Development of inhaled moxifloxacin-metformin formulation as an alternative for pulmonary tuberculosis treatment.

Resistant M. tuberculosis strains threaten pulmonary tuberculosis (P-TB) control since they limit drug options. Drug repositioning and new development strategies are urgently required to overcome resistance. Studies have already shown the beneficial role of the oral antidiabetic metformin as an anti-tuberculosis adjuvant drug. This work aimed to develop an inhalatory dry powder co-formulation of metformin and moxifloxacin to figure out a future option for P-TB treatment. Pre-formulation evaluations indicated the physicochemical compatibility of constituents, demonstrating powder crystallinity and acceptable drug content. Eight moxifloxacin-metformin dry powder formulations were produced by spray drying, and solid-state characterizations showed partial amorphization, ascribed to moxifloxacin. Four formulations containing L-leucine exhibited micromeritic and in vitro deposition profiles indicating pulmonary delivery suitability, like spherical and corrugated particle surface, geometric diameters < 5 µm, high emitted doses (>85 %), and mass median aerodynamic diameters between 1-5 µm. The use of a second spray dryer model further optimized the aerodynamic properties and yield of the best formulation, demonstrating the influence of the equipment used on the product obtained. Moreover, the final formulation showed high in vitro cell tolerability and characteristics in permeability studies indicative of good drug retention in the lungs.

Impact of Resin Composite Viscosity and Fill-technique on Internal Gap in Class I Restorations: An OCT Evaluation.

The aim of this in vitro study was to quantitatively evaluate the internal gap of resin composites of high-and low-viscosity used in single- and incremental-fill techniques in Class I cavities exposed to thermal cycling (TC) using optical coherence tomography (OCT). Cavities of 4-mm depth and 3-mm diameter were prepared in 36 third molars randomly distributed into four groups, according to viscosity of restorative resin-based composite (high or low viscosity, all from 3M Oral Care) and technique application (bulk or incremental fill) used (n=9): RC, high-viscosity, incremental-fill, resin-based composite (Filtek Z350 XT Universal Restorative); BF, high-viscosity, bulk-fill, resin-based composite (Filtek One Bulk Fill); LRC, lowviscosity, incremental-fill, resin-based composite (Filtek Z350 XT Flowable Universal Restorative); and LBF, low-viscosity, bulk-fill, resin-based composite (Filtek Flowable Restorative). Single Bond Universal Adhesive system (3M Oral Care) was used in all the experimental groups. The incremental-fill technique was used for RC and LRC groups (2-mm increments), and a single-layer technique was used for BF and LBF groups, as recommended by the manufacturer. The internal adaptation of the resin at all dentin walls was evaluated before and after TC (5000 cycles between 5°C and 55°C) using OCT images. Five images of each restored tooth were obtained. Images were analyzed using ImageJ software that measured the entire length of the gaps at the dentin-restoration interface. The length of gaps (µm) was analyzed using two-way repeated measures ANOVA and the Tukey tests (α=0.05). There was a significant interaction between material types and TC (p=0.006), and a significant difference among all material types (p<0.0001), before and after TC (p<0.0001). Increased internal gaps at the dentin-restoration interface were noticed after TC for all groups. RC presented the lowest value of internal gap before and after TC, while LBF showed the highest values of internal gap after TC. In conclusion, TC negatively affected the integrity of internal gap, whereas high-viscosity, incremental-fill, resin-based composite presented better performance in terms of internal adaptation than low-viscosity, bulk-fill materials in Class I cavities.

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)

Multicentric chondrosarcoma involving the appendicular skeleton: a case report and literature review.

Chondrosarcomas constitute the 3rd most common primary bone malignancy. These tumours grow slowly and rarely metastasize, usually having a good prognosis after surgery. Among patients registered and treated at the Brazilian National Institute of Traumatology and Orthopedics, an uncommon case of chondrosarcoma was identified in a 63-year-old man, who was diagnosed with multicentric chondrosarcoma of the appendicular skeleton. This example is atypical in the medical literature because multicentric tumours are different from metastatic events, and their frequency in chondrosarcoma is rare. This article therefore provides a rare case report alongside a review of additional cases in the medical literature.

Weight adjustment equation for hair sheep raised in warm conditions.

To estimate the nutritional requirements of hair sheep, knowledge about the animal's weight and its relationships with growth performances is essential. A study was carried with the objective to establish the relationships between BW, fasting BW (FBW), empty BW (EBW), average daily gain (ADG) and empty BW gain (EBWG) for hair sheep in growing and finishing phases in Brazilian conditions. Databases were obtained from 32 studies, for a total of 1145 observations; there were 3 sex classes (non-castrated male, castrated male and female) and 2 feeding systems (pasture and feedlot). The most representative breeds in the database were Santa Ines (n = 473), Morada Nova (n = 70) and Brazilian Somali (n = 47). The other animals in the database were crossbreeds (n = 555). The FBW (kg), EBW and EBWG (kg/day) were estimated according to linear regression. A random coefficient model was adopted, considering the study as a random effect and including the possibility of covariance between the slope and the intercept. The coefficients obtained from the linear regression of the FBW against the BW, EBW against the FBW and EBWG against the ADG did not differ between sex class (P > 0.05) and genotype (P > 0.05). The equations generated to estimate FBW from the BW, EBW from the FBW and EBWG from the ADG are as follows: FBW = -0.5470 (±0.2025) + 0.9313(±0.019) × BW, EBW = -1.4944 (±0.3639) + 0.8816 (±0.018) × FBW and EBWG = 0.906 (±0.019) × ADG, respectively. The low mean squared error values found in the cross-validation confirmed the reliability of these equations. Considering a sheep with a BW of 30 kg and a 100 g ADG, the estimated FBW, EBW and EBWG calculated using the generated equations are 27, 22.65 and 0.090 kg, respectively. In conclusion, the generated equations can be used in growing hair sheep. The validation procedure applied to the generated equations showed that its use for hair sheep seems to be appropriate.

Tailoring the physical and chemical properties of Sn1-xCoxO2 nanoparticles: an experimental and theoretical approach.

In this work, we present a coupled experimental and theoretical first-principles investigation on one of the more promising oxide-diluted magnetic semiconductors, the Sn1-xCoxO2 nanoparticle system, in order to see the effect of cobalt doping on the physical and chemical properties. Our findings suggest that progressive surface enrichment with dopant ions plays an essential role in the monotonous quenching of the surface disorder modes. That weakening is associated with the passivation of the oxygen vacancies as the Co excess at the surface becomes larger. Room-temperature 119Sn Mössbauer spectroscopy data analysis revealed the occurrence of a distribution of isomer shifts, related to the different non-equivalent surroundings of Sn4+ ions and the coexistence of Sn2+/Sn4+ at the particle surfaces provoked by the inhomogeneous distribution of Co ions, in agreement with the X-ray photoelectron spectroscopy measurements. Magnetic measurements revealed a paramagnetic behavior of the Co ions dispersed in the rutile-type matrix with antiferromagnetic correlations, which become stronger as the Co content is increased. Theoretical calculations show that a defect with two Co mediated by a nearby oxygen vacancy is the most likely defect. The predicted effects of this defect complex are in accordance with the experimental results.

The Centre for Data and Knowledge Integration for Health (CIDACS): Linking Health and Social Data in Brazil.

The Centre for Data and Knowledge Integration for Health (CIDACS) was created in 2016 in Salvador, Bahia-Brazil with the objective of integrating data and knowledge aiming to answer scientific questions related to the health of the Brazilian population. This article details our experiences in the establishment and operations of CIDACS, as well as efforts made to obtain high-quality linked data while adhering to security, ethical use and privacy issues. Every effort has been made to conduct operations while implementing appropriate structures, procedures, processes and controls over the original and integrated databases in order to provide adequate datasets to answer relevant research questions. Looking forward, CIDACS is expected to be an important resource for researchers and policymakers interested in enhancing the evidence base pertaining to different aspects of health, in particular when investigating, from a nation-wide perspective, the role of social determinants of health and the effects of social and environmental policies on different health outcomes.

Síndrome de Eisenmenger em um gato / Eisenmenger syndrome in cat

A 6-month-old female, 1.0kg, uncastrated female Persian cat was brought to the Veterinary Hospital at State University of Ceara, with a history of dyspnea, prostration, hyporexia and progressive weight loss for a month. On physical examination, systolic cardiac murmur, cyanosis and dyspnea were detected. Unfortunately, the cat died during oxygen therapy. Necropsy examination revealed an increase in cardiac silhouette and ventricular septal defect of 2cm in diameter. Macroscopically the lungs were collapsed, with absent and diffusely reddish blackish crepitus, and the liver with blackish red coalescent multifocal areas, interspersed with lighter areas and lobular pattern with irregular brownish multifocal areas intercepted by brownish areas. Thus, the necropsy results together with the history and physical examination of the animal confirmed the diagnosis of Eisenmenger Syndrome, becoming the report of the first case, in a cat, in Brazil.(AU)

Síndrome de Eisenmenger em um gato / Eisenmenger syndrome in cat

A 6-month-old female, 1.0kg, uncastrated female Persian cat was brought to the Veterinary Hospital at State University of Ceara, with a history of dyspnea, prostration, hyporexia and progressive weight loss for a month. On physical examination, systolic cardiac murmur, cyanosis and dyspnea were detected. Unfortunately, the cat died during oxygen therapy. Necropsy examination revealed an increase in cardiac silhouette and ventricular septal defect of 2cm in diameter. Macroscopically the lungs were collapsed, with absent and diffusely reddish blackish crepitus, and the liver with blackish red coalescent multifocal areas, interspersed with lighter areas and lobular pattern with irregular brownish multifocal areas intercepted by brownish areas. Thus, the necropsy results together with the history and physical examination of the animal confirmed the diagnosis of Eisenmenger Syndrome, becoming the report of the first case, in a cat, in Brazil.(AU)

Effects of different lipid sources on intake, digestibility and purine derivatives in hair lambs.

An experiment was conducted to evaluate the effects of different lipid sources on the nutrient intake, digestibility and purine derivative excretion of lambs. Thirty-five 60-day-old, male, non-castrated Santa Ines lambs with an initial average body weight (BW) of 13.00 ± 1.80 kg were used in a randomized complete block design with seven blocks and five treatments. The experimental treatments consisted of a control diet without supplemental lipids and four test diets with different lipid supplements, selected according to the degree of ruminal protection from hydrogenation: supplementation, being supplementation with whole cottonseed (WC), supplementation with cashew nut meal (CNM), supplementation with both cottonseed and cashew nut meal (WC-CNM) and supplementation with calcium salts of long-chain fatty acids (Ca-LCFA). The lambs were slaughtered after reaching 28 kg average BW for each treatment. The ether extract intake (EEI) was higher (p < 0.01) for the lipid supplemented compared to control diet lambs. Supplementation with WC decreased the digestibility of dry matter (DM), organic matter (OM), neutral detergent fibre (NDF) and total carbohydrate (TC) (p < 0.01), whereas supplementation with CNM, WC-CNM and Ca-LCFA reduced non-fibrous carbohydrate (NFC) digestibility (p < 0.01). The ether extract (EE) digestibility coefficient was higher with CNM, followed by Ca-LCFA and WC, when compared to WC-CNM and control diets. Nitrogen balance (NB) was not influenced (p > 0.05) by the different lipid sources. A lower purine derivative (PD) excretion and thus lower microbial protein supply (MPS) was observed for animals supplemented with Ca-LCFA (p < 0.01) compared to the WC-CNM and control diets. In conclusion, WC, CNM and WC-CNM supplementation did not have negative effects on MPS, although negative effects have been observed on nutrient digestibility.

Porcentagem de proteína em suplementos para ovinos mantidos em pasto de capim-aruana na época seca / Protein percentage in supplements for sheep grazing Aruana grass on dry season

Objetivou-se avaliar o consumo de forragem e o desempenho de ovinos mantidos em pastagem de capim-aruana, submetidos a porcentagens crescentes de proteína bruta (PB) no suplemento, na época seca. Vinte borregos da raça Santa Inês foram utilizados em delineamento inteiramente ao acaso, com cinco tratamentos e quatro repetições. Os suplementos foram fornecidos em 1,0% do peso corporal, nas porcentagens de 0, 15, 20, 25 e 30%. O aumento de proteína bruta influenciou o consumo total de matéria seca (kg/dia) e a porcentagem do peso vivo, com valores máximos estimados de 1.296g (3,2% de MS) com 21,48 e 21,89% de PB no suplemento, respectivamente. O consumo de forragem máximo, estimado de 893g/dia, ocorreu com a PB de 21,5%. O aumento de PB nos suplementos resultou em efeito quadrático sobre o ganho médio diário, com valor máximo de 104g/dia com a PB de 23% no suplemento. Recomenda-se o uso de suplementos múltiplos com 21 a 23% de PB fornecidos na proporção de 1% do peso corporal (PC) para ovinos mantidos em pastos de capim-aruana na época seca.(AU)

The aim of this study was to evaluate the forage intake and grazing sheep performance keep on Aruana grass subjected to increasing crude protein (CP) levels in the supplement on dry season. Twenty Santa Ines male lambs were used, with initial body weight of 31.80kg by a completely randomized design with five treatments and four replications. The supplements were provided daily at 1% of body weight, with protein levels of 0, 15, 20, 25 and 30%. The increase of the crude protein levels promoted a squarely effect on dry matter intake (kg/day and % of BW), with maximum estimated values of 1296g and 3.2% of DM in CP levels of 21.48 and 21.89, respectively. The maximum forage intake estimated of 893g/day occurred in CP level de 21.51%. The increased of crude protein level in supplements increased squarely the average daily gain, with a maximum of 104g/day, for the 23% crude protein in the supplement. Thus, the use of the multiple supplements supplied in 1% of body weight with CP levels ranged 21 a 23% is indicated for sheep grazing Aruana grass on dry season.(AU)

Porcentagem de proteína em suplementos para ovinos mantidos em pasto de capim-aruana na época seca / Protein percentage in supplements for sheep grazing Aruana grass on dry season

Objetivou-se avaliar o consumo de forragem e o desempenho de ovinos mantidos em pastagem de capim-aruana, submetidos a porcentagens crescentes de proteína bruta (PB) no suplemento, na época seca. Vinte borregos da raça Santa Inês foram utilizados em delineamento inteiramente ao acaso, com cinco tratamentos e quatro repetições. Os suplementos foram fornecidos em 1,0% do peso corporal, nas porcentagens de 0, 15, 20, 25 e 30%. O aumento de proteína bruta influenciou o consumo total de matéria seca (kg/dia) e a porcentagem do peso vivo, com valores máximos estimados de 1.296g (3,2% de MS) com 21,48 e 21,89% de PB no suplemento, respectivamente. O consumo de forragem máximo, estimado de 893g/dia, ocorreu com a PB de 21,5%. O aumento de PB nos suplementos resultou em efeito quadrático sobre o ganho médio diário, com valor máximo de 104g/dia com a PB de 23% no suplemento. Recomenda-se o uso de suplementos múltiplos com 21 a 23% de PB fornecidos na proporção de 1% do peso corporal (PC) para ovinos mantidos em pastos de capim-aruana na época seca...

The aim of this study was to evaluate the forage intake and grazing sheep performance keep on Aruana grass subjected to increasing crude protein (CP) levels in the supplement on dry season. Twenty Santa Ines male lambs were used, with initial body weight of 31.80kg by a completely randomized design with five treatments and four replications. The supplements were provided daily at 1% of body weight, with protein levels of 0, 15, 20, 25 and 30%. The increase of the crude protein levels promoted a squarely effect on dry matter intake (kg/day and % of BW), with maximum estimated values of 1296g and 3.2% of DM in CP levels of 21.48 and 21.89, respectively. The maximum forage intake estimated of 893g/day occurred in CP level de 21.51%. The increased of crude protein level in supplements increased squarely the average daily gain, with a maximum of 104g/day, for the 23% crude protein in the supplement. Thus, the use of the multiple supplements supplied in 1% of body weight with CP levels ranged 21 a 23% is indicated for sheep grazing Aruana grass on dry season...

Antiplatelet activity and structure-activity relationship study of Pyrazolopyridine Derivatives as potential series for treating thrombotic diseases.

AIM: Platelets plays a central role in hemostatic processes and consequently are similarly involved in pathological processes, such as arterial thrombosis and atherosclerosis. Herein we described the synthesis, antiplatelet profile and structure-activity relationship (SAR) of a new series of N'-substitutedphenylmethylene-1H-pyrazolo[3,4-b]pyridine-carbohydrazide derivatives (3a-3k). METHODS: These compounds were synthesized in good yield and tested in platelet aggregation assays using collagen, ADP and arachidonic acid as agonists. We also performed a SAR studies using SPARTAN' 08 program, in silico ADMET screening and the Lipinski " rule of five " using Osiris Property Explorer and molinspiration on-line programs. RESULTS: Interestingly, the new compounds were active against collagen and arachidonic acid (AA) with the two most actives compounds (3a and 3c - IC(50)=61 microM and 68 microM respectively) almost 5-fold more potent than aspirin (IC(50)=300 microM). These derivatives showed low theoretical toxicity risks in in silico ADMET screening and fulfilled the Lipinski rule of five, suggesting good oral biodisponibility. CONCLUSION: This work showed carbohydrazide group as potential for designing new antiplatelets. On that purpose, 3a and 3c may act as prototypes to generate more efficient and safe molecules for treating thrombotic diseases.

Origin and distribution of the femoral nerve in fetuses of zebu-crossed bovines

In this study the femoral nerve origin and distribution was assessed through the dissection of 30 fetuses of zebu-crossed bovines, 20 males and 10 females. These animals samples fixation in 10% formaldehyde aqueous medium occurred either by subcutaneous, intra-muscle, and intra-cavity injections in different sites, or by immersion of the mentioned pieces in vessels containing the same medium. The femoral nerve originated from the forth (L4), fifth (L5), and sixth (L6) spinal lumbar ventral branches in 14 animals (46.7%), from L4 and L5 in 13 samples (43.3%), and L5 and L6 in three cases (10%). In the course of its way, on both antimeres the mentioned nerve was branched to the greater psoas (100%), iliac (100%), pectinal (56.7%), femoral quadriceps (100%), muscles, and gave off saphena nerve, which gave branches for the pectinal (43.3%) and sartorius (100%) muscles and continued distally along the saphena artery to spread on the medial face of the knee and leg medial articulation skin. Statistically, there was no significant difference between the muscle branch frequencies given by the femoral nerve to the right and left antimeres. The obtained results related to the femoral nerve origin and distribution in fetuses of zebu-crossed bovines generally presented common characteristics with the ruminant corresponding data found in the literature, and this information is important as the basis for clinical or surgical approaches involving the studied structures.