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Microplastic pollution is an extremely emerging problem and its potential threats to the aquatic organisms were investigated worldwide. In this study, four different commercial fish species (Mullus barbatus (Linnaeus, 1758), Mullus surmuletus (Linnaeus, 1758), Mugil cephalus (Linnaeus, 1758), Saurida undosquamis (Richardson, 1848)) were used as a bioindicator to assess the microplastic pollution in the northeastern Mediterranean. The frequency of occurrence in the gastrointestinal tract (GIT) and gill was varied between 66-100% and 68-90%, respectively. The highest microplastic abundance was detected at the GIT of M. cephalus sampled from Asi River estuary. The majority of extracted microplastics were fiber, black in color and less than 1 mm in size. Fourier Transform Infrared Spectroscopy (FTIR) indicated the most common polymer type as polyethylene. This study is the first study examining the microplastic existence in gill and results obtained in this study improve the knowledge about the relationship of microplastic ingestion in fish and environmental conditions in the Northeastern Mediterranean Sea.

Introduction: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. Objective: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. Methods: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15 mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days. Cisplatin + gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day. A control group received 1 mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. Results: In cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin + gallic acid group, this biochemical, histopathological and functional changes were reversed. Conclusion: In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses. Resumo: Introdução: A cisplatina é um agente antineoplásico amplamente usado no tratamento de vários tipos de câncer. A ototoxicidade é um dos principais efeitos colaterais que restringem o uso da cisplatina. Objetivo: O objetivo deste estudo foi investigar a eficácia protetora do ácido gálico, em termos bioquímicos, funcionais e histopatológicos, contra a ototoxicidade induzida por cisplatina. Método: Vinte e oito ratas Sprague-Dawley foram incluídas. As ratas foram distribuídas aleatoriamente em quatro grupos de sete animais cada. O grupo cisplatina recebeu uma única dose intraperitoneal de 15 mg/kg de cisplatina. O grupo ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos. O grupo cisplatina + ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos e uma única dose intraperitoneal de 15 mg/kg de cisplatina no terceiro dia. O grupo controle recebeu 1 mL de solução salina via intraperitoneal por cinco dias consecutivos. Antes da administração do fármaco, todos os ratos foram expostos ao teste de emissões otoacústicas - produto de distorção. O teste foi repetido no sexto dia do estudo. Todos os ratos foram então sacrificados; as cócleas foram removidas e reservadas para análises bioquímicas e histopatológicas. Resultados: No grupo cisplatina, os valores da relação sinal-ruído do dia 6 foram significativamente mais baixos aos dos outros grupos. Além disso, os níveis de malondialdeído nos tecidos cocleares foram significativamente mais altos, e as atividades de superóxido dismutase e glutatione peroxidase foram significativamente mais baixas em comparação com o grupo controle. A avaliação histopatológica revelou erosão na estria vascular, degeneração e edema na camada de tecido conjuntivo em células endoteliais, comprometimento das células ciliadas externas e diminuição do número dessas células. No grupo cisplatina + ácido gálico, estas alterações bioquímicas, histopatológicas e funcionais foram revertidas. Conclusão: Tendo em vista os nossos achados, consideramos que o ácido gálico pode ter desempenhado um papel protetor contra a ototoxicidade induzida por cisplatina em ratas, conforme indicado pelos resultados do teste emissões otoacústicas - produto de distorção, achados bioquímicos e análises imuno-histoquímicas. Keywords: Cisplatin-induced ototoxicity, Gallic acid, Oxidative stress, DPOAE, Palavras-chave: Ototoxicidade induzida por cisplatina, Ácido gálico, Estresse oxidativo, EOAPD

Toxoplasma gondii is an important foodborne pathogen worldwide, with undercooked meat as the main source of human transmission. In this study, we determined the seroprevalence of T. gondii in free-range pigs from two adjacent villages in the Tumbes region of northern Peru, El Tutumo and Nuevo Progreso. We randomly selected 100 pig serum samples collected during a prior study and processed these using Western Blot to detect IgG anti-T. gondii antibodies. Results indicated a prevalence of 32% (32/100) to T. gondii in pigs. Free-ranging pigs from northern Peru represent a substantial risk for transmission of T. gondii to humans.

15-lipoxygenase-1 (15-LOX-1) oxygenates linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). The enzyme is widely suppressed in different cancers and its re-expression has tumor suppressive effects. 15-LOX-1 has been shown to inhibit neoangiogenesis in colorectal cancer (CRC); in the present study we confirm this phenomenon and describe the mechanistic basis. We show that re-expression of 15-LOX-1 in CRC cell lines resulted in decreased transcriptional activity of HIF1α and reduced the expression and secretion of VEGF in both normoxic and hypoxic conditions. Conditioned medium (CM) was obtained from CRC or prostate cancer cell lines re-expressing 15-LOX-1 (15-LOX-1CM). 15-LOX-1CM treated aortic rings from 6-week old C57BL/6 mice showed significantly less vessel sprouting and more organized structure of vascular network. Human umbilical vein endothelial cells (HUVECs) incubated with 15-LOX-1CM showed reduced motility, enhanced expression of intercellular cell adhesion molecule (ICAM-1) and reduced tube formation but no change in proliferation or cell-cycle distribution. HUVECs incubated with 13(S)-HODE partially phenocopied the effects of 15-LOX-1CM, i.e., showed reduced motility and enhanced expression of ICAM-1, but did not reduce tube formation, implying the importance of additional factors. Therefore, a Proteome Profiler Angiogenesis Array was carried out, which showed that Thrombospondin-1 (TSP-1), a matrix glycoprotein known to strongly inhibit neovascularization, was expressed significantly more in HUVECs incubated with 15-LOX-1CM. TSP-1 blockage in HUVECs reduced the expression of ICAM-1 and enhanced cell motility, thereby providing a mechanism for reduced angiogenesis. The anti-angiogenic effects of 15-LOX-1 through enhanced expressions of ICAM-1 and TSP-1 are novel findings and should be explored further to develop therapeutic options.

The zebrafish has become a popular model for studying normal brain aging due to its large fecundity, conserved genome, and available genetic tools; but little data exists about neurobiological age-related alterations. The current study tested the hypothesis of an association between brain aging and synaptic protein loss across males and females. Western blot analysis of synaptophysin (SYP), a presynaptic vesicle protein, and postsynaptic density-95 (PSD-95) and gephyrin (GEP), excitatory and inhibitory postsynaptic receptor-clustering proteins, respectively, was performed in young, middle-aged, and old male and female zebrafish (Danio rerio) brains. Univariate and multivariate analyses demonstrated that PSD-95 significantly increased in aged females and SYP significantly decreased in males, but GEP was stable. Thus, these key synaptic proteins vary across age in a sexually dimorphic manner, which has been observed in other species, and these consequences may represent selective vulnerabilities for aged males and females. These data expand our knowledge of normal aging in zebrafish, as well as further establish this model as an appropriate one for examining human brain aging.

Dietary ion content is known to alter the acid-base balance in freshwater fish. The current study investigated the metabolic impact of acid-base disturbances produced by differences in dietary electrolyte balance (DEB) in the meagre (Argyrosomus regius), an euryhaline species. Changes in fish performance, gastric chyme characteristics, pH and ion concentrations in the bloodstream, digestive enzyme activities and metabolic rates were analyzed in meagre fed ad libitum two experimental diets (DEB 200 or DEB 700 mEq/kg) differing in the Na2CO3 content for 69 days. Fish fed the DEB 200 diet had 60–66% better growth performance than the DEB 700 group. Meagre consuming the DEB 200 diet were 90–96% more efficient than fish fed the DEB 700 diet at allocating energy from feed into somatic growth. The pH values in blood were significantly lower in the DEB 700 group 2 h after feeding when compared to DEB 200, indicating that acid-base balance in meagre was affected by electrolyte balance in diet. Osmolality, and Na+ and K+ concentrations in plasma did not vary with the dietary treatment. Gastric chyme in the DEB 700 group had higher pH values, dry matter, protein and energy contents, but lower lipid content than in the DEB 200 group. Twenty-four hours after feeding, amylase activity was higher in the gastrointestinal tract of DEB 700 group when compared to the DEB 200 group. DEB 700 group had lower routine metabolic (RMR) and standard metabolic (SMR) rates, indicating a decrease in maintenance energy expenditure 48 h after feeding the alkaline diet. The current study demonstrates that feeding meagre with an alkaline diet not only causes acid-base imbalance, but also negatively affects digestion and possibly nutrient assimilation, resulting in decreased growth performance. Fil: Magnoni, Leonardo Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina. Terminal de Cruzeiros do Porto de Leixões; Brasil Fil: Salas Leiton, Emilio. Terminal de Cruzeiros do Porto de Leixões; Brasil. IFAPA; España Fil: Peixoto, Maria João. Terminal de Cruzeiros do Porto de Leixões; Brasil. Universidad de Porto; Portugal Fil: Pereira, Luis. Terminal de Cruzeiros do Porto de Leixões; Brasil Fil: Silva Brito, Francisca. Terminal de Cruzeiros do Porto de Leixões; Brasil Fil: Fontinha, Filipa. Terminal de Cruzeiros do Porto de Leixões; Brasil Fil: Gonçalves, José F.M.. Terminal de Cruzeiros do Porto de Leixões; Brasil. Universidad de Porto; Portugal Fil: Wilson, Jonathan M.. Terminal de Cruzeiros do Porto de Leixões; Brasil. Universidad de Porto; Portugal. Wilfrid Laurier University; Canadá Fil: Schrama, Johan W.. University of Agriculture Wageningen; Países Bajos Fil: Ozório, Rodrigo O.A.. Terminal de Cruzeiros do Porto de Leixões; Brasil. Universidad de Porto; Portugal

This study tested the hypothesis that the hypothalamus participates in the decompensatory phase of hemorrhage by measuring Fos immunoreactivity and by inhibiting neuronal activity in selected hypothalamic nuclei with lidocaine or cobalt chloride. Previously, we reported that inactivation of the arcuate nucleus inhibited, but did not fully prevent, the fall in arterial pressure evoked by hypotensive hemorrhage. Here, we report that hemorrhage (2.2 ml/100 g body weight over 20 min) induced Fos expression in a high percentage of cells in the paraventricular, supraoptic and arcuate nuclei of the hypothalamus as shown previously. Lower densities of Fos immunoreactive cells were also found in the medial preoptic area (mPOA), anterior hypothalamus, lateral hypothalamus (LH), dorsomedial hypothalamus, ventromedial hypothalamus (VMH) and posterior hypothalamus. Bilateral injection of lidocaine (2%; 0.1 mu l or 0.3 mu l) or cobalt chloride (5 mM; 0.3 mu l) into the tuberal portion of the LH immediately before hemorrhage was initiated reduced the magnitude of hemorrhagic hypotension and bradycardia significantly. Lidocaine injection into the VMH also attenuated the fall in arterial pressure and heart rate evoked by hemorrhage although inactivation of the mPOA or rostral LH was ineffective. These findings indicate that hemorrhage activates neurons throughout much of the hypothalamus and that a relatively broad area of the hypothalamus, extending from the arcuate nucleus laterally through the caudal VMH and tuberal LH, plays an important role in the decompensatory phase of hemorrhage. Office of Naval Research - N00014-00-1-0056

Larval therapy is used as alternative treatment for hard-to-heal chronic and infected wounds. Lucilia sericata is the most used blowfly species. However, it has been shown recently that Sarconesiopsis magellanica larval excretions and secretions have potent antibacterial activity; this blowfly belongs to the Calliphoridae family.The present work has dealt with evaluating larval therapy using S. magellanica on wounds induced in diabetic rabbits and its action was compared to the effect induced by L. sericata. Twelve New Zealand White rabbits (. Oryctolagus cuniculus) were used; they were divided into 4 groups, the first two being treated with larval therapy derived from both aforementioned necrophagous blowflies, an antibiotic was used in the third and the fourth was used as control. All the animals were wounded on the back and infected with Pseudomonas aeruginosa and Staphylococcus aureus.Samples of the secretion from each animal's infected wound were taken and sown on blood agar. The colony forming units were then counted. The PUSH scale was used for the macroscopic evaluation of the wounds.Bacterial control was encountered 48. h post-treatment in the treatments involving larval therapy and to a lesser extent with the antibiotic. Likewise, wound debridement was quicker and more efficient with larval therapy compared to the antibiotic group; however, wound closing time was 23 days in all treatments. The group treated with S. magellanica larvae had relatively quicker evolution until the proliferation phase and the start of maturation, even though there were no significant differences between both blowfly species evaluated here regarding treatments by the end of the treatment period.The present study has validated the diabetic rabbit model for inducing chronic wounds regarding larval therapy and has likewise confirmed the effectiveness of S. magellanica-derived larval therapy as an alternative for curing and healing wounds. © 2015 Elsevier B.V.

ß-Amyloid (Aß) plaques in Alzheimer (AD) brains are surrounded by severe dendritic and axonal changes, including local spine loss, axonal swellings and distorted neurite trajectories. Whether and how plaques induce these neuropil abnormalities remains unknown. We tested the hypothesis that oligomeric assemblies of Aß, seen in the periphery of plaques, mediate the neurodegenerative phenotype of AD by triggering activation of the enzyme GSK-3ß, which in turn appears to inhibit a transcriptional program mediated by CREB. We detect increased activity of GSK-3ß after exposure to oligomeric Aß in neurons in culture, in the brain of double transgenic APP/tau mice and in AD brains. Activation of GSK-3ß, even in the absence of Aß, is sufficient to produce a phenocopy of Aß-induced dendritic spine loss in neurons in culture, while pharmacological inhibition of GSK-3ß prevents spine loss and increases expression of CREB-target genes like BDNF. Of note, in transgenic mice GSK-3ß inhibition ameliorated plaque-related neuritic changes and increased CREB-mediated gene expression. Moreover, GSK-3ß inhibition robustly decreased the oligomeric Aß load in the mouse brain. All these findings support the idea that GSK3ß is aberrantly activated by the presence of Aß, and contributes, at least in part, to the neuronal anatomical derangement associated with Aß plaques in AD brains and to Aß pathology itself. © 2011 Elsevier Inc.

In addition to their role in physiological activities, ionotropic glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) play an important role in neuronal death, especially that following ischemic insults. In this study, we examined the effect of single (SI) and twice repeated (RI)-4-vessel occlusion-ischemia on rat performance in the 8-armed radial maze test. Moreover, the effects of SI and RI on the AMPARs subunits glutamate receptor (GluR) 1 and GluR2 flip and flop variants composition in the CA1 subregion of the hippocampus were investigated using RT-PCR, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and expressed as their ratios to the latter. The results showed that SI and RI impaired the maze performance by decreasing correct choices and increasing the error choices, but RI increased error choices to a greater extent than the SI. The SI reduced only GluR1 flip/GAPDH on day 1. The SI did not alter ratios of GluR2 variants to those of GluR1. On the other hand, the RI decreased GluR2 flip and flop variants after 1 and 3 days, respectively, whereas after 7 days, it increased the flip variant of both GluR1 and GluR2. Moreover, the RI reduced ratios of GluR2 variants to those of GluR1. These results reveal the differential effects of the SI and RI on memory and expression of the AMPARs subunits GluR1 and GluR2 and their flip and flop variants in the CA1. Keywords:: AMPA GluR1 GluR2 flip and flop, hippocampus CA1, single- and repeated-ischemia, memory, Alzheimer’s disease

We aimed to investigate the effects of grape seed extract (GSE) and vitamin E (Vit E) on oxidative stress and apoptosis in the hippocampus of streptozotocin-induced diabetic rats. In Control, Diabetic, and Diabetic treated with GSE (Diabetic + GSE) and vitamin E (Diabetic + Vit E) groups, oxidative stress index (OSI), TUNEL staining and Bcl-2, Bcl-XL, Bax, caspase-3, -9, and -8, Cyt-c, TNF-alpha, and NF-kappa B gene expressions were evaluated. OSI was significantly increased in the plasma and hippocampus of the Diabetic compared to Control group and decreased in Diabetic + GSE and Diabetic + Vit E groups compared to Diabetic. TUNEL positive neurons significantly increased in the hippocampus of the Diabetic group compared to Control and decreased in Diabetic + GSE (more prominently) and Diabetic + Vit E groups compared to Diabetic. In the hippocampus of the Diabetic group, Bcl-2 and Bcl-XL gene expressions were significantly decreased; Bax, caspase-3, -9, and -8, Cyt-c, TNF-alpha, and NF-kappa B gene expressions were significantly increased compared to Control. In Diabetic + GSE and Diabetic + Vit E groups, Bcl-2 gene expressions were significantly increased; Bcl-XL gene expressions did not differ compared to the Diabetic group. The expression of Bax, caspase-3, -9, and -8, Cyt-c, TNF-alpha, and NF-kappa B genes in the Diabetic + GSE group and the expression of caspase-3 and -9, TNF-alpha, and NF-kappa B genes in the Diabetic + Vit E group were significantly decreased compared to Diabetic. In conclusion, GSE (more prominently) and vitamin E decreased oxidative stress and neuronal apoptosis occurring in the hippocampus of diabetic rats. (C) 2014 Elsevier B.V. All rights reserved.

Objective: Apoptosis is the early and predominant form of cell death in infarcted myocardia. The aim of the study was to investigate the effects of trimetazidine (TMZ) and N-acetylcysteine (NAC), used alone or in combination, on oxidative stress, infarct size, and ischemia-reperfusion (IR)-induced cardiomyocyte apoptosis in a rat model of myocardial IR. Methods and results: Myocardial IR was established by ligating an area under the left main coronary artery for 30 min followed by 3 h of reperfusion. Saline (1 ml/kg), NAC (50, 150 mg/kg), or TMZ (3, 5 mg/kg) was intravenously injected during the middle of the ischemic period. At the end of the reperfusion, blood samples were collected from the animals to measure serum M30 and M65 levels, which are markers of cell death, the S100b level, which is a marker of inflammation, and the malondialdehyde (MDA) level, which is a marker of oxidative stress. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by caspase-3 immunostaining and a TUNEL assay. TMZ and NAC, either alone or in combination, significantly reduced serum MDA levels, infarct area and apoptotic activity compared to those observed in saline group. Interestingly, the infarct area was more smaller in TMZ (3 and 5 mg/kg) injected groups (9.72 +/- 1.3% and 9.96 +/- 2.3%) than those observed in NAC (50 and 150 mg/kg) (16.1 +/- 2.5% and 19.1 +/- 2.14%) or TMZ (5 mg/kg)- NAC (150 mg/kg) combination groups (16.9 +/- 1.6%). However, the apoptotic activity was reduced more significantly in the combination of TMZ (5 mg/kg)-NAC (50 mg/kg) compared to TMZ-only group. Neither TMZ or NAC treatments nor the combination of the drugs significantly affected serum M30, M65 and S100B levels. Conclusion: Intravenous NAC and TMZ administration decreased oxidative stress, infarct area and apoptotic activity in a rat model of IR. Although the combination treatment was more effective in reducing the apoptotic activity than either treatment groups alone, TMZ treatment was more successful in reducing the infarct area than NAC or combination treatments. Present results suggest that, in addition to mechanical attempts to secure myocardial reperfusion, the use of TMZ and NAC may help to reduce IR injury.

Obese obob mice with strong overexpression of the human apolipoprotein C1 (APOC1) exhibit excessive free fatty acid (FFA) and triglyceride (TG) levels and severely reduced body weight (due to the absence of subcutaneous adipose tissue) and skin abnormalities. To evaluate the effects of APOC1 overexpression on hepatic and peripheral insulin sensitivity in a less-extreme model, we generated obob mice with mild overexpression of APOC1 (obob/APOC1+/-) and performed hyperinsulinemic clamp analysis. Compared with obob littermates, obob/APOC1+/- mice showed reduced body weight (-25%) and increased plasma levels of TG (+632%), total cholesterol (+134%), FFA (+65%), glucose (+73%, and insulin (+49%). Hyperinsulinemic clamp analysis revealed severe whole-body and hepatic insulin resistance in obob/APOC1+/- mice and, in addition, increased hepatic uptake of FFA and hepatic TG content. Treatment of obob/APOC1+/- mice with rosiglitazone strongly improved whole-body insulin sensitivity as well as hepatic insulin sensitivity, despite a further increase of hepatic fatty acid (FA) uptake and a panlobular increase of hepatic TG accumulation. We conclude that overexpression of APOC1 prevents rosiglitazone-induced peripheral FA uptake leading to severe hepatic steatosis. Interestingly, despite rosiglitazone-induced hepatic steatosis, hepatic insulin sensitivity improves dramatically. We hypothesize that the different hepatic fat accumulation and/or decrease in FA intermediates has a major effect on the insulin sensitivity of the liver. Chemicals / CAS: glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; rosiglitazone, 122320-73-4, 155141-29-0; Apolipoprotein C-I; Apolipoproteins C; Blood Glucose; Fatty Acids; Insulin, 11061-68-0

Background: To investigate the protective effect of 2-aminoethyl diphenylborinate (2-APB) against ischemia-reperfusion (I/R) injury in the rat kidney by an experimental study. Materials and methods: Thirty male Sprague-Dawley rats were randomly divided into the following three groups: (1) sham group, (2) I/R group, and (3) I/R + 2-APB group. Renal I/ R injury was induced by clamping the left renal pedicle for 45 min after right nephrectomy, followed by 3 h of reperfusion. The therapeutic agent 2-APB was administered intravenously at a dose of 2 mg/kg 10 min before renal ischemia. Glutathione, superoxide dismutase, total antioxidant capacity, malondialdehyde, tumor necrosis factor a, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were measured from blood samples, and the rats were sacrificed subsequently. Tissue samples were scored histopathologically. Visualization of apoptotic cells was performed using the terminal deoxynucleotidyl transferase dUTP nick end labeling staining method. Results: 2-APB significantly reduced serum malondialdehyde, tumor necrosis factor a, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels in the I/R injury group. However, glutathione, superoxide dismutase, and total antioxidant capacity levels increased significantly. Histopathologic scores were significantly better and the rate of apoptosis was lower in the 2-APB group. Conclusions: 2-APB reduces oxidative stress and damage caused by renal I/R injury. The results of this study demonstrate that 2-APB can be used as an effective agent against I/R injury in the kidney.

Background: Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in newborn infants but up to now there is no completely effective treatment for it. Objective: In order to show that a combination of melatonin and prostaglandins may be useful to save lives, we use newborn rat as a model of necrotizing enterocolitis to test the hypothesis of using the combination therapy might have more potential effect on mucosal cytoprotection and healing. Patients and methods: A total of 60 newborn pups from 5 time-mated Sprague-Dawley pregnant rats were divided equally into 5 groups as follows: NEC (subjected to NEC), NEC + Melatonin, NEC + Prostaglandin, NEC + Prostaglandin + Melatonin and control. These animals were fed with hyperosmolar formula 3 times daily and subjected to 100% CO2 inhalation for 10 min, +4 degrees C cold exposure for 5 min, and 97% O-2 for 5 min twice daily to induce NEC. This procedure was applied to the pups for 3 days. Results: The macroscopic scoring, intestinal injury scoring and apoptosis index scoring were all found to be significantly lower in NEC + Prostaglandin + Melatonin group compared with NEC group. Anti-oxidant enzyme activities were significantly higher, whereas lipid peroxidation was significantly lower in NEC + Prostaglandin + Melatonin group compared with NEC group. Conclusion: This combination therapy showed cytoprotective and healing effects on mucosa in the intestinal tissue of rat pups in necrotizing enterocolitis model. Therefore, this therapy might also show benefit in preterm infants with NEC. After confirmation of this data by other clinical and experimental studies, it may be a novel therapeutic option for the prevention of NEC in preterm infants.

Background: Oxygen-induced lung injury is believed to lead to the development of bronchopulmonary dysplasia in premature infants. We have evaluated the beneficial effects of Nigella sativa oil (NSO) on rats with hyperoxia-induced lung injury. Methods: Thirty newborn Sprague-Dawley rats were randomly divided into 3 groups as hyperoxia (95% O-2), hyperoxia + NSO and control (21% O-2). Pups in the hyperoxia + NSO group were administered intraperitoneal NSO at a dose of 4 ml/kg daily during the study period. Histopathologic, immunochemical, and biochemical evaluations (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malonaldehyde [MDA] and myeloperoxidase [MPO]) were performed. Results: In the histopathologic and immunochemical evaluation, severity of lung damage was significantly lower in the hyperoxia + NOS group (P

We report the distribution of immunoreactive cell bodies and fibers containing calcitonin gene-related peptide in the alpaca diencephalon. This study was carried out in alpacas that lived from birth to death at 0. m above sea level. Immunoreactive fibers were widely distributed throughout the thalamus and hypothalamus. A moderate density of these fibers was found in the zona incerta, the central medial, subparafascicular, reuniens and rhomboid thalamic nuclei, in the preoptic, anterior, lateral and dorsal hypothalamic areas, around the fornix, in the posterior, ventromedial and paraventricular hypothalamic nuclei and in the lateral mammillary nucleus. Cell bodies were only found in the hypothalamus: a high density in the paraventricular and supraoptic hypothalamic nuclei and a low density in the anterior, lateral and dorsal hypothalamic areas, around the fornix, and in the posterior and ventromedial hypothalamic nuclei. The widespread distribution of calcitonin gene-related peptide in the alpaca diencephalon suggests that it is involved in many physiological actions that must be investigated in-depth in the future, since alpacas lives from 0. m above sea level to altitudes of up to 5000. m altitude and hence the involvement of neuropeptides in special and unique regulatory physiological mechanisms could be suggested. .

Ethnopharmacological relevance Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) is widely used by populations living in South America to treat many ailments associated with inflammatory disorders. Mitraphylline was shown to be the major pentacyclic oxindolic alkaloid present in the bark chloroformic extract of this plant. Its activity against cytokines involved in inflammation process was tested in a murine model in vivo . Materials and methods Mice received mitraphylline once a day for 3 days at 30 mg/kg/day by oral route. Then, they were subjected to bacterial lipopolysaccharide (LPS) endotoxin (15 mg/kg) and the LPS-induced production of 16 different cytokines was determined by Elisa multiplex. Control group received dexamethasone orally at 2 mg/kg/day. Toxicity on K565 cells and murine peritoneal macrophages, in vitro , at doses up to 100 μM was monitored by XTT-colorimetric assay. Results and conclusions For the first time mitraphylline was tested in vivo against a large range of cytokines that play a crucial role in inflammation. Mitraphylline inhibited around 50% of the release of interleukins 1α, 1β, 17, and TNF-α. This activity was similar to dexamethasone. It also reduced almost 40% of the production of interleukin 4 (IL-4) while the corticoid did not. Lastly it did not show any toxicity on K565 cells nor murine macrophages at doses up to 100 μM.

Melittin is a polypeptide component of bee venom that leads to an increase in arachidonic acid release and subsequently in prostaglandin synthesis by activating phospholipase A 2 . Recently we demonstrated that centrally or peripherally administrated melittin caused pressor effect and central thromboxane A 2 (TXA 2 ) and cholinergic system mediated these effects of melittin. Also centrally injected histamine leads to pressor and bradycardic response by activating central histamine receptors in normotensive rats and central cholinergic system involved the effects of histamine. The present study demonstrates an involvement of the central histaminergic system in melittin-induced cardiovascular effect in normotensive rats. Experiments were carried out in male Sprague Dawley rats. Intracerebroventricularly (i.c.v.) injected melittin (0.5, 1 and 2nmol) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR) as we reported previously. Moreover, H 2 receptor antagonist ranitidine (50nmol; i.c.v.) almost completely and H 3 /H 4 receptor antagonist thioperamide (50nmol; i.c.v.) partly blocked melittin-evoked cardiovascular effects, whereas H 1 receptor blocker chlorpheniramine (50nmol; i.c.v.) had no effect. Also centrally injected melittin was accompanied by 28% increase in extracellular histamine concentration in the posterior hypothalamus, as shown in microdialysis studies. In conclusion, results show that centrally administered melittin causes pressor and bradycardic response in conscious rats. Moreover, according to our findings, there is an involvement of the central histaminergic system in melittin-induced cardiovascular effects.

No disease-specific neuronal antibodies have so far been defined in neuro-Behcet's disease (NBD). Immunohistochemistry and immunocytochemistry studies showed antibodies to hippocampal and cerebellar molecular layers and the surface antigens of cultured hippocampal neurons in sera and/or cerebrospinal fluids (CSF) of 13 of 20 NBD and 6 of 20 BD patients but not in multiple sclerosis or headache controls. Screening with a protein macroarray led to identification of stress-induced-phosphoprotein-1 (STIP-1) as an antigenic target. High-titer STIP-1-antibodies were detected in 6 NBD patients' sera but not in controls. These results suggest that neuronal antibodies could be useful as diagnostic biomarkers in NBD. (C) 2011 Elsevier B.V. All rights reserved.

[EN] Dielectric measurements of different standard solutions (nucleotides, nucleosides, lactic acid and myoglobin) were assayed simulating the concentrations of these substances in early postmortem meat. These assays were performed for considering the potential use of dielectric spectra for the quality control of meat. Good correlations among solutions of Adenosine Triphosphate (ATP), Inosine Monophosphate (IMP) and lactic acid with loss factor at punctual frequencies (0.5, 0.915 and 1 GHz) were found. The other assayed substances did not present a marked effect over the electromagnetic spectra. Good correlations of dielectric properties with IMP and lactic acid content of real pork meat samples were also found at 0.5 GHz. This work is presenting prospective data of dielectric spectra for certain key biochemical markers in order to consider its potential application as a non-destructive control sensor for the prediction of pork meat quality. (C) 2010 Elsevier Ltd. All rights reserved., Grant from Agroalimed (Conselleria de Agricultura, Pesca y Alimentacion, Valencia, Spain) and FPU grant to M.C. from Ministry of Science and Innovation (Madrid, Spain) are fully acknowledged. Work prepared within the Unidad Asociada IAD (UPV)-IATA (CSIC) framework.

The distribution of tyrosine hydroxylase (TH) in the brainstem of alpaca (Lama pacos) has been analysed using immunohistochemical methods. The following catecholaminergic cell nuclei have been detected: A1, C1, A2, C2 and area postrema in the medulla oblongata; A5, A6d, A7sc and A7d in the pons; as have several mesencephalic groups: A8, A9l, A9m, A9v, A9pc, A10, A10c, A10d and A10dc. This nuclear parcellation differs from that found in rodents, but agrees with the results reported in other members of the Artiodactyla order, such as giraffe or pig, and with the catecholaminergic distribution detected in species of other mammalian orders. Thus, these findings support the hypothesis that the animals included in the same order show the same nuclear complement in the neuromodulatory systems. In addition, it seems that other species share the same catecholaminergic groups as the alpaca, suggesting that a specific nuclear disposition was important and worth maintaining throughout evolution. Moreover, the distribution of TH has been compared with that of CGRP by double immunohistochemistry. Double-labelled neurons were very isolated and observed only in a few catecholaminergic groups: A1 and C2 in the medulla oblongata, A6d, A7sc and A7d in the pons, and A9l in the mesencephalon. However, interaction between TH and CGRP may be possible in more brainstem regions, particularly the area postrema. This interaction may prove important in the regulation of the specific cardiovascular control of alpacas given their morphological characteristics.

The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operate 1; Group 2, saline; Group 3, citicoline (400 mg/kg intraperitoneal.); Group 4, hypothermia (34 +/- 1 degrees C); Group 5, citicoline + hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical (mean standard deviation, 0.71 +/- 0.75) was lower compared to Groups 3, 4 and 5 (2.33 +/- 0.81; 3.00 +/- 0.00; 2.20 +/- 0.83; p < 0.05). There was higher expression of cispase-3 proteins in Group 2 (2.28 +/- 0.95) compared to Group 5 (1.50 +/- 0.83; p < 0.05). Bax proteins were also increased in Group 2 (1.85 +/- 1.06) compared to Group 5 (0.40 +/- 0.54) and in Group 4 (2.00 +/- 0.00) compared to Group 5 (0.40 +/- 0.54; p < 0.05). Significant differences in caspase-9 immunostaining scores were found in Group 2 (2.29 +/- 0.96) compared to Group 5 (0.20 +/- 0.44) (p < 0.05); Group 3 (1.00 +/- 0.70) compared to Group 5 (0.20 +/- 0.44: p, < 0.05); and Group 4 (3.00 +/- 0.00; p < 0.05) compared to Group 5 (0.40 +/- 0.54; p < 0.05). Thus by suppressing apoptotic processes citicoline with hypothermia is more effective than ;either used alone in ameliorating cerebral damage after transient focal ischemia. (C) 2009 Elsevier Ltd. All rights reserved.

Dogan Ekici, Asiye Isin/0000-0003-4062-9519; Ozkan, Ferda/0000-0002-9919-0582 WOS: 000255339000014 PubMed: 18342510 The human brain is uniquely powerful in its cognitive abilities, yet the hippocampal and neocortical circuits that mediate these complex functions are highly vulnerable during aging. In this study, we analyzed age-related changes in the rat hippocampus by studying newborn (1 month), middle-aged (12 months), and older (24 months) male and female Sprague-Dawley rats. We evaluated neuronal dystrophy, neuron scattering, and granulovacuolar degeneration in the hippocampal area using light microscopy, according to age and gender. We detected significant neuronal dystrophy in the CA1, CA2, and CA3 areas in male rats, and in the CA1, CA3, and CA4 areas in female rats. Degenerative changes, indicated by neuron scattering, were observed in the CA1, CA2, and CA3 areas of male and the CA2 and CA4 areas of female rats. Changes in all areas of the hippocampus were observed with increasing age; these changes included neuronal dystrophy and neuron scattering and did not differ significantly between male and female rats. (C) 2007 Elsevier Ltd. All rights reserved.

Severe blood loss lowers arterial pressure through a central mechanism that is thought to include opioid neurons. In this study, we investigated whether hemorrhage activates proopiomelanocortin (POMC) neurons by measuring Fos immunoreactivity and POMC mRNA levels in the medial basal hypothalamus. Hemorrhage (2.2 ml/100 g body weight over 20 min) increased the number of Fos immunoreactive neurons throughout the rostral-caudal extent of the arcuate nucleus, the retrochiasmatic area and the peri-arcuate region lateral to the arcuate nucleus where POMC neurons are located. Double label immunohistochemistry revealed that hemorrhage increased Fos expression by beta-endorphin immunoreactive neurons significantly. The proportion of beta-endorphin immunoreactive neurons that expressed Fos immunoreactivity increased approximately four-fold, from 11.7 +/- 1.4% in sham-operated control animals to 42.0 +/- 5.2% in hemorrhaged animals. Hemorrhage also increased POMC mRNA levels in the medial basal hypothalamus significantly, consistent with the hypothesis that blood loss activates POMC neurons. To test whether activation of arcuate neurons contributes to the fall in arterial pressure evoked by hemorrhage, we inhibited neuronal activity in the caudal arcuate nucleus by microinjecting the local anesthetic lidocaine (2%; 0.1 or 0.3 mu l) bilaterally 2 min before hemorrhage was initiated. Lidocaine injection inhibited hemorrhagic hypotension and bradycardia significantly although it did not influence arterial pressure or heart rate in non-hemorrhaged rats. These results demonstrate that hemorrhage activates POMC neurons and provide evidence that activation of neurons in the arcuate nucleus plays an important role in the hemodynamic response to hemorrhage.

In this study, we aimed to investigate the effect of vitamin A on the transformation of the Ito cells to fibrogenic form and suppression of the development of fibrosis. Carbon tetrachloride intoxication was performed on rats for 2, 8, 12 or 20 weeks and 5 x 10(4) IU vitamin A (as retinol palmitate) was injected subcutaneously once every 4 weeks. Ito cells were detected by gold chloride impregnation, as well as desmin and alpha-smooth muscle actin (alpha-SMA) immunohistochemistry. Additionally, all groups were examined ultrastructurally. The number of Ito cells that were labelled positively with gold impregnation decreased in the fibrotic groups; however, alpha-SMA and desmin immunopositive Ito cells increased. The samples from animals that were treated with vitamin A showed an increase in labelling with gold impregnation but a decrease in alpha-SMA immunopositivity. The data showed that vitamin A can prevent hepatic injury, by suppressing the transformation of Ito cells to fibrogenic form. We conclude that vitamin A has potential for the treatment of hepatic fibrotic diseases. alpha-SMA immunohistochemistry was found to be more informative than desmin immunohistochemistry for monitoring Liver fibrosis.

Background: Numerous experimental and clinical studies have shown that intrastriatal fetal mesencephalic grafts grow, survive, and reinnervate host brain tissue, resulting in partial recovery of motor deficits. In addition, pharmacological evidence indicates that these grafts increase dopamine secretion in lesioned brain. However, to date, no grafting method has completely restored the nigrostriatal pathway, and there is no consensus on optimal graft numbers or locations. This study compared outcomes with multiple striatal grafts vs a single intranigral graft in a rat model of Parkinson disease. Methods: Forty-one female Wistar rats weighing 200 to 250 g were used. First, baseline rotational behavior testing with amphetamine injection was done to identify each animal's dominant nigrostriatal pathway (left vs right hemisphere). Some rats then received a unilateral intranigral injection of 6-hydroxydopamine (4 mu L [8 mu g]) to produce the Parkinson model lesion, and rotational testing was repeated. One group of the lesioned rats received a single intranigral injection of suspended fetal ventral mesencephalic cells (n = 11), and another received multiple intrastriatal grafts of the same type (n = 11). Results: Both grafted groups showed significant improvement on rotational testing with amphetamine and apomorphine at 6 weeks "postgrafting" (P

This study tested the hypothesis that the ventrolateral column of the midbrain periaqueductal gray (vlPAG) region mediates the hypotension and bradycardia evoked by visceral nociception. To test this, the local anesthetic lidocaine (2%; 0.5 microl) was microinjected into the vlPAG of halothane-anesthetized rats bilaterally and visceral nociception was induced 2 min later by injecting 5% acetic acid (0.5 ml) intraperitoneally. Acetic acid injection caused an abrupt fall in arterial pressure (-12.2+/-2.1 mm Hg) and heart rate (-37+/-93 bpm) lasting approximately 15 min. Lidocaine injection into the vlPAG prevented the fall in arterial pressure and heart rate completely. Cobalt chloride (5 mM; 0.2 or 0.5 microl) injection into the vlPAG also prevented nociceptive hypotension but it did not affect the fall in heart rate significantly. Lidocaine pretreatment also inhibited the depressor response caused by intramuscular formalin (5%; 0.2 ml) administration, a model of deep somatic nociception, although it did not prevent the response completely. To determine if opioid receptors mediate the response, selective mu, delta or kappa opioid receptor antagonists were microinjected into the vlPAG 5 min before intraperitoneal (ip) acetic acid administration. Naltrindole, a delta receptor antagonist, inhibited the response significantly but mu and kappa antagonists were completely ineffective. Lidocaine and naltrindole had no effect when injected into the dorsolateral PAG and did not influence cardiovascular function when injected into the vlPAG of saline treated control animals. These data support the hypothesis that the vlPAG mediates the depressor response evoked by visceral nociception and indicate that delta opioid receptors participate in the response.

The spatial memory impairment and expression of apoptotic cells in hippocampal CA1 cells were investigated in rats using single and repeated ischemia models. The neuroprotective and memory-improving effect of YM-90K, an ?-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, was compared to MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. Twice-repeated ischemia, but not single ischemia, impaired the spatial memory and increased expression of apoptotic cells. YM-90K, given before and 6 h after the second reperfusion, significantly improved the memory and reduced the apoptotic cells 7 days after the second reperfusion in repeated ischemia. MK-801 neither improved the spatial memory nor reduced apoptotic cells. The present study showed that delayed expression of apoptotic cells is mediated by mechanisms involving AMPA receptors, but not by NMDA receptor, during the late phase after reperfusion. YM-90K could provide neuroprotective activity and improve the spatial memory impaired by repeated ischemia. © 2003 Elsevier B.V. All rights reserved.

The spatial memory impairment and expression of apoptotic cells in hippocampal CA1 cells were investigated in rats using single and repeated ischemia models. The neuroprotective and memory-improving effect of YM-90K, an α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, was compared to MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. Twice-repeated ischemia, but not single ischemia, impaired the spatial memory and increased expression of apoptotic cells. YM-90K, given before and 6 h after the second reperfusion, significantly improved the memory and reduced the apoptotic cells 7 days after the second reperfusion in repeated ischemia. MK-801 neither improved the spatial memory nor reduced apoptotic cells. The present study showed that delayed expression of apoptotic cells is mediated by mechanisms involving AMPA receptors, but not by NMDA receptor, during the late phase after reperfusion. YM-90K could provide neuroprotective activity and improve the spatial memory impaired by repeated ischemia. © 2003 Elsevier B.V. All rights reserved.