role in angiogenesis and tissue repair. The present study investigated the expression of caspase-3, -5, -7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats treated with ZOL and bFGF. OBJECTIVE: The present study investigated the expression of caspase-3, -5, -7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats treated with ZOL and bFGF. ANIMALS AND METHODS: An animal model with 32 male Sprague Dawley rats was used. The effects of ZOL and bFGF on liver and kidney with the expressions of different apoptosis markers were studied histopathologically and immunohistochemically. Data were analyzed using Cronbach's alpha, Kruskal-Wallis and Bonnferroni-Dunn tests. RESULTS: The main microscopic findings were mononuclear cell infiltrations around the bile ducts, binuclear and markedly enlarged hepatocytes (cytomegaly) and mitotic figures in the liver of rats treated with ZOL only. Immunohistochemically, both APAF-1 and caspase-3, -5 and -7 expressions were found elevated significantly (P < 0.05) in the liver and kidney of these rats. CONCLUSIONS: Our findings showed that ZOL treatment increased while bFGF treatment decreased apoptosis significantly in the liver and kidney of Sprague Dawley rats. CLINICAL IMPORTANCE: The addition of bFGF to ZOL treatment of various diseases might reduce the ZOL effects.