Socioeconomic factors and the probability of death by Covid-19 in Brazil.

BACKGROUND: To design better measures to contain the Covid-19 epidemics, it is relevant to know whether socioeconomic factors are associated with a higher risk of death by Covid-19. This work estimates the effects of individual socioeconomic characteristics on the risk of death by Covid-19. METHODS: Logistic models were estimated to assess the effect of socioeconomic characteristics (income, race/ethnicity, schooling, occupation and economic activity) on the risk of death from Covid-19. For this purpose, Covid-19 individual death records in Rio de Janeiro state, Brazil were combined with the Annual Register of Social Information, which contains socioeconomic information about formal workers. FINDINGS: Workers employed in establishments in the health and public safety sectors present a risk of dying 2.46 and 2.25 times higher than those employed in other activities. Non-white people, men, and those who work in the Metropolitan Region are also more likely to die from Covid-19. People with higher education are 44% less likely to die from the disease. CONCLUSIONS: Some population groups are more vulnerable to the Covid-19 pandemic and individual socioeconomic conditions play a relevant role in the probability of death by the disease. That should be considered in the design of prevention policies to be adopted.

Facilitation of fear extinction by novelty is modulated by ß-adrenergic and 5-HT1A serotoninergic receptors in hippocampus.

Extinction is the learned inhibition of retrieval of a previously acquired memory and is a major component of exposure therapy, which has attracted much attention because of the use in the treatment of drug addiction, phobias and particularly fear disorders such as post-traumatic stress disorder (PTSD). Exposure to a novel environment before or after extinction training can enhance the extinction of contextual fear conditioning, however the cellular and molecular substrates are still unclear. Here, we investigated the participation of H2-histaminergic, ß-adrenergic and 5-HT1A-serotonergic receptors of the hippocampus on the enhancement of extinction memory caused by novelty. The infusion into the CA1 region of the serotonin 5-HT1A-receptor agonist, 8-OH-DPAT and the ß-adrenergic blocker, Timolol, after the exposure to the novelty hindered the enhancement of extinction by novelty, while Timolol also hindered the extinction consolidation when infused post-extinction. These impairments were abolished by the coinfusion of 8-OH-DPAT plus the 5-HT1A receptor antagonist, NAN-190 and Timolol plus ß-adrenergic agonist, Isoproterenol. However, Dimaprit and Ranitidine blocked the retrieval of CFC, but did not prevented the extinction learning. Here we elucidated some of the molecular mechanisms that are involved on the enhancement of extinction by novelty, demonstrating that the ß-adrenoreceptors and 5-HT1A serotonergic receptors participate on this process alongside with dopaminergic D1 receptors previously described, while histamine H2 receptors, so ubiquitous in learning-related functions in hippocampus are not involved.

P2X7 receptor and klotho expressions in diabetic nephropathy progression.

Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X7), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X7 and klotho in several stages of diabetes in rats. Diabetes was induced in Wistar rats by streptozotocin, while the control group rats received the drug vehicle. From the 1st to 8th weeks after the diabetes induction, the animals were placed in metabolic cages on the 1st day of each week for 24 h to analyze metabolic parameters and for the urine collection. Then, blood samples and the kidneys were collected for biochemical analysis, including Western blotting and qPCR for P2X7 and klotho. Diabetic rats presented a progressive loss of renal function, with reduced nitric oxide and increased lipid peroxidation. The P2X7 and klotho expressions were similar up to the 4th week; then, P2X7 expression increased in diabetes mellitus (DM), but klotho expression presented an opposite behavior, until the 8th week. Our data show an inverse correlation between P2X7 and klotho expressions through the development of DM, which suggests that the management of these molecules could be useful for controlling the progression of this disease and diabetic nephropathy.

Pharmaco-parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle.

The goals of the current study were to evaluate the potential pharmacokinetic (PK) interactions and the clinical efficacy occurring after the subcutaneous (s.c.) administration of ricobendazole (RBZ) and levamisole (LEV) given both separately and co-administered to calves naturally infected with susceptible gastrointestinal nematodes. The clinical efficacy was shown in two seasons, winter and spring, with predominance of different nematode populations. Groups of 15 calves were treated with RBZ alone, LEV alone and RBZ + LEV combination, and an untreated group was kept as a Control. RBZ and LEV plasma concentrations were quantified by HPLC. The clinical efficacy was determined by the faecal egg count reduction test. RBZ and LEV have similar plasma persistence, being detected in plasma over 24 hr post-treatment. No PK interactions were observed after the combined treatment, with similar PK parameters (p > .05) obtained for the single-drug and the combination-based strategy. In winter, the observed clinical efficacies were 96%, 99% and 100% for groups treated with RBZ, LEV and RBZ + LEV, respectively; however, in spring, the efficacies were 95%, 93% and 96% for the same groups. Remarkably, the combination was the only treatment that achieved 100% clinical efficacy against both Haemonchus spp and Ostertagia spp in winter; but the increased presence of Ostertagia spp. in spring (28% in untreated group) determined a tendency to reduced efficacies compared to winter time (only 10% of Ostertagia spp. in untreated group), even for the combined treatment. Overall, in a scenario where the nematode population is susceptible, the RBZ + LEV treatment may be a valid combination in cattle to delay the development of resistance, especially in winter when this combination achieved 100% of efficacy. Thus, selection of anthelmintic resistance will never occur. In fact, this is one of the greatest challenges for the whole cattle production system: to be one step ahead of anthelmintic resistance.

Benzofuroxan derivatives N-Br and N-I induce intrinsic apoptosis in melanoma cells by regulating AKT/BIM signaling and display anti metastatic activity in vivo.

BACKGROUND: Malignant melanoma is an aggressive type of skin cancer, and despite recent advances in treatment, the survival rate of the metastatic form remains low. Nifuroxazide analogues are drugs based on the substitution of the nitrofuran group by benzofuroxan, in view of the pharmacophore similarity of the nitro group, improving bioavailability, with higher intrinsic activity and less toxicity. Benzofuroxan activity involves the intracellular production of free-radical species. In the present work, we evaluated the antitumor effects of different benzofuroxan derivatives in a murine melanoma model. METHODS: B16F10-Nex2 melanoma cells were used to investigate the antitumor effects of Benzofuroxan derivatives in vitro and in a syngeneic melanoma model in C57Bl/6 mice. Cytotoxicity, morphological changes and reactive oxygen species (ROS) were assessed by a diphenyltetrasolium reagent, optical and fluorescence microscopy, respectively. Annexin-V binding and mitochondrial integrity were analyzed by flow cytometry. Western blotting and colorimetry identified cell signaling proteins. RESULTS: Benzofuroxan N-Br and N-I derivatives were active against murine and human tumor cell lines, exerting significant protection against metastatic melanoma in a syngeneic model. N-Br and N-I induce apoptosis in melanoma cells, evidenced by specific morphological changes, DNA condensation and degradation, and phosphatidylserine translocation in the plasma membrane. The intrinsic mitochondrial pathway in B16F10-Nex2 cells is suggested owing to reduced outer membrane potential in mitochondria, followed by caspase -9, -3 activation and cleavage of PARP. The cytotoxicity of N-Br and N-I in B16F10-Nex2 cells is mediated by the generation of ROS, inhibited by pre-incubation of the cells with N-acetylcysteine (NAC). The induction of ROS by N-Br and N-I resulted in the inhibition of AKT activation, an important molecule related to tumor cell survival, followed by upregulation of BIM. CONCLUSION: We conclude that N-Br and N-I are promising agents aiming at cancer treatment. They may be useful in melanoma therapy as inducers of intrinsic apoptosis and by exerting significant antitumor activity against metastatic melanoma, as presently shown in syngeneic mice.

A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes.

PURPOSE: To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT, evaluating the response in subgroups with different GPx1 genotypes. METHODS: CAT patients (n = 55) with positive antiTPO were randomized to selenomethionine (SeMet) 200 µg daily (n = 28) or placebo (n = 27) for 3 months. Assessments included GPx1 genotyping at baseline and serum levels of plasma selenium, erythrocyte GPx1 activity, antiTPO and thyroid echogenicity at baseline, and 3 and 6 months. RESULTS: In the SeMet group, the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes. In the overall cohort, patients randomized to SeMet showed a 5 % decrease in antiTPO levels at 3 months (p = non-significant) and 20 % at 6 months (p < 0.001 versus 3 months). In contrast, patients in the placebo group did not show significant changes in antiTPO levels at any time point. Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet. CONCLUSIONS: Selenium supplementation decreased serum antiTPO levels in CAT patients, with similar response among patients with different GPx1 genotypes.

[Evolution of functional capacity of older people during hospital stay]. / Evolución de la capacidad funcional en adultos mayores hospitalizados en la unidad geriátrica de agudos del Hospital Clínico de la Universidad de Chile.

BACKGROUND: Up to 70% of hospitalized older people experience a deterioration of their functional capacity during the course of hospital stay. This change has a dismal effect of quality of life and prognosis. AIM: To assess the change in functional status of older people during the course of hospitalization in a geriatric unit. MATERIAL AND METHODS: Review of medical records of 83 patients with a mean age of 79 years (70% women), hospitalized in an acute geriatric unit of a clinical hospital, between 2007 and 2009. Functional capacity was assessed using Barthel and Lawthon scales in a basal period, on admission and on discharge. RESULTS: Mean hospital stay was nine days. Median scores of Barthel scale on the basal period, on admission and on discharge were 90, 50 and 80, respectively. The figures for Lawthon scale were 4,2 and 3 respectively. Seventy eight percent of patients lost functional capacity during hospital stay and 72% recovered their functional status on discharge. CONCLUSIONS: A great proportion of older people experience a loss of functional capacity during hospitalization. This deterioration can be reverted with an adequate geriatric management.

Acute toxicity of essential oils of Aloysia triphylla (L'Hér.) Britton, Lippia gracilis Schauer, and Piper aduncum L. in Colossoma macropomum (Cuvier, 1818).

The aim of this study was to determine the acute toxicity of the essential oils (EOs) of Aloysia triphylla, Lippia gracilis and Piper aduncum in juvenile tambaqui (Colossoma macropomum), and evaluate the possible histopathological alterations in their gills. For the acute toxicity tests, juvenile tambaqui (n=24/treatment) were distributed in six treatments with three replicates, which comprised the control and five EO concentrations of A. triphylla (60, 80, 100, 120 and 140 mg L-1), L. gracilis (35, 40, 45, 50 and 55 mg L-1) and P. aduncum (42.5, 45, 47.5, 50 and 52.5 mg L-1), with an exposure period of 4 h. The mortality rate and severity of damage to the tambaqui gills were proportional to the increase in the concentration of the EO, with LC50-4 h values estimated at 109.57 mg L -1 for A. triphylla, 41.63 mg L -1 for L. gracilis and 48.17 mg L -1 for P. aduncum. The main morphological damages observed in the gills of the tambaqui exposed to the three EOs, were Grade I: hypertrophy and hyperplasia of lamellar epithelial cells, lamellar fusion, epithelial detachment, capillary dilation and constriction, proliferation of chloride cells and mucosal cells and edema; in low frequency Grade II damage as epithelial rupture and lamellar aneurysm. Necrosis (Grade III damage) was observed only in gill lamellae exposed to P. aduncum EO (47.5, 50.0 and 52.5 mg L-1). Concentrations of EOs below LC50-4 h can be used sparingly, for short periods of exposure for the treatment of diseases in tambaqui breeding.

Calcium pyruvate in the attenuation of the water deficit on the agro-industrial quality of ratoon sugarcane.

Sugarcane is one of the largest agricultural commodities when considering the export volume and the number of jobs generated. Sugarcane production in the Brazilian Northeast region is generally low due to several factors, including the irregular rainfall distribution, which highlights the importance of studies aimed at mitigating the deleterious effects of water stress. In this scenario, this study aimed to evaluate calcium pyruvate as a water deficit attenuator on the agro-industrial quality of sugarcane in the second cycle of cultivation. The experiment was conducted out under greenhouse conditions of the Federal University of Campina Grande, where five sugarcane commercial genotypes tested (G1- RB863129, G2- RB92579, G3- RB962962, G4- RB021754, and G5- RB041443) and three irrigation management strategies (E1- full irrigation, E2- water deficit with application of 30 mM of calcium pyruvate, and E3- water deficit without calcium pyruvate application), distributed in randomized blocks in 5 × 3 factorial arrangement with three replications. The RB021754 genotype under water deficit and without foliar application of calcium pyruvate increased the fiber content (13.2%) and the sugarcane moist cake weight (143.5 g). The effects of water deficit in sugarcane genotypes are attenuated by the exogenous application of 30 mM of calcium pyruvate, with benefits on the polarized sucrose content, apparent sucrose content of the juice, soluble solids content, purity, corrected cane POL, total recoverable sugars, and stem mass in relation to plants under water deficit without calcium pyruvate application.

Albendazole sulphoxide kinetic disposition after treatment with different formulations in dogs.

New therapeutic strategies based on the search of alternative formulations of albendazole (ABZ) and albendazole sulphoxide (ABZSO) are under current development to optimize posology and antiparasite efficacy in dogs. In an incomplete block design, nine dogs were randomly divided into three groups (n = 6). Treatments were carried out in two phases as follows. Phase I: Group I (treatment A), animals received ABZ at 25 mg/kg of conventional formulation. Group II (treatment B), dogs received 25 mg/kg of a modified poloxamer-ABZ formulation. Group III (treatment C), animals were treated with ABZSO in equimolar amount to ABZ doses. After 21 days of wash-out period the experiment was repeated (Phase II). Blood samples were collected over 24 h and subsequently analysed by high performance liquid chromatography. ABZSO and ABZSO(2) were the analytes recovered in plasma. Significant higher (P < 0.001) ABZSO area under the concentration-time curve (+500%) and C(max) (+487%) values were obtained for the treatment C in comparison with treatments A and B. However, no statistical differences on pharmacokinetic parameters were found between formulations A and B. In conclusion, the enhanced plasma concentration profile obtained for the ABZSO formulation used in treatment C may contribute to optimize the anthelmintic control in dogs.

[Cost analysis of early diagnosis of hydatidosis in children of 5 and 12 years old in the province of Ñuble, Bío-Bío Region, Chile]. / Estimación del costo para el diagnóstico precoz de la hidatidosis en niños de 5 y 12 años en la provincia de Ñuble, Región del Bío-Bío, Chile.

This study conducted a cost analysis of different interventions in the early diagnosis of hydatidosis between the years 2006 -2007 in the Province of Nuble, Bio-Bio Region of Chile. The aim was to estimate the costs of early diagnosis of this condition. We included all children of 5 and 12 years old in rural areas of the province. Data collection activities were identified which included specific antibody measurements (indirect ELISA) and an abdominal ultrasound. For the determination of costs, direct and indirect costs were identified using the methodology of activity-based costs. The results demonstrate that the preventive diagnosis costs S17.183 Chilean pesos per child (S35 US dollars), thus making this intervention of lower cost than waiting until the person becomes ill with this disease.

Combined moxidectin-levamisole treatment against multidrug-resistant gastrointestinal nematodes: A four-year efficacy monitoring in lambs.

Nematicide combinations may be a valid strategy to achieve effective nematode control in the presence of drug resistance. The goal of the current trial was to evaluate the pharmaco-parasitological performance of the moxidectin (MOX) and levamisole (LEV) combination after four years of continuous use in lambs naturally parasitized with multi-resistant gastrointestinal nematodes. At the beginning of the trial, 40 lambs were divided into four groups (n = 10), which were untreated (control) or subcutaneously treated with MOX (0.2 mg/kg), LEV (8 mg/kg) or with the combination MOX + LEV (administered separately at 0.2 and 8 mg/kg, respectively). Blood samples were collected at different times post-treatment and LEV and MOX plasma concentrations were measured by HPLC. The clinical efficacy of the continuous use of MOX + LEV combination was assessed with the controlled efficacy test (CET), performed at the beginning and end of the study, and with the faecal egg count reduction (FECR) test, performed over the four-year study period. No significant adverse pharmacokinetic changes were observed either for MOX or LEV after their co-administration to infected lambs. The CET (first year) showed efficacies of 84.3 % (Haemonchus contortus), 100 % (Teladorsagia circumcincta and Trichostrongylus axei), and 97.4 % (T. colubriformis). After the repetitive use of the combined treatment for four years, those efficacies remained high (100 %) and only decreased to 58 % against T. colubriformis. The evaluation of the FECR over the study period showed fluctuations in the performance of the combined administration. The initial FECR (2014) was 99 % (MOX), 85 % (LEV) and 100 % (MOX + LEV). The co-administration of MOX + LEV during the four-year experimental period resulted in a significantly higher anthelmintic effect (87 %) than that of MOX (42 %) or LEV (69 %) given alone. The combined use of MOX + LEV to control resistant gastrointestinal nematodes appears to be a valid strategy under specific management conditions. A high initial therapeutic response to the combination would be a relevant feature for the success of this tool.

Licking induced changes to the pattern of moxidectin milk elimination after topical treatment in dairy cows.

Pour-on administration of the macrocyclic lactones anti-parasitic compounds in beef and dairy cattle is now worldwide accepted. However, the information available on their milk excretion pattern, after topical administration is rather limited. Additionally, the cattle licking behaviour has been proven to affect the kinetics of these anti-parasitic compounds. The purpose of this study was to investigate the influence of the natural licking behaviour on the plasma and milk disposition of moxidectin (MXD), topically administered (500 microg/kg) in lactating dairy cows. Ten lactating Holstein dairy cows (705 kg body weight) were allocated into two experimental groups (n = 5). The licking was prevented during 5 days postadministration in animals in group I, and the remaining cows (group II) were allowed to lick freely. MXD concentrations profiles were measured in plasma and milk over 15 days posttreatment. The licking restriction period caused marked changes in MXD disposition kinetics both in plasma and milk. Both plasma and milk MXD concentrations (partial AUC 0-5 days) were significantly lower (P < 0.05) in licking-restricted cows. After the 5-day of restriction period, the animals were allowed to lick freely, which permitted the oral ingestion of MXD, situation clearly reflected both in plasma profile and milk excretion pattern. Despite the enhanced MXD milk concentrations measured in free-licking cows, drug concentrations did not reach the maximum MXD residues limit.

Failure of ivermectin and eprinomectin to control Amblyomma parvum in goats: characterization of acaricidal activity and drug pharmacokinetic disposition.

The therapeutic efficacies of ivermectin (subcutaneous injection) and eprinomectin (topical treatment) given at two different dosage levels to goats naturally infested with Amblyomma parvum were assessed. Treatments included subcutaneous injection of ivermectin at 0.2 and 0.4mg/kg and extra-label pour-on administration of eprinomectin at 0.5 and 1mg/kgb.w. Ivermectin and eprinomectin failed to control Amblyomma parvum on goats. Treatment with ivermectin resulted in a low number of engorged female ticks in relation to untreated control goats and, at the highest dose rate (0.4mg/kg), the female engorgement weights were significantly lower and the pre-oviposition period significantly longer than those observed in ticks recovered from untreated control goats. The tick efficacy assessment was complemented in a separate group of tick-free goats with a pharmacokinetic characterization of eprinomectin (topically administered at 0.5, 1.0 and 1.5mg/kg) and ivermectin (subcutaneous treatment given at (0.2 and 0.4mg/kg) in goats. Heparinized blood samples were taken between 0 and 21 days post-treatment. Higher and more persistent drug plasma concentrations were recovered after the subcutaneous treatment with ivermectin compared to those obtained for eprinomectin topically administered. The understanding of the relationship among the pattern of drug absorption, the kinetic disposition and the resultant clinical efficacy is relevant to improve the poor performance observed for ivermectin and eprinomectin against A. parvum on goats.

Composición química y aplicaciones clínicas del aceite de oliva extra virgen

La composición química del aceite de oliva extra virgen (AOEV) se compone principalmente de triglicéridos, ácidos grasos insaturados como ácido oleico, ácido linoleico y el α-linolénico. También se destacan compuestos fenólicos de tres clases químicas: simples, secoiridoides y lignanos. En la presente revisión se analizó el consumo del AOEV en enfermedades crónicas, ciertos tipos de cáncer y en enfermedades neurodegenerativas. La evidencia muestra que el consumo de entre 8 y 40 g de AOEV diario tiene efectos protectores en enfermedades cardiovasculares, puede evitar la aparición de diabetes tipo 2 y aumentar los niveles de colesterol HDL. Respecto al cáncer, entre los efectos evaluados se destacan los encontrados a partir de los compuestos fenólicos hidroxitirosol (HT) y oleocantal, los que han demostrado un efecto protector en algunos tipos de cáncer como cáncer de piel y de mama. En las enfermedades neurodegenerativas, se observó que el consumo diario de 50 g de AOEV, tiene un efecto inhibidor en la degeneración neuronal atribuido a sus compuestos fenólicos como oleuropeina e HT. Investigaciones a futuro debieran enfocarse en determinar los efectos a largo plazo del consumo de AOEV en las diferentes enfermedades analizadas, para así poder ir estableciendo la "dosis" de AOEV que permita obtener resultados protectores sobre la salud. Además de explorar los efectos de las diferentes variedades de aceitunas (con sus componentes bioactivos particulares) con el fin de establecer los efectos en la salud y enfermedad asociados a variedades específicas.

The chemical composition of extra virgin olive oil (EVOO) is mainly composed of triglycerides, unsaturated fatty acids such as oleic acid, linoleic acid, and α-linolenic acid. Phenolic compounds of three chemical classes are also relevant, such as simple, secoiridoids, and lignans. Here, we review the association between EVOO consumption and chronic diseases, certain types of cancer, and neurodegenerative diseases. Evidence shows that consuming between 8 and 40 g of EVOO / day has protective effects on cardiovascular diseases, can prevent the onset of type 2 diabetes, and increases HDL cholesterol levels. Regarding cancer, phenolic compounds hydroxytyrosol (HT) and oleocanthal have protective effects on some types of cancer, such as skin and breast cancer. Regarding neurodegenerative diseases, daily consumption of phenolic compounds such as oleuperin and hydroxytyrosol and 50 g of EVOO has an inhibitory effect on neuronal degeneration and a protective effect on neuroprotective capacity. Future research should focus on determining the long-term impact of EVOO consumption on different diseases to establish the "dose" of EVOO that will allow health-protective results. It is also necessary to establish the effects of the specific olives (with their particular bioactive components) to establish the different impacts on health and disease associated with olives varieties.

A tropical bay as a reference area defined by multiple lines of evidences.

References areas are sites that have undergone little or no anthropogenic impact and therefore represent the natural state of an environment. The objective of this study was to test if the Camamu Bay (CB), Bahia, can be used as a reference area for tropical coastal environments. Trace and major elements, polycyclic aromatic hydrocarbons (PAH), and the structure of the benthic macrofauna were determined. To compare the studied sites and identify the possible occurrence of anomalous concentrations, trace elements were normalized by Al and linear regressions were also performed. For all trace elements (except Cu), regressions showed a significant correlation (p<0.05) and few outliers (<3% of cases), showing that the concentrations found represent natural values for this bay. In the case of Cu, the highest concentrations were found near small municipalities, which may be associated with domestic sewage. About 60% of the organic compounds occurred at levels below the limit of quantification (<0.26ngg-1). The sum of PAHs was low for all stations, ranging from 1.17 to 313ngg-1. The benthic assemblages also indicated that the CB is a healthy, well-preserved ecosystem that deserves conservation efforts. The integrated use of geochemical and biotic data supported the use of CB as a reference area. Capsule: Organic and inorganic contaminants together with macrobenthic assemblages indicated that Camamu Bay is a pristine, tropical reference area.

Efficient feature selection for neural network based detection of flaws in steel welded joints using ultrasound testing.

This work studies methods for efficient extraction and selection of features in the context of a decision support system based on neural networks. The data comes from ultrasonic testing of steel welded joints, in which are found three types of flaws. The discrete Fourier, wavelet and cosine transforms are applied for feature extraction. Statistical techniques such as principal component analysis and the Wilcoxon-Mann-Whitney test are used for optimal feature selection. Two different artificial neural network architectures are used for automatic classification. Through the proposed approach, it is achieved a high discrimination efficiency by using only 20 features to feed the classifier, instead of the original 2500 A-scan sample points.

Molecular mechanisms mediating gastrin-releasing peptide receptor modulation of memory consolidation in the hippocampus.

Although the gastrin-releasing peptide-preferring bombesin receptor (GRPR) has been implicated in memory formation, the underlying molecular events are poorly understood. In the present study, we examined interactions between the GRPR and cellular signaling pathways in influencing memory consolidation in the hippocampus. Male Wistar rats received bilateral infusions of bombesin (BB) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. Intermediate doses of BB enhanced, whereas a higher dose impaired, 24-h IA memory retention. The BB-induced memory enhancement was prevented by pretraining infusions of a GRPR antagonist or inhibitors of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) kinase and protein kinase A (PKA), but not by a neuromedin B receptor (NMBR) antagonist. We next further investigated the interactions between the GRPR and the PKA pathway. BB-induced enhancement of consolidation was potentiated by coinfusion of activators of the dopamine D1/D5 receptor (D1R)/cAMP/PKA pathway and prevented by a PKA inhibitor. We conclude that memory modulation by hippocampal GRPRs is mediated by the PKC, MAPK, and PKA pathways. Furthermore, pretraining infusion of BB prevented beta-amyloid peptide (25-35)-induced memory impairment, supporting the view that the GRPR is a target for the development of cognitive enhancers for dementia.

GH response to hypoglycemia and clonidine in the GH-releasing hormone resistance syndrome.

GH secretion by the pituitary is the result of the balance between the stimulatory effect of GHRH and the inhibitory effect of SS. Patients with mutations in GHRH receptor (GHRH-R) gene (GHRH-R) offer a unique model to study the mechanism of action of different GH secretion stimuli. In the past, we have demonstrated a small but significant GH response to a GH secretagogue (GHRP-2) in a homogenous cohort of patients with severe GH deficiency (GHD) due to a homozygous null mutation in GHRH-R (IVS1+1G-->A). Now, we sought to determine if we could detect a GH response to hypoglycemia (ITT: insulin tolerance test) or clonidine (CL) in these patients. Nine young GHD subjects underwent both ITT and CL tests, and 2 additional subjects underwent only CL test. There was a small but significant GH increase during ITT, but not during CL test. These results indicate that a minimal albeit significant GH response to ITT can occur despite complete lack of GHRH-R function.