A single dose of S‐ketamine induces long‐term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation

Ketamine, an antagonist of N‐methyl‐d ‐aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived + saline; nondeprived + S‐ketamine (15 mg/kg); deprived + saline; deprived + S‐ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive‐like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive‐like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long‐term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long‐term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1268–1281, 2015     

An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune etiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applied for dengue fever.     

Indole-2-carboxamidines as novel NR2B selective NMDA receptor antagonists

A novel series of indole-2-carboxamidine derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the substituents on the indole skeleton as well as the substitution of the benzyl moiety on the biological activity of the compounds was studied. Compound 5a was po active in the formalin test in mouse.     

Enhanced NTPDase and 5′-nucleotidase activities in diabetes mellitus and iron-overload model

The activity of the enzymes NTPDase and 5′-nucleotidase was studied in both diabetes mellitus and an associated model of iron-overload. Rats were divided in five groups: citrate (CC), saline (S), diabetic (D), iron-overload (IO), and diabetic iron-overload (DIO). Diabetes was induced with alloxan (150 mg/kg), and iron-overload was induced with iron-dextran (10 intramuscular applications of ±80 mg/kg). The enzymatic activities were evaluated in the platelets. The results demonstrated an increase in the activity of NTPDase with substrates ATP and ADP (60% and 120%, respectively; P < 0.001), and 5′-nucleotidase (60%, P < 0.001). This increase was more intense in the IO and DIO groups. The results obtained in vitro showed an activation in ATP, ADP, and AMP hydrolysis between 1 μM and 1,000 μM ferric nitrate concentrations, being more pronounced at 100 μM and decreasing at 1,000 μM. We concluded that diabetes mellitus in association with iron-overload increased the hydrolysis of adenine nucleotides in platelets, contributing to the abnormalities found in these pathological conditions.     

Biogas digester for palm oil mill wastes and 1.8 Mw generating system in Gunung Meliau,with linkage to Pontianak system

Summary In a common palm-oil industry 400 tons of fresh fruit bunches are processed each day. The wastes resulting from this processing (64% in weight of the fresh fruit) are burned to produce the steam needed in the processing while the sludge waters are discharged in rivers. A biogas plant of 4×4000 m³ would produce 24 000 m³ biogas per day. If the production, of fertilizer (40 tons/day) is included in the rentability study, the pay-back time is 9 years and the unit cost $US 0.06 per kWh.

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Resumen En una industria tipo de obtención de aceite de palma se processan más de 400 toneladas diarias de frutos frescos. Los residuos de este proceso (64% del peso fresco de los frutos) se queman para producir el vapor que se necesita en el proceso mientras las aguas residuales se vierten en ríos. Una planta de biogas de 4×4000 m³ produciría 24000 m³ de biogas diarios. Si la producción de fertilizante se incluye en el estudio de rentabilidad, el tiempo de amortización es de 9 años y el coste de la unidad de 0.06 $USA por Kwh.

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Résumé Dans une industrie de production d'huile de palme, 400 tonnes de noix de palme sont transformées chaque jour. Les déchets résultant de cette transformation (64% en poids du fruit frais) sont brûlés pour produire de la vapeur nécessaire au cours du processus, tandis que les boues résiduaires sont déchargées dans les cours d'eau. Une installation de biométhanisation de 4×4000 m³ traitant l'ensemble de ces déchets pourrait produire 24 000 m³ de biogaz par jour. Si on prend en compte dans l'étude de rentabilité la production d'un effluent à valeur fertilisante à raison de 40 tonnes par jour, le temps de, recouvrement de l'investissement serait de 9 ans et le prix unitaire du kWh de 0.06 dollars US.

     

The importance of considering both taxonomic and habitat guild approaches in small mammal research

Studies on the effects of habitat fragmentation on small mammals often lead to confounding results as they only consider taxonomic groups in their analysis and neglect functional diversity of the communities. Here we describe the structure and composition of small mammal communities at 22 sites, ranging from 41 to 7035 ha, in a hyper‐fragmented landscape of an Amazonia‐Cerrado ecotone. Also, in considering a taxonomic and habitat guild approach, we report the effects of habitat structures and patch spatial attributes on richness, abundance and species composition. Small mammal richness reported in southern Amazonia (N = 23 species) is greater than most previous studies in the tropics. All rare small mammals captured in this study were forest interior species. Richness of forest interior species was positively related to larger patches, as shown by the species–area relationship. However, 52% of the small mammal species were in forest fragments smaller than 50 ha, highlighting the importance of preserving both large and small forest fragments in a landscape with accelerated habitat reduction. Richness of edge‐tolerant species was not associated with the tested variables, yet edge‐tolerant species were more abundant in degraded environments. Marsupials were positively associated with vertical habitat structures, while rodents were more strongly related to a ground‐level habitat structure. The landscape studied is extremely variable and has contributed to the difficulty in detecting clear patterns, particularly when considering only one approach. Because of the complementary outputs when analysing either taxonomic groups or habitat guilds, we recommend the use of multi‐taxa studies of different guilds to assist decision makers in designing conservation strategies and appropriate management of small mammal populations.     

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A low-protein diet during pregnancy alters glucose metabolism and insulin secretion

In pancreatic islets, glucose metabolism is a key process for insulin secretion, and pregnancy requires an increase in insulin secretion to compensate for the typical insulin resistance at the end of this period. Because a low-protein diet decreases insulin secretion, this type of diet could impair glucose homeostasis, leading to gestational diabetes. In pancreatic islets, we investigated GLUT2, glucokinase and hexokinase expression patterns as well as glucose uptake, utilization and oxidation rates. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. The insulin secretion in 2.8 mmol l(-1) of glucose was higher in islets from LPP rats than that in islets from CP, CNP and LPNP rats. Maximal insulin release was obtained at 8.3 and 16.7 mmol l(-1) of glucose in LPP and CP groups, respectively. The glucose dose-response curve from LPNP group was shifted to the right in relation to the CNP group. In the CP group, the concentration-response curve to glucose was shifted to the left compared with the CNP group. The LPP groups exhibited an "inverted U-shape" dose-response curve. The alterations in the GLUT2, glucokinase and hexokinase expression patterns neither impaired glucose metabolism nor correlated with glucose islet sensitivity, suggesting that β-cell sensitivity to glucose requires secondary events other than the observed metabolic/molecular events.     

CFTR gene transfer to human cystic fibrosis pancreatic duct cells using a Sendai virus vector

Cystic fibrosis (CF) is a fatal inherited disease caused by the absence or dysfunction of the CF transmembrane conductance regulator (CFTR) Cl- channel. About 70% of CF patients are exocrine pancreatic insufficient due to failure of the pancreatic ducts to secrete a HCO3- -rich fluid. Our aim in this study was to investigate the potential of a recombinant Sendai virus (SeV) vector to introduce normal CFTR into human CF pancreatic duct (CFPAC-1) cells, and to assess the effect of CFTR gene transfer on the key transporters involved in HCO3- transport. Using polarized cultures of homozygous F508del CFPAC-1 cells as a model for the human CF pancreatic ductal epithelium we showed that SeV was an efficient gene transfer agent when applied to the apical membrane. The presence of functional CFTR was confirmed using iodide efflux assay. CFTR expression had no effect on cell growth, monolayer integrity, and mRNA levels for key transporters in the duct cell (pNBC, AE2, NHE2, NHE3, DRA, and PAT-1), but did upregulate the activity of apical Cl-/HCO3- and Na+/H+ exchangers (NHEs). In CFTR-corrected cells, apical Cl-/HCO3- exchange activity was further enhanced by cAMP, a key feature exhibited by normal pancreatic duct cells. The cAMP stimulated Cl-/HCO3- exchange was inhibited by dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2-DIDS), but not by a specific CFTR inhibitor, CFTR(inh)-172. Our data show that SeV vector is a potential CFTR gene transfer agent for human pancreatic duct cells and that expression of CFTR in CF cells is associated with a restoration of Cl- and HCO3- transport at the apical membrane.