Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.

Indicadores bioquímicos séricos e do líquido peritoneal de equinos submetidos à obstrução intestinal

Twenty-four horses were distributed into four different groups, instrumented control (GI), duodenum obstruction (GII), ileum obstruction (GIII) and large colon obstruction (GIV). Serum and peritoneal fluid analysis of aspartate aminotransferase, creatine kinase, lactate dehydrogenase, alkaline phosphatase, inorganic phosphorus and lactate were measured. Samples were collected one hour before the surgical procedure (T0); 3 hours after the obstruction (T3ob), 1, 3, 12, 24, 120 and 168 hours after the beginning of reperfusion/deobstruction. Duodenal (GII) and ileum (GIII) obstructions changed serum and peritoneal fluid biochemical analysis. However, only lactate, lactate dehydrogenase, creatine kinase and inorganic phosphorus concentrations were abnormal in peritoneal fluid three hours after the obstruction. The biochemical analysis of peritoneal fluid allowed a faster diagnostic of intestinal alterations than the serum analysis; hence it should be prioritized when pre-operatory colic assessment is carried out.

Pulpal and periodontal diseases increase triglyceride levels in diabetic rats

Objectives: The aim of this study was to evaluate triglyceride and cholesterol levels in diabetic rats and their relationship with pulpal and periodontal diseases. Methods: Eighty male rats (Rattus norvegicus albinus, Wistar) were divided into the following eight groups comprising ten animals each: normal rats (G1), rats with pulpal diseases (G2), rats with periodontal diseases (G3), rats with both pulpal and periodontal diseases (G4), diabetic rats (G5), diabetic rats with pulpal diseases (G6), diabetic rats with periodontal diseases (G7), and diabetic rats with both periodontal and pulpal diseases (G8). Diabetes was induced by injecting streptozotocin, periapical lesions were induced by exposing pulpal tissue to the oral environment, and periodontal diseases were induced by periodontal ligature. The animals were killed after 30 days, and lipid profile was enzymatically measured using Trinder's method. The total assessed values were statistically analyzed by analysis of variance and Tukey test (p < 0.05). Results: The triglyceride levels of diabetic rats with periodontal disease and of diabetic rats with both periodontal and pulpal diseases were significantly higher than those of normal rats and nondiabetic group rats, respectively. The differences in the cholesterol levels among the groups were not significant. Conclusions: We found that the association of pulpal and periodontal diseases with diabetes increased triglyceride levels in rats. Clinical significance: Changes in lipid profile may be related to the presence of oral infections and diabetes. © 2012 Springer-Verlag Berlin Heidelberg.

Effects of vaccination against reproductive diseases on reproductive performance of beef cows submitted to fixed-timed AI in Brazilian cow-calf operations

The objectives were to assess incidence of pregnancy losses, associate this outcome with immunization programs against reproductive diseases, and evaluate the effects of vaccination against bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), and Leptospira spp., on reproductive efficiency of Brazilian cow-calf operations. In experiment 1, 7614 lactating Nelore cows from 18 ranches were assigned to the same estrus synchronization and fixed-time AI protocol (ESFTAI; Days -11 to 0). Pregnancy status was determined with transrectal ultrasonography on Days 30 and 120 after AI. Pregnancy loss was deemed to have occurred when cows were pregnant on Day 30 but nonpregnant on Day 120. Incidence of pregnancy loss across all ranches was 4.1%; pregnancy losses were detected (P < 0.10) in 14 ranches but not detected (P > 0.11) in four ranches. Pregnancy loss was lower (P ≤ 0.02) in ranches that vaccinated against BoHV-1, BVDV, and Leptospira spp. compared with ranches that did not vaccinate, or only vaccinated against Leptospira spp. In experiments 2 and 3, lactating Nelore cows (N = 1950 and 2793, respectively) from ranches that did not have a history of vaccinating against reproductive diseases (experiment 2), or only vaccinated against Leptospira spp. (experiment 3), were assigned to the same ESFTAI used in experiment 1. Within each ranch, cows received (VAC) or not (CON) vaccination against BoHV-1, BVDV, and Leptospira spp. at the beginning of the ESFTAI (Day -11) and 30 days after (Day 41) AI. In experiment 2, VAC cows had greater (P ≤ 0.05) pregnancy rates compared with CON on Days 30 and 120. In experiments 2 and 3, pregnancy loss was reduced (P ≤ 0.03) in primiparous VAC cows compared with CON cohorts. In experiment 4, 367 primiparous, lactating Nelore cows previously vaccinated against Leptospira spp. were assigned to the same ESFTAI used in experiment 1. Cows received VAC, or the same vaccine 30 days before (Day -41) and at the beginning (Day -11) of the ESFTAI (PREVAC). Pregnancy rates on Days 30 and 120 were greater (P ≤ 0.05) in PREVAC cows compared with VAC cows. In conclusion, pregnancy losses affected reproductive and overall efficiency of Brazilian cow-calf operations, and might be directly associated with BoHV-1, BVDV, and Leptospira spp. infections. Hence, vaccinating cows against these pathogens, particularly when both doses are administered before fixed-time AI, improved reproductive performance in Brazilian cow-calf systems. © 2013 Elsevier Inc.

Telomere length and its relationship with chronic diseases - New perspectives for periodontal research

Objective: The ageing process is accompanied by a variety of cellular modifications, and telomere shortening is a common finding. Large epidemiological studies have reported an association between shorter telomere length in peripheral leukocytes and several inflammatory diseases of the elderly including diabetes, atherosclerosis and, recently, periodontitis. The primary aim of this study was to critically discuss available evidence regarding the potential mechanisms relating shorter telomeres to periodontitis. Design: A narrative literature review was performed to report evidence relating shorter telomeres to the ageing process and inflammation. Then, we searched MEDLINE (1950 to May 2012) and ISI WEB OF SCIENCE (1950 to May 2012) databases for the combination of the terms 'telomere' and 'periodontitis'. Results: Although these associations suggest a possible role of telomere attrition in the onset or evolution of chronic inflammatory diseases, only two studies addressed the relationship between telomere length and periodontitis. Conclusion: We suggest that the chronic inflammatory burden observed in people with chronic periodontitis could represent the driver of telomere shortening. However, further evidence is needed to confirm whether inflammation is the cause or the consequence of the shorter leukocyte telomere length observed in people with periodontitis. © 2012 Elsevier Ltd. All rights reserved.

Effects of vaccination against reproductive diseases on reproductive performance of lactating dairy cows submitted to AI

Four experiments evaluated the effects of vaccination against bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), and Leptospira spp. on reproductive performance of lactating dairy cows without (experiments 1, 2, and 3) or with previous vaccination against these diseases (experiment 4). Cows were assigned to a fixed-time AI protocol (FTAI; d -11 to 0) in all experiments, as well as AI 12. h upon estrus detection in experiment 3. Pregnancy status was determined with transrectal ultrasonography on d 30 and 71 (d 60 for experiment 3) after AI. Pregnancy loss was considered in cows pregnant on d 30 but non-pregnant on the subsequent evaluation. In experiment 1, 853 cows received (VAC) or not (CON) vaccination against BoHV-1, BVDV, and Leptospira spp. at the beginning of the FTAI (d -11) and 30. d after AI. Pregnancy loss was reduced (P=0.03) in VAC cows compared with CON. In experiment 2, 287 cows received VAC or CON 30. d prior to (d -41) and at the beginning (d -11) of the FTAI. Pregnancy rates on d 30 and 71 were greater (P≤0.03) in VAC cows compared with CON. In experiment 3, 1680 cows with more than 28. d in milk were randomly assigned to receive VAC or CON with doses administered 14. d apart, and inseminated within 15-135. d after the second dose. Pregnancy rates on d 30 and 60 were greater (P≤0.02) in VAC cows compared with CON. In experiment 4, 820 cows received (REVAC) or not (CON) revaccination against BoHV-1, BVDV, and Leptospira spp. at the beginning of the FTAI protocol (d -11). Pregnancy rates and loss were similar (P≥0.54) between treatments. Hence, vaccinating naïve cows against BoHV-1, BVDV, and Leptospira spp. improved reproductive efficiency in dairy production systems, particularly when both doses were administered prior to AI. © 2013 Elsevier B.V.

Hepatoencephalopathy syndrome due to Cassia occidentalis (Leguminosae, Caesalpinioideae) seed ingestion in horses

Cassia occidentalis is a bush from the Leguminosae family, subfamily Caesalpinoideae, and is a toxic plant of veterinary interest due to the occasional contamination of animal rations. This report describes the clinical and histopathological findings of an outbreak of C.occidentalis poisoning in horses. Twenty mares were poisoned after consuming ground corn contaminated with 8% of C.occidentalis seeds. Of the 20 animals affected, 12 died: 8 mares were found dead, 2 died 6h after the onset of clinical signs compatible with hepatic encephalopathy and the 2 other animals were subjected to euthanasia 12h after the onset of the clinical signs. The remaining 8 mares presented with mild depression and decreased appetite, but improved with treatment and no clinical sequelae were observed. In 6 animals that underwent a necropsy, an enhanced hepatic lobular pattern was noted and within the large intestine, a large number of seeds were consistently observed. Hepatocellular pericentrolobular necrosis and cerebral oedema were the main histological findings. In one mare, there was mild multifocal semimembranosus rhabdomyocytic necrosis and haemorrhage. Seeds collected from intestinal contents and sifted from the culpable feedstuff were planted. Examination of the leaves, flowers, fruits and seeds of the resultant plants identified C.occidentalis. Horses poisoned by C.occidentalis seeds demonstrate clinical signs associated with hepatoencephalopathy and frequently die suddenly. Lesions primarily involve the liver and secondarily, the central nervous system. Cassia occidentalis poisoning should be considered a differential diagnosis in horses with hepatoencephalopathy and special caution should be taken with horse rations to avoid contamination with seeds of this toxic plant. © 2012 EVJ Ltd.

Annexin-A1 peptide down-regulates the leukocyte recruitment and up-regulates interleukin-10 release into lung after intestinal ischemia-reperfusion in mice

Background: Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion. Results: The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10. Conclusion: Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion. © 2013 Guido et al.; licensee BioMed Central Ltd.

Simultaneity of the anthropometric markers of adiposity and chronic diseases in women

Aim. The aim of this paper was to investigate the relationship between the accumulation of different anthropometric indicators and the prevalence of some chronic diseases in women over 40 years of age. Methods. The sample was comprised of 562 women between 40 and 95 years of age (64.5 ± 11.4) attended by the research projects were carried out in two cities in southeastern Brazil. Anthropometric measurements were taken: weight, height, waist circumference, hip circumference, and the values of BMI and WHR were later calculated. The referenced morbidity questionnaire was also applied, based on the Standard Health Questionnaire (SHQ), which analyzes the presence of degenerative chronic diseases in the adult population. For the statistical treatment, the chi-square and binary logistic regression tests were performed, with significance set at 5%. Results. The relationship between three changes in the anthropometric indicators and the greater incidence of diseases continued significant for hypertension (OR=3.77 [95% CI: 2.14-6.65], =P=0.001), and for endocrine and metabolic diseases (OR=2.59 [95%: 1:47 to 4:32], =P=0.001), regardless of the effects of age and physical activities. Conclusion. The simultaneity of body fat indicators is more strongly associated with the prevalence of some chronic diseases (hypertension, endocrine, and metabolic), relative to the individualized use of anthropometric indicators.

Nanotechnology-based drug delivery systems for treatment of hyperproliferative skin diseases - a review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Supplementation with protected fat to manage gastro-intestinal nematode infections in Santa Ines sheep

This experiment aimed to determine the influence of supplementation with protected fat on nematode infections in periparturient sheep or sheep in their final stage of pregnancy. Fifty Santa Ines ewes received 200 g of concentrate/animal/day, mineral salt and water and were grouped according to their weight, hematocrit and the number of eggs per gram of feces (EPG). Two diets were used: a control treatment and a treatment consisting of supplementation with 30 g/animal/day of protected fat in the concentrate. Three monthly evaluations were performed over a total of 84 days of testing. The variables analyzed were weight, body condition, EPG and coprocultures; blood tests were performed for the determination of packed cell volume, hemoglobin concentration and total plasma protein, and leukograms and eosinophil counts were performed. For weight and hemoglobin concentrations, interactions were observed between diet and collection date (P<0.05); body condition, total plasma protein, packed cell volume and total leukocytes did not differ statistically among treatments (P> 0. 05) but did differ by collection day (P <0.05). The EPG and eosinophil counts did not differ statistically by either diet or collection date (P>0.05). The genus Haemonchus was predominant, followed by the genera Cooperia, Trichostrongylus and Oesophagostomum. The protected fat did not decrease EPG and did not improve the blood parameters of infected sheep.

Effects of corn replacement by sorghum in broiler diets on performance and intestinal mucosa integrity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of plasma and/or yeast extract on performance and intestinal morphology of piglets from 7 to 63 days of age

The objective of this study was to evaluate the effect of diets supplemented with plasma and/or yeast extract on performance (daily weight gain [DWG], daily feed intake [DFI] and feed conversion [FC]) and intestinal morphology of piglets from 7 to 63 days of age. A total of 288 piglets aged 7 days and weighing 2.57±0.05 kg were studied. A randomized block design consisting of four experimental diets, six repetitions and 12 piglets per experimental unit was adopted. The pre-starter I (7 to 21 days), pre-starter II (22 to 35 days) and starter I (36 to 49 days) diets were supplemented as follows: control diet (CD): no plasma or yeast extract; plasma (PL) diet: addition of 6%, 4% and 2% plasma; yeast extract (YE) diet: addition of 6%, 4% and 2% yeast extract; plasma + yeast extract (PL+YE) diet: addition of 3%, 2% and 1% plasma and yeast extract each. From 50 to 63 days of age all piglets received the same diet. No difference in performance was observed from 7 to 21 days and from 7 to 28 days of age, whereas DWG was higher from 7 to 35 days in piglets receiving the PL+YE diet (268, 278, 271 and 288 g/day for CD, PL, YE and PL+YE, respectively). From 7 to 49 days and from 7 to 63 days, DWG (330 and 519 g/day, respectively) and DFI (307 and 647 g/day) were higher in animals receiving the PL-YE diet when compared with those consuming CD (DWG: 295 and 486 g/day; DFI: 266 and 594 g/day). No significant differences in intestinal morphology were observed between piglets receiving the different diets. The combination of plasma and yeast extract elevates DWG, but does not affect the intestinal morphology of piglets from 7 to 63 days of age. © 2013 Sociedade Brasileira de Zootecnia.

Effect of dietary betaine supplementation on the performance, carcass yield, and intestinal morphometrics of broilers submitted to heat stress

The objective of this study was to evaluate the effect of betaine in methionine- and choline-reduced diets fed to broilers submitted to heat stress. In total, 1,408 male broilers were randomly distributed into eight treatments, according to 2 × 4 (environment x diet) factorial arrangement, with eight replicates of 2 birds each. Birds were reared environmental chambers under controlled temperature (25-26 °C) or cyclic heat-stressing temperature (25-31 °C). The following diets were tested: positive control (PC), formulated to meet broiler nutritional requirements; negative control (NC), with reduced DL-methionine and choline chloride levels; and with two supplementation levels of natural betaine to the negative control diet (NC+NB1 and NC+NB2). Live performance, carcass traits, and intestinal morphometrics were evaluated when broilers were 45 days of age. The results showed that all evaluated parameters were influenced by the interaction between environment and diet, except for breast meat drip loss. The breakdown of the interactions showed that birds fed the PC diet and reared in the controlled environment had greater breast drip loss than those submitted to the cyclic heat-stress environment. Birds submitted to cyclic heat stress and fed the PC diet presented the lowest feed intake. Feed conversion ratio was influenced only by diet. The FCR of broilers fed the NC+NB2 diet was intermediate relative to those fed the PC and NC diets. The addition of betaine in the diet, with 11.18% digestible methionine and 24.73% total choline reductions, did not affect broiler live performance, carcass yield, or intestinal morphometrics.

Effects of pre-slaughter fasting on broiler welfare, meat quality, and intestinal integrity

The Brazilian Ministry of Agriculture (MAPA) regulations establish 12 hours as the maximum pre-slaughter fasting period for broilers; however, many processing plants have considered this time is not sufficient, and consequently return the birds to the farms, with consequent economic losses and welfare problems. Therefore, it is necessary to investigate the possible effects of longer pre-slaughter fasting times. The objective of the present study was to evaluate the effect of pre-slaughter fasting times longer than those established by MAPA on broiler welfare, breast meat quality, and intestinal integrity. Forty 42-d-old broilers were submitted to different pre-slaughter fasting times: group I: 6 hours, group II 9h, group III 12h, and group IV 15h. Bird welfare was assessed before slaughter. After sacrifice, intestinal samples were collected to assess their morphology and morphometrics, and the Pectoralis major muscle was analyzed for pH and color. There was no influence (p>0.05) of treatments on breast muscle pH or color.There were no significant changes in intestinal morphometrics (p<0.05). Bird behavior was affected (p<0.05), suggesting that welfare was impaired as fasting time increased, but no differences in the analyzed parameters were detected between broilers fasted for 12 or 15 hours. It was concluded that the behavioral differences between birds fasted for 12 and 15 hours are not sufficient to assert that those fasted for 15 hours were in worse welfare conditions.