A recombinant chimeric protein composed of human and mice-specific CD4+ and CD8+ T-cell epitopes protects against visceral leishmaniasis.

In this study, a recombinant chimeric protein (RCP), which was composed of specific CD4+ and CD8+ T-cell epitopes to murine and human haplotypes, was evaluated as an immunogen against Leishmania infantum infection in a murine model. BALB/c mice received saline were immunized with saponin or with RCP with or without an adjuvant. The results showed that RCP/saponin-vaccinated mice presented significantly higher levels of antileishmanial IFN-γ, IL-12 and GM-CSF before and after challenge, which were associated with the reduction of IL-4 and IL-10 mediated responses. These animals showed significant reductions in the parasite burden in all evaluated organs, when both limiting dilution and quantitative real-time PCR techniques were used. In addition, the protected animals presented higher levels of parasite-specific nitrite, as well as the presence of anti-Leishmania IgG2a isotype antibodies. In conclusion, the RCP/saponin vaccine could be considered as a prophylactic alternative to prevent against VL.

Decoration of trastuzumab with short oligonucleotides: synthesis and detailed characterization.

Trastuzumab (Herceptin®) is an FDA-approved therapeutic antibody currently employed in the treatment of metastatic stages of breast cancer. Herein, we propose a simple, fast and cost-effective methodology to conjugate trastuzumab with 22-mer 5' thiol-modified oligonucleotides using a bifunctional crosslinker. The conjugates were successfully characterized by MALDI-ToF MS and SDS-PAGE, obviating the need for enzymatic digestion and difficult chromatographic separations. Furthermore, ELISA was performed to ensure that trastuzumab activity is not affected by oligonucleotide conjugation.

X-ray powder diffraction at the XRD1 beamline at LNLS.

Various upgrades have been completed at the XRD1 beamline at the Brazilian synchrotron light source (LNLS). The upgrades are comprehensive, with changes to both hardware and software, now allowing users of the beamline to conduct X-ray powder diffraction experiments with faster data acquisition times and improved quality. The main beamline parameters and the results obtained for different standards are presented, showing the beamline ability of performing high-quality experiments in transmission geometry. XRD1 operates in the 5.5-14 keV range and has a photon flux of 7.8 × 109 photons s-1 (with 100 mA) at 12 keV, which is one of the typical working energies. At 8 keV (the other typical working energy) the photon flux at the sample position is 3.4 × 1010 photons s-1 and the energy resolution ΔE/E = 3 × 10-4.

High intake of heterocyclic amines from meat is associated with oxidative stress.

High meat intake has been related to chronic diseases such as cancer and CVD. One hypothesis is that heterocyclic amines (HCA), which are formed during the cooking process of meat, can generate reactive species. These compounds can cause oxidation of lipids, proteins and DNA, resulting in oxidative stress, cell damage and loss of biological function. This association has been seen in vitro; however, it remains unclear in vivo. The aim of the present study was to investigate the association between oxidative stress and HCA intake, and oxidative stress and meat intake. Data were from the Health Survey for Sao Paulo--ISA-Capital (561 adult and elderly). Food intake was estimated by one 24-h dietary recall (24HR) complemented by a detailed FFQ with preferences of cooking methods and level of doneness for meat. HCA intake was estimated linking the meat from the 24HR to a database of HCA. Oxidative stress was estimated by malondialdehyde (MDA) concentration in the plasma, after derivatisation with thiobarbituric acid and quantification by HPLC/diode array. Analyses were performed using multivariate logistic regressions adjusted for smoking, sex, age, BMI, skin colour, energy intake, fruit and vegetable intake, and physical activity. A positive association between HCA intake and MDA concentration (OR 1·17; 95% CI 1·01, 1·38) was observed, showing that HCA from meat may contribute to increase oxidative stress, and may consequently increase the risk of chronic diseases.

Fatty acids profiles of some Spanish wild vegetables.

Polyunsaturated fatty acids play an important role in human nutrition, being associated with several health benefits. The analyzed vegetables, in spite of its low fat content, lower than 2%, present a high proportion of polyunsaturated fatty acids of n-3, n-6 and n-9 series, such as α-linolenic, linoleic and oleic acids, respectively. Wild edible plants contain in general a good balance of n-6 and n-3 fatty acids. The present study tries to contribute to the preservation and valorization of traditional food resources, studying the fatty acids profile of 20 wild vegetables by gas-liquid chromatography with flame ionization detection. Results show that species in which leaves are predominant in their edible parts have in general the highest polyunsaturated fatty acid/saturated fatty acid ratios: Rumex pulcher (5.44), Cichorium intybus (5.14) and Papaver rhoeas (5.00). Due to the low n-6/n-3 ratios of the majority of the samples, they can be considered interesting sources of n-3 fatty acids, especially those with higher total fat amount, such as Bryonia dioica, Chondrilla juncea or Montia fontana, with the highest contents of α-linolenic acid (67.78, 56.27 and 47.65%, respectively). The wild asparaguses of Asparagus acutifolius and Tamus communis stand out for their linoleic acid content (42.29 and 42.45%, respectively). All these features reinforce the interest of including wild plants in diet, as an alternative to the variety of vegetables normally used.

Eggs of tegu lizard, Salvator merianae (Duméril & Bilbron, 1839) (Squamata; Teiidae) damaged by fungal infections.

The tegu (Salvator merianae) is the largest lizard found in Brazil and has a wide distribution, occurring in several biomes. The presence of fungi on reptilian eggs initially occurs on infertile eggs, which leads to a subsequent infection in fertile eggs, causing damage and death of embryos. The objective of this study was to identify the fungi that caused lesions in the eggs of tegu in captivity. Swabs were collected on infected and healthy eggshells, in an embryo that died and the substrate of the incubation box. Samples were submitted to saboraund dextrose agar. A total of 93.3% of positive samples were obtained for the fungi Fusarium (11/14), Trichoderma (1/15), Penicilium (1/15), Mucor (1/15), and yeasts of the genus Trichosporon. Therefore, Fusarium was the main agent that caused the lesion and death of embryos in the eggs of the tegu lizard. Sanitary control methods may be taken to avoid fungal infections in the eggs.

Involvement of monoaminergic targets in the antidepressant- and anxiolytic-like effects of the synthetic alkamide riparin IV: Elucidation of further mechanisms through pharmacological, neurochemistry and computational approaches.

Despite recent advances, current antidepressants have considerable limitations: late onset of action and the high profile of refractoriness. Biomedical research with natural products has gained growing interest in the last years, and had provide useful candidates for new antidepressants. Riparins are a group of natural alkamides obtained from Aniba riparia, which had marked neuroactive effects, mainly as antidepressant and antinociceptive agents. We made modifications of the basic structure of riparins, originating a synthetic alkamide, also known as riparin IV (RipIV). RipIV demonstrated a superior analgesic effect than its congeners and a marked antidepressant-like effect. However, the basic mechanism for the central effects of RipIV remains unknown. Here, we aimed to investigate the participation of monoaminergic neurotransmission targets in the antidepressant-like effects of RipIV. To do this, we applied a combined approach of experimental (classical pharmacology and neurochemistry) and computer-aided techniques. Our results demonstrated that RipIV presented antidepressant- and anxiolytic-like effects without modifying locomotion and motor coordination of mice. Also, RipIV increased brain monoamines and their metabolite levels. At the higher dose (100 mg/kg), RipIV increased serotonin concentrations in all studied brain areas, while at the lower one (50 mg/kg), it increased mainly dopamine and noradrenaline levels. When tested with selective receptor antagonists, RipIV antidepressant effect showed dependence of the activation of multiple targets, including D1 and D2 dopamine receptors, 5-HT2A/2, 5-HT3 receptors and α2 adrenergic receptors. Molecular docking demonstrated favorable binding conformation and affinity of RipIV to monoamine oxidase B (MAO-B), serotonin transporter (SERT), α1 receptor, D2 receptor, dopamine transporter (DAT) and at some extent GABA-A receptor. RipIV also presented a computationally predicted favorable pharmacokinetic profile. Therefore, this study demonstrated the involvement of monoaminergic targets in the mechanism of RipIV antidepressant-like action, and provide evidence of it as a promising new antidepressant.

Giant Barocaloric Effects in Natural Rubber: A Relevant Step toward Solid-State Cooling.

Solid-state cooling based on i-caloric effects has shown to be a promising alternative to the conventional refrigeration devices. Only very recently, the research on barocaloric materials is receiving a deal of attention due to the demonstration of giant barocaloric effects in shape-memory alloys. Regarding polymers, there is still a lack of literature, despite their high caloric potential. Thus, we present here giant barocaloric effects in natural rubber, a low-cost and environmental friendly elastomer polymer. The maximum values of entropy and temperature changes are larger than those previously reported for any promising barocaloric material. Moreover, the huge normalized temperature change and refrigerant capacity exhibited by natural rubber confirm its high potential for cooling applications. We also verify a relevant dependence of the barocaloric effect on the glass transition in natural rubber. Our findings suggest that commercial refrigeration devices based on barocaloric effects from elastomer polymers can be envisaged in the near future.

Note: Experimental setup for measuring the barocaloric effect in polymers: Application to natural rubber.

Barocaloric materials have shown to be promising alternatives to the conventional vapor-compression refrigeration technologies. Nevertheless, barocaloric effect (σb-CE) has not been extensively examined for many classes of materials up to now. Aiming at fulfilling this gap, the present paper describes the development of a high-pressure experimental setup for measuring the σb-CE in polymers. The design allows simultaneous measurements of temperature, pressure, and strain during the barocaloric cycle. The system proved to be fully functional through basic experiments using natural rubber. Samples exhibited large temperature variations associated with the σb-CE. Strain-temperature curves were also obtained, which could allow indirect measurements of the isothermal entropy change.

Chemical disorder determines the deviation of the Slater-Pauling rule for Fe2MnSi-based Heusler alloys: evidences from neutron diffraction and density functional theory.

Fe2MnSi fails to follow the Slater-Pauling rule. This phenomenon is thought to originate from either: (i) an antiferromagnetic arrangement of Mn ions at low temperature and/or (ii) chemical disorder. An important insight on this issue could be achieved by considering Fe2MnSi1-x Ga x compounds, thoroughly studied here by means of magnetization, neutron diffraction and density functional calculations (DFT). Our results indicate that chemical disorder (and not the antiferromagnetic arrangement) is responsible for the deviation of the Slater-Pauling rule on Fe2MnSi-based Heusler alloys. Furthermore, evidences suggest that Ga substitution into Si site favors the Fe/Mn disorder, further enhancing the observed deviation.

First occurrence of Arnold Chiari type II malformation and associated abnormalities in a Gir calf produced in vitro from Brazil - case report / [Primeira ocorrência de malformação de Arnold Chiari tipo II e anormalidades associadas em uma bezerra Gir de produção in vitro no Brasil - relato de caso]

This study characterized the clinical, radiological, ultrasound, and necroscopic findings of a case of Arnold-Chiari type II malformation in a Gir breed calf from Brazil. The animal was hospitalized at sixty days of age, in permanent sternal recumbency, cutaneous appendix at the 4th lumbar vertebra and kyphoscoliosis of the caudal and lumbosacral thoracic spine. Radiographic examination of the spine and skull revealed spina bifida and suspected occipital hypoplasia. Upon examination of myelography with an injection of lumbar and atlantooccipital contrast, it was possible to visualize the meningocele at the 4th lumbar vertebra region and findings at the rhombencephalon level of increased regional pressure with failure to fill the contrast in the posterior fossa, in the presence of clear demarcation of the circumvolutions of the cerebral cortex and the subarachnoid space of the cervical spinal cord. Ultrasonographic examination of the cerebellum showed an insinuation of the cerebellar worm through the foramen magnum. The animal did not show changes in complete blood count, biochemical series, and cerebrospinal fluid and was negative for Pestivirus. There was a worsening of the clinical conditions and the animal died. This malformation of unknown etiology must be studied as a differential diagnosis of the nervous system disorders.(AU)

Este estudo caracterizou os achados clínicos, radiológicos, ultrassonográficos e necroscópicos de um caso de malformação de Arnold-Chiari tipo II em uma bezerra Gir no Brasil. O animal foi hospilatizado aos 60 dias de idade, apresentando decúbito esternal permanente, apêndice cutâneo na altura da quarta vértebra lombar e cifoescoliose da coluna vertebral torácica caudal e lombossacra. Ao exame radiográfico da coluna e do crânio, foram observadas espinha bífida e suspeita de hipoplasia occipital. Ao exame de mielografia com injeção de contraste lombar e atlanto-occipital, foi possivel visualizar a meningocele na altura da quarta vértebra lombar e achados em nível rombencefálico de aumento da pressão regional com falha de preenchimento do contraste na fossa posterior, na presença de nítida demarcação das circunvoluções do córtex cerebral e do espaço subaracnoide da medula espinhal cervical. Ao exame ultrassonográfico do cerebelo, foi observada insinuação do verme cerebelar através do forame magno. O animal não apresentou alterações em hemograma completo, série bioquímica e fluido cérebro-espinhal e foi negativo para Pestivirus. Houve uma piora do quadro clínico e o animal morreu. Essa malformação de etiologia desconhecida deve ser estudada como um diagnóstico diferencial.(AU)

Hepatocellular carcinoma: incidental finding in cirrhotic explanted livers.

INTRODUCTION: Cirrhosis predisposes to the development of hepatocellular carcinoma (HCC), demanding that these patients undergo follow-up with imaging methods for the early detection of neoplastic nodules. Morphologic study of the explanted livers allows identification of lesions not detected pre-operatively. OBJECTIVE: To assess the frequency and to characterize the HCC found incidentally at pathological evaluation of explanted cirrhotic livers. MATERIAL AND METHODS: Thirty patients had HCC diagnosed in explanted cirrhotic livers. The livers were sectioned at intervals of 0.5 cm. Each detached nodule was selected for microscopic study according to size, color and/or consistency. Retrospective analysis of the clinical records was performed comparing available data from various imaging methods. RESULTS: In 11 patients, 16 HCC had previously been identified in the explants by one or more imaging methods. In the other 19 explanted livers (63.3%), HCC was incidentally found. All HCC identified in 9 patients and some of them in 10 patients were incidentally found, varying from microscopic focuses to 2 cm diameter lesions. They varied from only one (5 cases) to multiple nodules (7 cases). DISCUSSION: Imaging methods may underestimate the number of HCC in cirrhotic livers. Histological study is an essential tool that can early detect tumor nodules not previously detected by imaging methods. In our study, although small, multicentric HCC were identified, illustrating the multifocal nature of the hepatic carcinogenesis. Future studies must correlate these findings with patient outcomes. CONCLUSION: Characterization of explanted cirrhotic livers for HCC is important for previously known and incidentally found lesions.

Eggs of tegu lizard, Salvator merianae (Duméril & Bilbron, 1839) (Squamata; Teiidae) damaged by fungal infections / Ovos de lagarto tegu, Salvator merianae (Duméril e Bilbron, 1839) (Squamata; Teiidae) danificados por infecções fúngicas

Abstract The tegu (Salvator merianae) is the largest lizard found in Brazil and has a wide distribution, occurring in several biomes. The presence of fungi on reptilian eggs initially occurs on infertile eggs, which leads to a subsequent infection in fertile eggs, causing damage and death of embryos. The objective of this study was to identify the fungi that caused lesions in the eggs of tegu in captivity. Swabs were collected on infected and healthy eggshells, in an embryo that died and the substrate of the incubation box. Samples were submitted to saboraund dextrose agar. A total of 93.3% of positive samples were obtained for the fungi Fusarium (11/14), Trichoderma (1/15), Penicilium (1/15), Mucor (1/15), and yeasts of the genus Trichosporon. Therefore, Fusarium was the main agent that caused the lesion and death of embryos in the eggs of the tegu lizard. Sanitary control methods may be taken to avoid fungal infections in the eggs.

Resumo O teiú (Salvator merianae) é o maior lagarto encontrado no Brasil e possui ampla distribuição, sendo encontrado em vários biomas. A presença de fungos em ovos de répteis ocorre inicialmente em ovos inférteis, o que leva à uma infecção posterior em ovos férteis, gerando danos e morte dos embriões. O objetivo deste estudo foi o de identificar os fungos geradores de lesões em ovos de teiú em cativeiro. Foram coletados suabes na casca de ovos infectados e sadios, além de um embrião que veio a óbito, e do substrato presente na caixa de incubação. As amostras foram submetidas ao cultivo em ágar Saboraund dextrose. Um total de 93,3% de amostras foram positivas para os fungos Fusarium (11/15), Trichoderma (1/15), Penicillium (1/15), Mucor (1/15) e leveduras do gênero Trichosporon (3/15). Logo, Fusarium foi o principal agente causador das lesões e morte de embriões nos ovos do lagarto teiú. Métodos de controle sanitário podem ser adotados para evitar infecção fúngicas nos ovos.

Transplacental Transmission of Ovine Herpesvirus 2 in Cattle with Sheep-associated Malignant Catarrhal Fever.

Sheep-associated malignant catarrhal fever (SA-MCF) is an important infectious disease of ruminants worldwide that is caused by ovine herpesvirus 2 (OvHV-2). OvHV-2 is transmitted predominantly by contact between infected and susceptible hosts, while the documentation of vertical transmission is rare. This report presents the pathological and molecular findings associated with transplacental transmission of OvHV-2 in cattle. Two Girolanda cows with corneal oedema, lethargy, mucopurulent nasal discharge and ulcerative stomatitis died spontaneously; one of these was pregnant with a 4-month-old fetus. Significant pathological findings included widespread lymphoplasmacytic necrotizing vasculitis and lymphoplasmacytic accumulations in several organs of both cows and the fetus. A polymerase chain reaction that targeted the tegument protein gene of OvHV-2 amplified viral DNA from the brain of the pregnant cow and her fetus, as well as from the kidney of the pregnant cow. The pathological findings observed in the cow and her fetus, together with the presence of OvHV-2 DNA in tissues of these animals, are suggestive of transplacental transmission of OvHV-2 in SA-MCF in cattle.

Antinociceptive property of new 4-acyl-arylhydrazone pyrazole compounds.

A series of new 4-acyl-arylhydrazone pyrazole compounds were tested for antinociceptive activity using the inhibition of abdominal contortions induced by acetylcholine (4 mg/kg, ip) in the mouse. Dipyrone was used for comparison of the antinociceptive potency of the compounds being tested. All drugs were administered po in saline (dipyrone) or in propylene glycol (4-acyl-arylhydrazones). The maximum response induced by dipyrone (86% inhibition) was assigned an efficacy index of 1.0. Although none of the compounds had an efficacy index greater than 1.0, all three reached 1.0. The two most potent compounds, W1d and W1g, which also had an efficacy similar to that of dipyrone, contain a p-N(CH3)2 and m-OH,p-OCH3 group in the aromatic ring of the acyl-hydrazone, respectively. W1d presented the lowest antinociceptive ED50 in the series (1.41 mg/kg) and was eleven times more potent than dipyrone (ED50 = 15.80 mg/kg). Other substitutions at the para position had lower potency than W1d. The present results indicate that the introduction of a group at the para position of the acyl-arylhydrazone ring increases the antinociceptive activity of these compounds to provide compounds of the same efficacy but greater potency than dipyrone to which these new compounds are structurally related. Other assays of nociceptive activity are being used to characterize the mechanism of action of the potential new drugs.

CADEIA and REJECT. Codes to compute relevant gamma-gamma and gamma-X true-coincidence lines in absolute counting of gamma rays with a LEPD.

CADEIA and REJECT are computer codes for generating gamma-gamma and gamma-X true-coincidence lines for calculation of correction factors for absolute counting of gamma rays in a low energy photon detector. They are written in FORTRAN 77. True-coincidence lines are generated by CADEIA; they are submitted to selection by REJECT according to the rejection criteria defined by L. Moens et al. and F. De Corte. Final relevant lines for true-coincidence correction factors are given as output of REJECT.

Effect of chronic ritonavir administration on pregnant rats and their fetuses.

In view of the very important role played by ritonavir in the prevention of maternal-fetal HIV-vertical transmission, the aim of this experimental study was to evaluate its possible effects on several important obstetric parameters. Ritonavir was administered daily to three groups of pregnant rats (E1 = 20 mg/kg; E2 = 60 mg/kg; E3 = 180 mg/kg; n = 10 in every group) from 'zero' up to the 20th day of pregnancy. Controls (n = 10) were injected with the drug vehicle (propyleneglycol) in the same schedule. We evaluated the effects on fetal and maternal weight gain, placental weight, number of implantations and resorptions, malformations, fertility rate, and maternal and fetal death rates. Body weight gain of the E3 group was significantly lower than that of the other groups, most likely due to a toxic effect of the highest dose of ritonavir. Ritonavir did not affect the number of implantations. Group E3 had five resorptions and some reduction in fertility. The mortality rate was significantly affected by ritonavir (2/10 maternal deaths in E2 and 4/10 in E3). On the other hand, no alterations were observed in the fetuses, a finding which could be due at least in part to the protective action of placental P-glycoprotein.

Possible analgesic effect of vigabatrin in animal experimental chronic neuropathic pain.

Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constrictive sciatic neuropathy was induced (Bennet & Xie model). For testing pain symptoms, spontaneous (scratching) and evoked behaviors to noxious (46 degrees C) and non-noxious (40 degrees C) thermal stimuli were quantified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA) on experimental neuropathic pain, as shown by the significant (p < 0.05) decreasing effect of vigabatrin on scratching and by its significant (p < 0.05) increasing effect on the latency of the right hindpaw withdrawal of the animals to noxious thermal stimulus. This was corroborated by similar findings with analgesic anticonvulsants (carbamazepine, phenytoin and valproic acid). This possible and not yet described analgesic effect of vigabatrin seems not to be opioid mediated.

[Prevalence of biliary lithiasis in cirrhotics: necropsy evaluation]. / Prevalência de litíase biliar em cirróticos: avaliação necroscópica.

In order to investigate a possible association between hepatic cirrhosis and biliary lithiasis, an analysis on 3,332 necropsy report diagnosis was carried out. Gallstones were present in 19.5% of 123 cirrhotics and in 4.9% of 3,209 non-cirrhotics patients. We concluded that lithiasis is significantly more frequent in cirrhotics than in non-cirrhotics. Chronic hemolysis, slow emptying of the gallbladder, and defective bile acidification by the gallbladder would explain such association. The male-to-female ratio of lithiasis occurrence was 2.08:1 in the cirrhotic group and 2.4:1 among the non-cirrhotics. This difference was not significant. Pigmentary gallstones were commoner among cirrhotics and significantly more frequent in cirrhotics than in non-cirrhotics. This would be explained by chronic hemolysis and by bilirubin conjugation defects. Lithiasis was more frequent in secondary biliary cirrhosis, followed by postnecrotic cirrhosis of viral etiology.

[Psychology in national nursing scientific publications]. / A psicologia na produção científica nacional de enfermagem.

This study aimed, through a review of Nursing periodicals, at identifying elements of interaction between Nursing and Psychology. Authors selected 317 articles that met the criterion of approaching psychological issues. The analysis included: 1. the focussed theme; 2. authors' position; 3. references to Psychology works; 4. Psychology's theoretical frameworks and 5. methodology. Authors concluded that this interaction is occurring through a theoretical-methodological dialogue. The contacts among professionals with different academic backgrounds were scarce.