Treatment potential of LPCN 1144 on liver health and metabolic regulation in a non-genomic, high fat diet induced NASH rabbit model.

PURPOSE: Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. METHODS: Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson's trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. RESULTS: Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p < 0.05) and 1144 + ALPHA (p = 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. CONCLUSIONS: Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.

Testosterone treatment is associated with reduced adipose tissue dysfunction and nonalcoholic fatty liver disease in obese hypogonadal men.

PURPOSE: In both preclinical and clinical settings, testosterone treatment (TTh) of hypogonadism has shown beneficial effects on insulin sensitivity and visceral and liver fat accumulation. This prospective, observational study was aimed at assessing the change in markers of fat and liver functioning in obese men scheduled for bariatric surgery. METHODS: Hypogonadal patients with consistent symptoms (n = 15) undergoing 27.63 ± 3.64 weeks of TTh were compared to untreated eugonadal (n = 17) or asymptomatic hypogonadal (n = 46) men. A cross-sectional analysis among the different groups was also performed, especially for data derived from liver and fat biopsies. Preadipocytes isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglyceride assay and by calculating NAFLD activity score in liver biopsies. RESULTS: In TTh-hypogonadal men, histopathological NAFLD activity and steatosis scores, as well as liver triglyceride content were lower than in untreated-hypogonadal men and comparable to eugonadal ones. TTh was also associated with a favorable hepatic expression of lipid handling-related genes. In visceral adipose tissue and preadipocytes, TTh was associated with an increased expression of lipid catabolism and mitochondrial bio-functionality markers. Preadipocytes from TTh men also exhibited a healthier morpho-functional phenotype of mitochondria and higher insulin-sensitivity compared to untreated-hypogonadal ones. CONCLUSIONS: The present data suggest that TTh in severely obese, hypogonadal individuals induces metabolically healthier preadipocytes, improving insulin sensitivity, mitochondrial functioning and lipid handling. A potentially protective role for testosterone on the progression of NAFLD, improving hepatic steatosis and reducing intrahepatic triglyceride content, was also envisaged. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02248467, September 25th 2014.

Hormonal control and target genes of ftz-f1 expression in the honeybee Apis mellifera: a positive loop linking juvenile hormone, ftz-f1, and vitellogenin.

Ftz-f1 is an orphan member of the nuclear hormone receptor superfamily. A 20-hydroxyecdysone pulse allows ftz-f1 gene expression, which then regulates the activity of downstream genes involved in major developmental progression events. In honeybees, the expression of genes like vitellogenin (vg), prophenoloxidase and juvenile hormone-esterase during late pharate-adult development is known to be hormonally controlled in both queens and workers by increasing juvenile hormone (JH) titres in the presence of declining levels of ecdysteroids. Since Ftz-f1 is known for mediating intracellular JH signalling, we hypothesized that ftz-f1 could mediate JH action during the pharate-adult development of honeybees, thus controlling the expression of these genes. Here, we show that ftz-f1 has caste-specific transcription profiles during this developmental period, with a peak coinciding with the increase in JH titre, and that its expression is upregulated by JH and downregulated by ecdysteroids. RNAi-mediated knock down of ftz-f1 showed that the expression of genes essential for adult development (e.g. vg and cuticular genes) depends on ftz-f1 expression. Finally, a double-repressor hypothesis-inspired vg gene knock-down experiment suggests the existence of a positive molecular loop between JH, ftz-f1 and vg.

Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective molecular mechanisms underlie either short term memory, long term memory, or both. Furthermore, our discovery that administration of rapamycin increased the activation of mTORC2 in microglial cells supports a reappraisal of the beneficial/adverse effects of rapamycin administration.

Increase of neurofilament-H protein in sensory neurons in antiretroviral neuropathy: Evidence for a neuroprotective response mediated by the RNA-binding protein HuD.

Nucleoside reverse transcriptase inhibitors (NRTIs) are key components of HIV/AIDS treatment to reduce viral load. However, antiretroviral toxic neuropathy has become a common peripheral neuropathy among HIV/AIDS patients leading to discontinuation of antiretroviral therapy, for which the underlying pathogenesis is uncertain. This study examines the role of neurofilament (NF) proteins in the spinal dorsal horn, DRG and sciatic nerve after NRTI neurotoxicity in mice treated with zalcitabine (2',3'-dideoxycitidine; ddC). ddC administration up-regulated NF-M and pNF-H proteins with no effect on NF-L. The increase of pNF-H levels was counteracted by the silencing of HuD, an RNA binding protein involved in neuronal development and differentiation. Sciatic nerve sections of ddC exposed mice showed an increased axonal caliber, concomitantly to a pNF-H up-regulation. Both events were prevented by HuD silencing. pNF-H and HuD colocalize in DRG and spinal dorsal horn axons. However, the capability of HuD to bind NF mRNA was not demonstrated, indicating the presence of an indirect mechanism of control of NF expression by HuD. RNA immunoprecipitation experiments showed the capability of HuD to bind the BDNF mRNA and the administration of an anti-BDNF antibody prevented pNF-H increase. These data indicate the presence of a HuD - BDNF - NF-H pathway activated as a regenerative response to the axonal damage induced by ddC treatment to counteract the antiretroviral neurotoxicity. Since analgesics clinically used to treat neuropathic pain are ineffective on antiretroviral neuropathy, a neuroregenerative strategy might represent a new therapeutic opportunity to counteract neurotoxicity and avoid discontinuation or abandon of NRTI therapy.

PARP-1 activation causes neuronal death in the hippocampal CA1 region by increasing the expression of Ca(2+)-permeable AMPA receptors.

An excessive activation of poly(ADP-ribose) polymerases (PARPs) may trigger a form of neuronal death similar to that occurring in neurodegenerative disorders. To investigate this process, we exposed organotypic hippocampal slices to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG, 100µM for 5min), an alkylating agent widely used to activate PARP-1. MNNG induced a pattern of degeneration of the CA1 pyramidal cells morphologically similar to that observed after a brief period of oxygen and glucose deprivation (OGD). MNNG exposure was also associated with a dramatic increase in PARP-activity and a robust decrease in NAD(+) and ATP content. These effects were prevented by PARP-1 but not PARP-2 inhibitors. In our experimental conditions, cell death was not mediated by AIF translocation (parthanatos) or caspase-dependent apoptotic processes. Furthermore, we found that PARP activation was followed by a significant deterioration of neuronal membrane properties. Using electrophysiological recordings we firstly investigated the suggested ability of ADP-ribose to open TRPM2 channels in MNNG-induced cells death, but the results we obtained showed that TRPM2 channels are not involved. We then studied the involvement of glutamate receptor-ion channel complex and we found that NBQX, a selective AMPA receptor antagonist, was able to effectively prevent CA1 neuronal loss while MK801, a NMDA antagonist, was not active. Moreover, we observed that MNNG treatment increased the ratio of GluA1/GluA2 AMPAR subunit expression, which was associated with an inward rectification of the IV relationship of AMPA sEPSCs in the CA1 but not in the CA3 subfield. Accordingly, 1-naphthyl acetyl spermine (NASPM), a selective blocker of Ca(2+)-permeable GluA2-lacking AMPA receptors, reduced MNNG-induced CA1 pyramidal cell death. In conclusion, our results show that activation of the nuclear enzyme PARP-1 may change the expression of membrane proteins and Ca(2+) permeability of AMPA channels, thus affecting the function and survival of CA1 pyramidal cells.

Plant growth regulators and mobilization of reserves in imbibition phases of yellow passion fruit.

The production of seedlings of the passion fruit tree, usually, is sexual, and the seeds are not uniform in the seedling emergence, and soaking treatments of seeds can provide faster and more uniform germination. It was aimed to study the action of plant growth regulators and the mobilization of reserves in the stages of soaking of yellow passion fruit seeds. The seeds were soaked for five hours in solutions containing plant growth regulators, in a completely randomized design, in a factorial 8 x 4, with four replications. The first factor corresponds to eight plant growth regulators: T1 - distilled water (control); T2 - 6-benzylaminepurine ​​500 mg L-1; T3 - 4-(3-indolyl) butyric acid 500 mg L-1; T4 - gibberellic acid 500 mg L-1; T5 - spermine 250 mg L-1; T6 - spermine 750 mg L-1; T7 - spermidine 750 mg L-1; T8 - spermidine 1250 mg L-1; and the second factor, to the four soaking times: zero, four, 72 and 120 hours, corresponding, respectively, to the dry seed, and to phases I, II, and III of the imbibition curve. It was evaluated the biochemical composition of seeds (lipids, soluble sugars and starch). The seeds showed accumulation of lipids in phase III; the content of soluble sugars increased in phase I and decreased in phase II. The starch content increased until the phase II and decreased in phase III. Starch is the main reserve in the seeds and the main source of energy used in phase III; soaking the seeds in polyamines generates an accumulation of lipids in the seeds and soaking in plant growth regulators increases the burning of starch.

Maturation and harvest time of Ateleia glazioveana Baill. seeds.

Ateleia glazioveana Baill. is a pioneer, rustic and can be used for forest recovery. This work aimed to study the process of physiological maturation of this species. The research was carried out in the city of Alegre - ES, the trees were identified in the floral anthesis and accompanied during the filling of the fruits and development of the seeds until the complete maturation. The fruits were harvested at the following stages 7, 14, 21, 28, 35 and 42 days after anthesis, and characterized according to: morphometry, moisture, fresh and dry mass of fruits and seeds, germination, germination speed index, shoot and root length and dry mass of seedlings. The regression equations were adjusted for the main characteristics analyzed as a function of the harvest period. The point of physiological maturity of timbó occurred at 42 days after anthesis.

Care Technologies to Improve Treatment Adherence in Patients Undergoing Organ Transplant: A Scoping Review.

BACKGROUND: The objective of this study was to map care technologies being developed to improve treatment adherence in patients undergoing organ transplant. METHODS: A scoping review was developed according to the Joanna Briggs Institute manual. The research question was developed according to the population, concept, and context strategy. Searches were conducted independently in 6 databases between June and August 2021. The data were evaluated and organized together. The review protocol was published. RESULTS: Fifteen articles were part of the study, mostly published in the United States (33.3%) and in 2016 (33.3%). The main research method identified was clinical studies (80%). Most of the care technologies identified are in relation to medication adherence in the post-transplant setting. Another intervention identified was health education action with the support of mobile apps, electronic monitoring systems, and a card game. CONCLUSIONS: The results present technologies directed at the importance of post-transplant drug adherence; however, it is important to adapt the technologies to the reality experienced by the patient, as well as to train patients so that they can introduce these technologies in their daily lives. Furthermore, it is important that technologies are developed that include other aspects of adherence to post-transplant treatment.

Heavy metals bioconcentration in Crassostrea rhizophorae: A site-to-site transplant experiment at the Potengi estuary, Rio Grande do Norte, Brazil.

In this study, we analyzed the bioconcentration of Cd, Cr, Cu, Pb, Ni, and Zn in the soft tissue of transplanted oysters in two sites in the Potengi estuary for six months. Native oysters collected before and after the transplantation experiment provided the background for statistical analyses. Cd, Cr, and Ni showed a strong inverse correlation with oyster weight in both sites. Transplantation upstream of the estuary presented increasing concentrations of Zn, Cu, and Pb and condition index (CI) and decreasing trends for Cd and Ni, whereas Cr oscillated significantly. In the downstream transplantation, Cu, Pb, and Zn and the CI tended to decrease, whereas for Ni, Cd, and Cr, the concentrations increased. Spatiotemporal principal component analysis correlated these results mainly with proximity to the polluting source, seasonality, and previous exposure to heavy metals. These results helped interpret the responses provided by these biomonitors to environmental changes, whether they are natural or anthropogenic.

Prevalence and severity of dental caries in schoolchildren of Porto, Portugal.

OBJECTIVES: To measure the prevalence and severity of dental caries in adolescents of the city of Porto, Portugal, and to assess socioeconomic and behavioural covariates of dental caries experience. METHODS: A sample of 700 thirteen-year-old schoolchildren was examined. Results from the dental examination were linked to anthropometric information and to data supplied by two structured questionnaires assessing nutritional factors, socio-demographic characteristics and behaviour related to health promotion. Dental caries was measured using the DMFT index, and two dichotomous outcomes, one assessing the prevalence of dental caries (DMFT > 0); the other assessing the prevalence of a high level of dental caries (DMFT > or = 4). RESULTS: Consuming soft drinks derived from cola (irrespective of sugared or diet) two or more times per week, attending a public school, being female and having parents with low educational attainment were identified as risk factors both for having dental caries and for having a high level of dental caries. CONCLUSION: Caries levels were positively associated with frequency of intake of sweetened foods and drinks.

Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies. Neuropathies are associated to aberrant excitability of DRG neurons due to the alteration in the expression or function of a variety of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are overexpressed in inflammatory and neuropathic pain states, and HCN blockers have been shown to reduce neuronal excitability and to ameliorate painful states in animal models. However, HCN channels are critical in cardiac action potential, and HCN blockers used so far in pre-clinical models do not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we show an HCN current gain of function in DRG neurons from oxaliplatin-treated rats. Biochemically, we observed a downregulation of HCN2 expression and an upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion, this study strengthens the evidence for a disease-specific role of HCN1 in CIPN, and proposes HCN1-selective inhibitors as new-generation pain medications with the desired efficacy and safety profile.

Combining in-cell NMR and X-ray fluorescence microscopy to reveal the intracellular maturation states of human superoxide dismutase 1.

An integrated approach which combines in-cell NMR spectroscopy with optical and X-ray fluorescence microscopy was developed to describe the intracellular maturation state of human Cu,Zn-SOD1. Microscopy data show a correlation between the intracellular levels of SOD1 and the content of zinc, corresponding to zinc binding to SOD1 observed by in-cell NMR.

Transferencia de atención prehospitalaria entre equipos de salud: revisión integradora / Pre-hospital healthcare attention transference among health teams: an integrative review / Transferência de atenção pré-hospitalar entre equipes de saúde: revisão integrativa

Resumen Introducción: Las transferencias de atención efectivas permiten satisfacer las necesidades de continuidad de la atención; sin embargo, pocos estudios se centran en comunicar información al respecto. Objetivo: Analizar la evidencia disponible en la literatura sobre la transferencia de atención prehospitalaria entre los equipos de salud. Metodología: Revisión integradora. La búsqueda de estudios primarios se realizó en cuatro bases de datos (PubMed, CINAHL, LILACS, Scopus). La muestra consistió en 20 investigaciones, que se agruparon en dos categorías. Resultados: La síntesis de la evidencia indicó las estrategias empleadas por los equipos de salud para estandarizar la comunicación de información durante la transferencia de la atención prehospitalaria y las circunstancias que intervienen en este momento. Entre las estrategias destacamos el uso de un formulario de ambulancia para utilizar en los servicios que continuarán la atención. Las circunstancias intermedias incluyen demoras en la transferencia y fallas en la información/comunicación. Discusión: El uso de mnemónicos y protocolos para una mejor transferencia no es generalizado, pero existe consenso que la falta de procesos de comunicación integrados contribuyen a las fallas en la atención. Conclusión: Las transferencias efectivas de atención son complejas ya que hay varios factores que intervienen en su proceso, los cuales dependen de negociaciones y acuerdos entre los equipos de salud y los gerentes.

Abstract Introduction: An effective attention transference allows the continuity of healthcare; however, not many studies in the literature are focused on this important process. Objective: To analyze the available evidence regarding the transference of healthcare attention among healthcare teams at the prehospital stage. Methodology: This is an integrative review. The primary search was conducted on the PubMed, CINAHL, LILACS, and Scopus databases. The sample was constituted by 20 research studies which were further grouped into two categories. Results: The synthesis showed some of the strategies which are used by health teams to standardize the information transmission during the transference of healthcare attention at the prehospital stage. One of these strategies is, while still in the ambulance, the use of checklists to be further be used by the health teams continuing the attention at the hospital. Some related issues included delays in the transference and errors in the communications. Discussion: The use of mnemonics and protocols to improve the transference process is not generalized, and there is consensus that the lack of integration in the communications is a major cause of errors during the attention transference. Conclusion: Achieving an effective healthcare attention transference can be complex due to the several factors. One of these key factors was found to be related to the agreements among healthcare teams and managers.

Resumo Introdução: As transferências de atenção efetivas permitem satisfazer as necessidades de continuidade do atendimento; porém, poucos estudos se centram em comunicar informação a esse respeito. Objetivo: Analisar a evidência disponível na literatura sobre a transferência do atendimento pré-hospitalar entre equipes de saúde. Metodologia: Revisão integrativa. A busca de estudos primários realizou-se em quatro bases de dados (PubMed, CINAHL, LILACS, Scopus). A amostra consistiu em 20 pesquisas, que se agruparam em duas categorias. Resultados: A síntese da evidência apontou as estratégias empregadas pelas equipes de saúde para estandardizar a comunicação de informação durante a transferên-cia da atenção pré-hospitalar e as circunstâncias que intervém neste momento. Dentre as estratégias salientamos o uso de um formulário de ambulância para utilizar nos serviços que continuarão o atendimento. Circunstâncias intermediárias incluem demoras na transferência e falhas na informação/comunicação. Discussão: O uso de mnemônicos e protocolos para uma melhor transferência não é generalizado, mas existe consenso que a falta de processos de comunicação integrados contribui às falhas no atendimento. Conclusão: As transferências efetivas de atendimento são complexas já que há vários fatores que interferem em seu processo, os quais dependem de negociações e acordos entre as equipes de saúde e os gestores.

The RNA-binding protein HuD promotes spinal GAP43 overexpression in antiretroviral-induced neuropathy.

Nucleoside reverse transcriptase inhibitors (NRTIs) are known to produce painful neuropathies and to enhance states of pain hypersensitivity produced by HIV-1 infection in patients with AIDS leading to discontinuation of antiretroviral therapy, thus limiting viral suppression strategies. The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. In the current study, we tested the hypothesis that HuD, an RNA binding protein known to be an essential promoter of neuronal differentiation and survival, might be involved in the response to NRTI-induced neuropathy. Antiretroviral neuropathy was induced by a single intraperitoneal administration of 2',3'-dideoxycytidine (ddC) in mice. HuD was physiologically expressed in the cytoplasm of the soma and in axons of neurons within DRG and spinal cord and was considerably overexpressed following ddC treatment. ddC up-regulated spinal GAP43 protein, a marker of neuroregeneration, and this increase was counteracted by HuD silencing. GAP43 and HuD colocalize in DRG and spinal dorsal horn (SDH) axons and administration of an anti-GAP43 antibody aggravated the ddC-induced axonal damage. The administration of a protein kinase C (PKC) inhibitor or the PKCγ silencing prevented both HuD and GAP43 increased expression. Conversely, treatment with the PKC activator PDBu potentiated HuD and GAP43 overexpression, demonstrating the presence of a spinal PKC-dependent HuD-GAP43 pathway activated by ddC. These results indicated that HuD recruitment and GAP43 protein increase are mechanistically linked events involved in the response to antiretroviral-induced neurodegenerative processes.

Cell fusion promotes chemoresistance in metastatic colon carcinoma.

Chemoresistance is an important concern in the treatment of metastatic colon cancer. It may emerge through selection of clones that are inherently resistant from the outset or through mechanisms acquired during treatment. Cell fusion represents an efficient means of rapid phenotypic evolution that make cells with new properties at a rate exceeding that achievable by random mutagenesis. Here, we first identified a number of proteins involved in cell fusion using a shotgun proteomics approach, then we investigated the role of these proteins namely tetraspanin CD81/CD9, ADAM10, GTP-binding protein α13, radixin, myosin regulatory light chain and RhoA in the regulation of colon cancer cell fusion. We also found a previously unrecognized role of ADAM10, Gα13 and RhoA in promoting cell fusion. Finally, we show that the occurrence of cell fusion in a metastatic model of colon carcinoma causes the appearance of cells resistant to both 5-fluorouracil and oxaliplatin. These findings highlight the importance of cell fusion in cancer progression and raise significant implications for overcoming chemoresistance in metastatic colon cancer.

Habilidades sociais e vivência acadêmica de estudantes universitários / Social skills and academic integration of college students

O estudo objetivou caracterizar os universitários quanto ao repertório de habilidades sociais e àvivência acadêmica, examinando a correlação entre tais variáveis e comparando as diferenças porgênero e curso. Participaram 202 alunos de Informática e Psicologia, com idades entre 16 e 49 anos(M = 22,84; DP = 5,92), sendo 75,6% (n = 146) homens, que responderam ao Questionário deVivência Acadêmica – reduzido, Escala de Avaliação da Vida Acadêmica e Inventário de HabilidadesSociais. Os resultados indicaram percepção moderada da vivência acadêmica e do repertório dehabilidades sociais e correlações de baixa magnitude entre essas variáveis. Diferenças entre os cursose entre os sexos foram identificadas. Os achados são discutidos com base na literatura e novaspesquisas são sugeridas(AU)

The adenosine A2A receptor antagonist ZM241385 enhances neuronal survival after oxygen-glucose deprivation in rat CA1 hippocampal slices.

BACKGROUND AND PURPOSE: Activation of adenosine A(2A) receptors in the CA1 region of rat hippocampal slices during oxygen-glucose deprivation (OGD), a model of cerebral ischaemia, was investigated. EXPERIMENTAL APPROACH: We made extracellular recordings of CA1 field excitatory postsynaptic potentials (fepsps) followed by histochemical and immunohistochemical techniques coupled to Western blots. KEY RESULTS: OGD (7 or 30 min duration) elicited an irreversible loss of fepsps invariably followed by the appearance of anoxic depolarization (AD), an unambiguous sign of neuronal damage. The application of the selective adenosine A(2A) receptor antagonist, ZM241385 (4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo{2,3-a}{1,3,5}triazin-5-ylamino]ethyl)phenol; 100-500 nmolxL(-1)) prevented or delayed AD appearance induced by 7 or 30 min OGD and protected from the irreversible fepsp depression elicited by 7 min OGD. Two different selective adenosine A(2A) receptor antagonists, SCH58261 and SCH442416, were less effective than ZM241385 during 7 min OGD. The extent of CA1 cell injury was assessed 3 h after the end of 7 min OGD by propidium iodide. Substantial CA1 pyramidal neuronal damage occurred in untreated slices, exposed to OGD, whereas injury was significantly prevented by 100 nmolxL(-1) ZM241385. Glial fibrillary acid protein (GFAP) immunostaining showed that 3 h after 7 min OGD, astrogliosis was appreciable. Western blot analysis indicated an increase in GFAP 30 kDa fragment which was significantly reduced by treatment with 100 nmolxL(-1) ZM241385. CONCLUSIONS AND IMPLICATIONS: In the CA1 hippocampus, antagonism of A(2A) adenosine receptors by ZM241385 was protective during OGD (a model of cerebral ischaemia) by delaying AD appearance, decreasing astrocyte activation and improving neuronal survival.

Culture conditions affect proliferative responsiveness of olfactory ensheathing glia to neuregulins.

Olfactory ensheathing glia (OEG) have been used to improve outcome after experimental spinal cord injury and are being trialed clinically. Their rapid proliferation in vitro is essential to optimize clinical application, with neuregulins (NRG) being potential mitogens. We examined the effects of NRG-1beta, NRG-2alpha, and NRG3 on proliferation of p75-immunopurified adult OEG. OEG were grown in serum-containing medium with added bovine pituitary extract and forskolin (added mitogens) or in serum-containing medium (no added mitogens). Cultures were switched to chemically defined medium (no added mitogens or serum), NRG added and OEG proliferation assayed using BrdU. OEG grown initially with added mitogens were not responsive to added NRGs and pre-exposure to forskolin and pituitary extract increased basal proliferation rates so that OEG no longer responded to added NRG. However, NRG promoted proliferation but only if cells were initially grown in mitogen-free medium. Primary OEG express ErbB2, ErbB3, and small levels of ErbB4 receptors; functional blocking indicates that ErbB2 and ErbB3 are the main NRG receptors utilized in the presence of NRG-1beta. The long-term stimulation of OEG proliferation by initial culture conditions raises the possibility of manipulating OEG before therapeutic transplantation.