Arylsulfonyl histamine derivatives as powerful and selective α-glucosidase inhibitors.

A series of simple N-arylbenzenesulfonyl histamine derivatives were prepared and screened against α-glucosidase. Inhibition was in the micromolar range for several N α,N τ-di-arylsulfonyl compounds, with N α,N τ-di-4-trifluorobenzenesulfonyl histamine (IId) being the best inhibitor. Compound IId is a reversible and competitive α-glucosidase inhibitor, and presented good selectivity with respect to other target enzymes, including ß-glucosidase and α-amylase, and interesting predicted physicochemical properties. Docking studies have been run to postulate ligand-enzyme interactions to account for the experimental results. In vivo, compound IId produced a similar hypoglycemic effect to acarbose with half of its dose.

Poultry rearing on perforated plastic floors and the effect on air quality, growth performance, and carcass injuries - Experiment 2: Heat stress situation.

Previously, we reported the effect of rearing conditions (plastic floors and air quality) on carcass injury development of broiler chickens at thermal comfort. In this study, the same rearing conditions were tested at thermal stress. The birds were reared in 2 climatic chambers, and the experiment followed a completely randomized design with one factor, flooring material: wood shaving or perforated plastic. The birds were divided into 16 experimental pens, being 8 females and 8 males. The studied parameters were the same as the previous study (ammonia concentration, carbon dioxide, performance, carcass yield, and variability, and scores of hygiene, gait and chest, and hocks and footpad lesions). Higher ammonia (15 ppm vs. 4 ppm) and carbon dioxide (1,000 ppm vs. 850 ppm) concentration was seen at d 42 for the wood shavings floor as compared to the perforated plastic floor, respectively. Regarding gender, males had better performance than females at 42 d of age on both floor types. Males reared on wood shavings showed a higher meat production (29.049 kg/m2) than females (24.700 kg/m2). There were observed breast lesion incidences of 10.4% (score 1) in males reared on the plastic floor, as well higher incidence of hock injury and footpad dermatitis. Chickens reared on plastic flooring showed better hygiene than chickens reared on wood shavings. Our findings revealed that the use of perforated plastic flooring in a heat stress situation can improve the air quality (less CO2 and NH3 concentration) and bird cleanliness. On the other hand, chickens are more susceptible to develop lesions in the breast, hock, and footpad. We conclude that the use of plastic flooring in heat stress conditions needs more attention, since chickens are more susceptible to develop lesions on the carcass, being a source of pain, impairing bird wellbeing and causing losses in meat production.

N α-arylsulfonyl histamines as selective ß-glucosidase inhibitors.

N α-benzenesulfonylhistamine, a new semi-synthetic ß-glucosidase inhibitor, was obtained by bioactivity-guided isolation from a chemically engineered extract of Urtica urens L. prepared by reaction with benzenesulfonyl chloride. In order to identify better ß-glucosidase inhibitors, a new series of N α,N τ-di-arylsulfonyl and N α-arylsulfonyl histamine derivatives was prepared. Biological studies revealed that the ß-glucosidase inhibition was in a micromolar range for several N α-arylsulfonyl histamine compounds of the series, N α-4-fluorobenzenesulfonyl histamine being the most powerful compound. Besides, this reversible and competitive inhibitor presented a good selectivity for ß-glucosidase with respect to other target enzymes including α-glucosidase.

Interference of age and supplementation of direct-fed microbial and essential oil in the activity of digestive enzymes and expression of genes related to transport and digestion of carbohydrates and proteins in the small intestine of broilers.

The objectives of this study were to describe alterations that age and dietary inclusion of direct-fed microbial (DFM) Bacillus subtilis (BS) and a specific essential oil (EO) blend (carvacrol, cinnamaldehyde, cineol, and pepper extract) causes in the activity of digestive enzymes (maltase: MALT; aminopeptidase-N: APN; intestinal alkaline phosphate: IAP) and expression patterns of genes related to transport (oligopeptide transporter gene: SLC15A1; Na+-dependent glucose and galactose transporter gene: SLC5A1; Na+-independent glucose, galactose, and fructose transporter gene: SLC2A2; ATPase, Na+/K+ transporting gene: ATP1A1) and digestion (aminopeptidase-N gene: ANPEP; maltase-glucoamylase gene: MGAM; Sucrase-isomaltase gene: SI) of carbohydrates and proteins in the small intestine of broilers. Also, the objective was to analyze if growth performance of broilers is affected by supplementation (BS and EO blend). Day-old male broiler chicks (n = 1,320) were assigned to 5 treatments. Diets included a basal diet (BD) as a negative control (CON); experimental diets were BD + BS; BD + BS + EO; BD + EO; BD + antibiotic growth promoter (AGP) avilamycin was the positive control. Performance was evaluated between 1 to 42 d. Transcript abundance of transport-related genes and digestion-related genes were assayed by RT-qPCR and determined at d 7, 21, and 42. MALT-, APN-, and IAP-specific activities were determined at d 7, 21, and 42. Broilers fed BS had greater SLC15A1 mRNA abundance compared to CON, while EO and AGP were related to higher activities of IAP and APN. Analysis over time revealed higher abundance of MGAM, SLC2A2, SLC15A1, SLC5A1 and SI mRNA at d 42 when compared to d 7. Activity of IAP decreased after d 7 and activity of MALT increased with age. The current study suggests that age had effect over carbohydrate and protein transport and carbohydrate digestion. The supplementation of BS DFM hade evident effect over protein transport and that the use of EO in the diet enhanced the activities of carbohydrate and protein digestion, reflecting improvement in digestive and transport physiology of birds. Changes performed by BS DFM and EO did not favor performance.

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

The effect of replacing corn with low-tannin sorghum on broiler performance, carcass yield, integrity of mucosa of small intestine segments, and activity of membrane enzymes of the jejunum is investigated. A total of 594 male Cobb-500 broiler chicks were randomly assigned to 3 dietary treatments: 100% corn (control), 50% corn replacement with low-tannin sorghum (low sorghum), and 100% corn replacement with low-tannin sorghum (high sorghum). Body weight gain, feed consumption, feed conversion, and carcass yield were determined at 7, 21, and 42 d, and segments of the small intestine were collected. Feed conversion and weight gain were impaired at d 42 in broilers fed the high-sorghum diet, but no differences were observed for carcass yield among the treatments (P > 0.05). Crypt cell mitotic index of the jejunum and ileum at d 21 and 42 was lower in broilers fed the control diet than in those fed low- and high-sorghum diets (P < 0.05). Aminopeptidase activity was higher in broilers fed the control diet than in those fed low- and high-sorghum diets irrespective of age (P < 0.05). Conversely, intestinal alkaline phosphatase activity in the small intestine did not differ among the dietary treatments (P > 0.05). Our results indicate that 50% corn replacement with low-tannin sorghum is suitable for broiler diets, whereas 100% corn replacement with low-tannin sorghum had negative effects on the intestinal mucosa and performance of broilers at 42 d.

Fuzzy modeling to predict chicken egg hatchability in commercial hatchery.

Experimental studies have shown that hatching rate depends, among other factors, on the main physical characteristics of the eggs. The physical parameters used in our work were egg weight, eggshell thickness, egg sphericity, and yolk per albumen ratio. The relationships of these parameters in the incubation process were modeled by Fuzzy logic. The rules of the Fuzzy modeling were based on the analysis of the physical characteristics of the hatching eggs and the respective hatching rate using a commercial hatchery by applying a trapezoidal membership function into the modeling process. The implementations were performed in software. Aiming to compare the Fuzzy with a statistical modeling, the same data obtained in the commercial hatchery were analyzed using multiple linear regression. The estimated parameters of multiple linear regressions were based on a backward selection procedure. The results showed that the determination coefficient and the mean square error were higher using the Fuzzy method when compared with the statistical modeling. Furthermore, the predicted hatchability rates by Fuzzy Logic agreed with hatching rates obtained in the commercial hatchery.

Detection of antifungal compounds in Polygonum ferrugineum Wedd. extracts by bioassay-guided fractionation. Some evidences of their mode of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum ferrugineum Wedd. (Polygonaceae) is used to heal infected wounds and as antiseptic, antibiotic or antifungal in the traditional Argentinean medicine. The present investigation was carried out to evaluate the antifungal properties of different extracts of aerial parts of Polygonum ferrugineum, in order to give support to its ethnopharmacological use and to isolate the compounds responsible for the antifungal properties. The most active compounds were tested for their capacity of producing hyphae malformations, similar to those previously observed for crude extracts. MATERIALS AND METHODS: Agar Dilution Method (ADM) and Agar Overlay Bioautography (AOB) were used for bioassay-guided fractionation of the aerial part extracts against a panel of human opportunistic pathogenic fungi. The Neurospora crassa assay, followed by Optical Microscopy and Scanning Electron Microscopy observation, was used for studies of mechanisms of action. RESULTS: MeOH extract and DCM and Hex sub-extracts, but not Aq, EtOAc or BuOH ones possess antifungal activity. Of the seven isolated compounds, cardamonin 2 showed a selective inhibition of Epidermophyton floccosum with a very low MIC (=6.2 µg/mL) and pashanone 1 possessed moderate antifungal activity (MICs=25-50 µg/mL) but a broader spectrum of action. Chalcone 2, but not 1, induced swelling and shortening of the Neurospora crassa hyphae, similar as those caused by the crude DCM extract. CONCLUSIONS: The bioassay-guided fractionation of Polygonum ferrugineum DCM extract allowed the isolation of five active compounds. Among them, cardamonin 2 showed the highest antifungal activity and selectivity towards Epidermophyton floccosum; in addition, it induced Neurospora crassa malformations that are similar than those produced by the crude DCM extract. These results give additional support to the ethnopharmacological use of Polygonum ferrugineum as antifungal agent.

Role of brain nitric oxide in the thermoregulation of broiler chicks.

Nitric oxide (NO) plays a key role in body temperature (Tb) regulation of mammals, acting on the brain to stimulate heat loss. Regarding birds, the putative participation of NO in the maintenance of Tb in thermoneutrality or during heat stress and the site of its action (periphery or brain) is unknown. Thus, we tested if NO participates in the maintenance of chicks' Tb in those conditions. We investigated the effect of intramuscular (im; 25, 50, 100mg/kg) or intracerebroventricular (icv; 22.5, 45, 90, 180 microg/animal) injections of the non selective NO synthase inhibitor L-NAME on Tb of 5-day-old chicks at thermoneutral zone (TNZ; 31-32 degrees C) and under heat stress (37 degrees C for 5-6h). We also verified plasma and diencephalic nitrite/nitrate levels in non-injected chicks under both conditions. At TNZ, 100mg/kg (im) or 45, 90, 180 microg (icv) of L-NAME decreased Tb. A significant correlation between Tb and diencephalic, but not plasma, nitrite/nitrate levels was observed. Heat stress-induced hyperthermia was inhibited by all tested doses of L-NAME (im and icv). Tb was correlated neither with plasma nor with diencephalic nitrite/nitrate levels during heat stress. These results indicate the involvement of brain NO in the maintenance of Tb of chicks, an opposite action of that observed in mammals, and may modulate hyperthermia.

Breeder age and bone development in broiler chicken embryos / Idade da matriz e desenvolvimento ósseo em embriões de frango de corte

The effect of breeder age on long bone development was studied in chicken embryos from 12 days of incubation until hatching. Fertile eggs were incubated and randomly assigned in a 2 x 6 factorial arrangement (two breeder ages - 38 and 60 weeks and six incubation days - 12, 14, 16, 18, 20, and 21). Enzymatic activity of acid and alkaline phosphatases in tibial epiphyses and weights as well as length and width in tibias and femurs of the embryos were determined. Tartrate-resistant acid and alkaline phosphatases activity in epiphyses was not affected by breeder age. Absolute weight and width of femur and tibia were larger in 60-week-old embryos compared to 38-week-old. Enzymatic activity and morphometric measurements increased with incubation day, independently of breeder age. The results showed that the process of endochondral ossification during the last two thirds of embryo development was not influenced by the age of the breeders. Although, in terms of absolute weight, the long bones of embryos from older breeders were heavier, which was associated with the larger width of the bones, but and not with their length.

O efeito da idade da matriz sobre o desenvolvimento dos ossos longos foi estudado em embriões de frango de 12 dias de incubação até o nascimento. Ovos férteis foram incubados e distribuídos em delineamento inteiramente casualizado em arranjo fatorial 2 x 6 (duas idades de matriz - 38 e 60 semanas e seis dias de incubação - 12, 14, 16, 18, 20 e 21 dias). Determinou-se a atividade enzimática das fosfatase alcalina e ácida-resistente ao tartrato no peso e nas epífises da tíbia, no comprimento e na largura da tíbia e do fêmur. A atividade das fosfatases não foi afetada pela idade da matriz. O peso absoluto e a largura de fêmur e tíbia foram maiores nos embriões das matrizes com 60 semanas de idade. Atividade enzimática e medidas morfométricas aumentaram com o dia de incubação independentemente da idade da matriz. Concluiu-se que o processo de ossificação endocondral durante os dois últimos terços de desenvolvimento embrionário não foi influenciado pela idade das matrizes. No entanto, em termos de peso absoluto, os ossos longos de embriões provenientes de matrizes velhas foram mais pesados o que foi associado à maior largura e não ao maior comprimento dos ossos.

Efeito da temperatura ambiente e da restrição alimentar protéica ou energética sobre o ganho de peso e crescimento ósseo de frangos de corte / Effect of environmental temperature and protein or energy restriction on body weight gain and broiler chicken bone growth

Avaliou-se o efeito da restrição alimentar qualitativa, protéica ou energética sobre o ganho de peso e desenvolvimento ósseo de frangos criados em diferentes temperaturas ambientes. O delineamento experimental foi inteiramente ao acaso, com os tratamentos em um esquema fatorial 3 3, com os fatores: restrição alimentar (R0 = ad libitum; R1 = restrição energética; R2 = restrição protéica) e temperatura ambiente (T1 = 18ºC; T2 = 25ºC; T3 = 33º C). Do 8º ao 14º dia, os frangos foram submetidos à restrição energética (2565kcal de EM/kg e 20 por cento de proteína bruta) ou protéica (2850kcal de EM/kg e 15 por cento de proteína bruta), sendo, posteriormente, alimentados à vontade. A restrição protéica resultou em menor ganho de peso e menor diâmetro do fêmur no 14º dia de idade. Não foram observadas diferenças nessas características a partir do 21º dia de idade. O ganho de peso e o crescimento do fêmur não foram influenciados pela restrição energética. A alta temperatura ambiente (33ºC) influenciou negativamente o ganho de peso e o diâmetro do fêmur, a partir do 21º dia, e o comprimento do fêmur, no 42º dia de idade. Tanto a restrição protéica, na segunda semana, quanto a alta temperatura ambiente, a partir do 21º dia de idade, reduziram o ganho de peso e o crescimento do fêmur de frangos.

Somatotrophic and thyroid hormones around the onset of lay in broiler breeders under different conditions.

Somatotrophic and thyroid hormones were determined around the onset of reproduction in broiler breeders reared in two different housing systems [dark, close-sided house (CH) and conventional, open-sided house (OH)]. In both groups age-related changes were obvious for thyroxine (T4), growth hormone (GH) and insulin-like growth factor (IGF-1); levels of T4 decreased, especially between 24 and 28 weeks in both groups; concomitantly GH sharply increased over the same period. A transient peak in triiodothyronine (T3) occurred between 25 and 27 weeks. The effect of housing was only present after the onset of lay. Between weeks 27-28 and the end of the period studied, the CH group showed higher levels of GH and T3 but lower T4 levels as compared to the OH group. A significant increase in GH after onset of lay, without any significant rise in T3 or in IGF-I, could point to a relative insensitivity to high plasma GH levels. Changes at GH receptor level, together with an increased pituitary GH secretion and/or decreased GH turnover may be expected. This may indicate that hypothalamo-pituitary changes at the onset of lay not only imply changes of gonadotrophic cell function, but also other hormonal axes. The relatively decrease in T4 without changes in T3, may point to a decrease in the activity of the thyrotropic axis.

Efeito da restriçäo alimentar inicial e da temperatura ambiente sobre o desenvolvimento de vísceras e ganho compensatório em frangos de corte / Effect of early quantitative feed restriction and environmental temperature on viscera growth and compensatory gain of broiler chickens

O presente trabalho teve como objetivo estudar o efeito da restriçäo alimentar quantitativa inicial e da temperatura ambiente sobre o desenvolvimento de vísceras e ganho compensatório em frangos de corte. Foram utilizados 540 frangos machos, em um delineamento inteiramente ao acaso, segundo esquema fatorial 2 x 3, com os fatores programa alimentar (ad libitum e restrito do 7§ ao 14§ dia de idade) e temperatura ambiente (quente, termoneutra e fria). A restriçäo alimentar näo afetou o peso relativo do fígado e do coraçäo, mas reduziu significamente o peso e o comprimento dos intestinos ao final do período de restriçäo (14 dias de idade). Näo foi observado efeito significativo da restriçäo alimentar sobre o desenvolvimento das vísceras estudadas aos 42 dias de idade. Peso vivo, ganho de peso e consumo de raçäo dos frangos com restriçäo alimentar foram significamente menores aos 28 dias de idade, porém näo foram observadas diferenças entre essas variáveis aos 42 dias de idade, demonstrando ganho compensatório durante o período de realimentaçäo. O peso relativo das vísceras näo foi afetado pela temperatura de criaçäo aos 42 dias de idade, exceto o coraçäo. Consumo de raçäo, ganho de peso e peso vivo aos 42 dias de idade foram significativamente menores nas aves mantidas em altas temperaturas

Influence of early quantitative food restriction on long bone growth at different environmental temperatures in broiler chickens.

1. This investigation was carried out to study the influence of early quantitative food restriction (40% of ad libitum intake from 7 to 14 d of age) and environmental rearing temperature (thermoneutral, cold and hot) on long bone (tibia, femur and humerus) development in broiler chickens. 2. Tibia, femur and humerus were obtained at the ages of 14, 21, 28, 35 and 42 d, and the variables studied were: length and width (mm, expressed as absolute values), bone breaking strength (kgf) and bone weight/bone length index (BW/BL, mg/mm). 3. All bone variables increased with bird age. Food restriction reduced bone length and width but did not affect bone weight. High environmental rearing temperature reduced bone length and width at 42 d of age. Bone strength was not affected by environmental temperature but the calculated BW/BL index was reduced by heat exposure. 4. The findings suggest that food restriction and high environmental rearing temperature reduce long bone growth; bone breaking strength was affected by bird age but not by food restriction nor rearing ambient temperature.

In vitro evaluation of antifungal properties of phenylpropanoids and related compounds acting against dermatophytes.

Thirty-four arylpropanoids and related compounds were evaluated in vitro for antifungal properties. Among them, 22 phenyl-, 4 naphthyl-, and 4 phenanthrylpropanoids; naphthalene; phenanthrene; and 2-chloro-1-hexyl-1-propanone were tested against dermatophytes by the agar dilution method. alpha-Halopropiophenones exhibited a broad spectrum of activities against Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum, and Epidermophyton floccosum, with MIC values between 0.5 and >50 microg/mL. Keto, alcohol, and alpha-haloketo propyl derivatives of naphthalene and phenanthrene also showed very good activity against all dermatophytes tested, clearly showing that in these series, a halogen atom is not necessary for activity. Phenanthryl derivatives were more active (MICs, 3-20 microg/mL) than naphthyl ones (MICs, 3-50 microg/mL). A structure-activity relationship study was carried out and aided in establishing the structural requirements of arylpropanoids for antifungal activities. Because dermatophytes are a group of fungi that characteristically infect the keratinized areas of the body, these new series of antifungal compounds open the possibility of discovering new topical antifungal drugs for the treatment of dermatomycoses, which are frequently very difficult to eradicate.

Effect of indomethacin on hyperthermia induced by heat stress in broiler chickens.

An investigation was carried out to verify whether the heat stress hyperthermia response of broilers is prostaglandin-dependent. Male broiler chickens of the Hubbard-Petterson strain, aged 35-49 days, were used. Chickens were injected with indomethacin (1 mg/kg intraperitoneally) 15 min before or 2 h after heat exposure (at 35 degrees C for 4 h), and rectal temperature was measured before injection and up to 4 h thereafter. Birds were separated into two groups with and without access to water during heat stress. The increase in rectal temperature was lower (P < 0.05) in birds with access to drinking water during heat exposure. All birds injected with indomethacin exhibited an increase in rectal temperature, irrespective of whether indomethacin was administered before or in the course of the rise in temperature. The results revealed that the increase in rectal temperature during heat exposure is not prostaglandin-dependent, and that the use of cyclooxigenase inhibitors is not recommended to attenuate heat stress hyperthermia in broiler chickens.

Effects of endotoxin, interleukin-1 beta and prostaglandin injections on fever response in broilers.

1. The effect of endotoxin, interleukin-1 beta and prostaglandin on fever response was studied in 80 broilers (Hubbard strain). Endotoxin (E. coli, LPS) was injected i.v. (1.5 micrograms/kg) and icv (1.5 micrograms/bird); interleukin-1 (human recombinant IL-1 beta, 80 pg/bird) and prostaglandin E2 (5 micrograms/bird) were injected icv. Indomethacin (10 mg/kg, i.v.) pretreatment was also used before i.v. endotoxin injection. 2. The results showed that indomethacin was able to block the fever response induced by i.v. endotoxin injection, and IL-1 beta and PGE2 were both effective in producing fever when injected icv. These data suggest a prostaglandin-mediated fever response by broilers, and also a strong evidence of the involvement of endogenous pyrogen (interleukin-1) in fever response in birds.

Effect of age and strain on haematological and gasometric parameters in selected and non-selected broiler chickens

Objetivou-se investigar o efeito de idade e linhagem sobre parâmetros hematológicos e gasométricos de frangos selecionados e näo selecionados. Foram utilizados somente frangos machos, sendo 40 selecionados e 10 näo-selecionados. Amostras de sangue foram colhidas aos 21 e 42 dias de idade e determinados os parâmetros hematológicos (eritrócito, leucócito, hemoglobina, hematócrito, volume globular médio, hemoglobina globular média e concentraçäo de hemoglobina no eritrócito), e os parâmetros gasométricos (pH, pressäo parcial de oxigênio e pressäo parcial de dióxido de carbono). Os resultados mostraram que os parâmetros hematológicos e gasométricos säo afetados pela idade e linhagem do frango. As aves selecionadas apresentaram um número de eritrócito menor e um volume globular médio maior aos 21 dias de idade quando comparados aos animais de 42 dias de idade, e uma relaçäo inversa foi verificada nos frangos näo selecionados. Estes dados sugerem que quando jovens os frangos selecionados podem ser mais sensíveis às alteraçöes nos parâmetros pulmonares e desenvolver a síndrome da Ascite