Protective activity of monoacetone glucose 3-butyrate, prodrug of n-butyric acid, against the fatal effect of encephalomyocarditis virus in mice]

A comparative study was made, in the mouse, on antiviral properties of a prodrug of n-butyric acid derived from monosaccharides: monoacetone glucose 3-butyrate (MAG = 3but), and of a free form of n-butyric acid: arginine butyrate (BuO Arg). Preventive injection of MAG = 3but protected the mice twice as effectively as BuO Arg against the lethal effect of 100 LD50 of encephalomyocarditis virus. Under the same experimental conditions, monoacetone glucose (MAG) used as carrier of the biologically active moiety, was inactive on its own. Antiviral activity of MAG = 3but was shown not to be virucidal, but rather could involve stimulation of the immune system. This capability supplements known anticellular and antitumoral properties. In total these results indicate a prime therapeutic importance for this new molecule, pharmacokinetically suitable, with its very low toxicity, for clinical application. Combined use of MAG = 3but with biological response modifiers which have similar affinity, such as Interferon, is discussed.     

Selective and reversible blockage of a fatty acid odour response in the olfactory bulb of the frog (Rana temporaria).

The lectin concanavalin A (ConA) when applied to the olfactory mucosa (OM) of frog and rat, is reported to partially inhibit electro-olfactogram (EOG) responses to fatty acid odours. Control odours like isoamyl acetate were not affected. We have now studied in the frog whether this treatment affects the corresponding olfactory bulb (OB) response. The OB surface was impregnated with a voltage-sensitive dye (RH 414). Spatial and temporal patterns of odour response were measured by changes in dye fluorescence that occur when OB neurons fire. The apparatus, consisted of an epi-fluorescent microscope coupled to a 64 x 64 pixel CCD photodetection camera. This allowed imaging over an 0.9 mm2 area of the OB glomerular layer to high resolution. When the frog OM was bathed with 5 mg ml(-1) ConA in Ringer's solution, the n-butyric acid odour response in the OB largely disappeared while the isoamyl acetate response did not change. When this experiment was repeated in the presence of 20 mM methyl alpha-D mannopyranoside (a ConA inhibitor), ConA failed to inhibit the n-butyric acid response. Moreover the ConA effect was partially reversible. A Ringer's wash of the OM after ConA treatment, partially restored the OB response to n-butyric acid. Thus the olfactory bulb results seem compatible with the EOG results and reinforce the notion that ConA selectively prevents n-butyric acid sensitive olfactory receptor neurons from firing. Chemical modification of the OM and their effect on OB response patterns may provide a useful approach to investigate olfactory quality coding.     

Biofiltration of n-butyric acid for the control of odour

Odour control from pig production facilities is a significant concern due to increased public awareness and the development of more stringent legislation to control production. Although many technologies exist, biofiltration is still the most attractive due to its low maintenance and operating costs. One of the key odour components, n-butyric acid, was selected for a laboratory scale biofilter study. It was examined as a sole carbon substrate in order to investigate the effectiveness of biofiltration in reducing n-butyric acid concentration under different operating conditions using a moist enriched woodchip medium. Three superficial gas velocities; 38.2, 76.4, and 114.6 m x h(-1) were tested for n-butyric acid concentrations ranging from 0.13 to 3.1 g [n-butyric acid] m(-3) [air]. For superficial gas velocities 38.2, 76.4, and 114.6 m x h(-1), maximum elimination capacities (100% removal) of 148, 113 and 34.4 g x m(3) x h(-1), respectively, were achieved. Upon investigation of effective bed height, true elimination capacities (100% removal) of 230, 233 and 103 g x m(-3) x h(-1), respectively, were achieved at these superficial gas velocities. Averaged pressure drops for superficial gas velocities 38.2, 76.4, and 114.6 m x h(-1) were 30, 78 and 120 Pa, respectively. It was concluded that biofiltration is a viable technology for the removal of n-butyric acid from waste exhaust air, but near 100% removal efficiency is required due to the low odour detection threshold for this gaseous compound.     

Sensitivities of antennal olfactory neurons of the malaria mosquito,Anopheles gambiae,to carboxylic acids

Single sensillum recordings on the antennae of female Anopheles gambiae s.s. mosquitoes revealed neurons sensitive to aliphatic carboxylic acids within (a) subtype(s) sensilla trichodea. The aliphatic acids, acetic acid, propionic acid, butyric acid, iso-butyric acid and iso-valeric acid evoked an inhibition reaction in one of the cell types recorded from. A different cell type was excited in response to the former aliphatic acids, but showed a broader range of sensitivity, as acids with a longer carbon chain length, like caproic acid, elicited excitations as well. In addition, occasionally 1-octen-3-ol elicited an excitation reaction. This article focuses on the carboxylic acid inhibited cell type and its temporal pattern of response to different doses of the compounds. Furthermore, in order to compare the stimulatory effectiveness of the compounds on a per molecule basis, corrections were made for differences in volatility by determining the absolute number of molecules in the stimulus puff.     

Effect of solids retention time and temperature on waste activated sludge hydrolysis and short-chain fatty acids accumulation under alkaline conditions in continuous-flow reactors

The effects of solids retention time (SRT) and temperature on waste activated sludge (WAS) hydrolysis and short-chain fatty acids (SCFAs) accumulation were investigated in a series of continuous-flow reactors at pH 10. The experimental results showed that the increase of either SRT or temperature benefited the hydrolysis of WAS and the production of SCFAs. The changes in SRT gave also impact on the percentage of acetic and propionic acids in the fermentative SCFAs, but little influence on that of the slightly long-chain SCFAs, such as n-butyric, iso-butyric, n-valeric and iso-valeric acids. Compared with the control (pH unadjusted) experiment, at SRT of 12d and temperature of 20 degrees C the concentration of SCFAs produced at pH 10 increased from 261.2 to 933.5mg COD/L, and the propionic acid percentage improved from 11.7 to 16.0%. It can be concluded from this investigation that the efficient continuous production of SCFAs at pH 10 is feasible.     

Responsiveness of the olfactory receptor cells in dog to some odors

A preparation has been developed in the dog which allows recording the electrical activity from an olfactory nerve twig containing the axons of a small group of olfactory receptor cells. The dog's response to n-pentyl acetate is vigorous and stable, like that of other air-breathing animals. The dog's response magnitude dependence on the nasal flow rate was noticeable for n-pentyl acetates, but not so great as for n-butyric acid. The response to n-butyric acid strongly depends on the nasal flow. The start of the nasal air flow caused an increase of neural activity, which is called flow response. The results show that the nasal flow rate is a very important factor which determines the response to odors. Methyl p-hydroxybenzoate is known as a dog's pheromone, however, this odor caused the feeble response in the electrical activity of the dog's olfactory receptor cells. The differences may be dependent on several factors.     

Intraruminal infusion of n-butyric acid induces an increase of ruminal papillae size independent of IGF-1 system in castrated bulls

The objective of this study was to explore morphological alterations of rumen papillae induced by n-butyric acid in relation to the insulin-like growth factor (IGF) system in adult castrated bulls. Three animals fitted with rumen cannula were fed twice daily at a low and high nutritional level (LL and HL), i.e., at 1.1 x maintenance (M) and 1.6 x M, respectively. Diets contained artificial dried grass and concentrate (74:26 and 52:48). Bulls received no (B0) or daily intraruminal infusions of 500 g n-butyric acid (B500) over 14 d. The infusion started 1 h after the morning feeding (9:00) and lasted for 3.5 h. Thus, four treatments (BOLL, B500LL, BOHL, and B500HL) were compared. Blood and rumen mucosa samples from the atrium ruminis were taken at the last day of each period. Length, width and surface of rumen papillae were greater (p < 0.001) in BOHL than in BOLL. Treatment with n-butyric acid resulted in an increase of the papillae surface of 20-40% (p = 0.047) for both nutritional levels as compared to periods without n-butyric acid treatments. The higher nutritional level and intraruminal n-butyric acid infusion induced epithelial cell death. The percentage of proliferative cells was doubled by n-butyric acid treatment. The mRNA of IGF-1 and IGF type 1 receptor (IGF-1R), as well as IGF-1R binding capacity were unaffected by butyric acid treatments. The abundance of IGF-1 mRNA tended to be lower (p = 0.1) and IGF-1R abundance was lower (p = 0.03) in response to the HL. The plasma IGF-1 concentration was lower with butyric acid treatment (p < 0.01), but was unaffected by the nutritional level. In conclusion, under described experimental preconditions of daily short-time intraruminal n-butyric acid infusion alterations of rumen papillae morphology is not mediated by ruminal IGF type 1 receptor and by local IGF-1 expression in papillae in castrated bulls.     

Intraruminal infusion of n-butyric acid induces an increase of ruminal papillae size independent of IGF-1 system in castrated bulls

Abstract

The objective of this study was to explore morphological alterations of rumen papillae induced by n-butyric acid in relation to the insulin-like growth factor (IGF) system in adult castrated bulls. Three animals fitted with rumen cannula were fed twice daily at a low and high nutritional level (LL and HL), i.e., at 1.1 × maintenance (M) and 1.6 × M, respectively. Diets contained artificial dried grass and concentrate (74:26 and 52:48). Bulls received no (B0) or daily intraruminal infusions of 500 g n-butyric acid (B500) over 14 d. The infusion started 1 h after the morning feeding (9:00) and lasted for 3.5 h. Thus, four treatments (B0LL, B500LL, B0HL, and B500HL) were compared. Blood and rumen mucosa samples from the atrium ruminis were taken at the last day of each period. Length, width and surface of rumen papillae were greater (p < 0.001) in B0HL than in B0LL. Treatment with n-butyric acid resulted in an increase of the papillae surface of 20 – 40% (p = 0.047) for both nutritional levels as compared to periods without n-butyric acid treatments. The higher nutritional level and intraruminal n-butyric acid infusion induced epithelial cell death. The percentage of proliferative cells was doubled by n-butyric acid treatment. The mRNA of IGF-1 and IGF type 1 receptor (IGF-1R), as well as IGF-1R binding capacity were unaffected by butyric acid treatments. The abundance of IGF-1 mRNA tended to be lower (p = 0.1) and IGF-1R abundance was lower (p = 0.03) in response to the HL. The plasma IGF-1 concentration was lower with butyric acid treatment (p < 0.01), but was unaffected by the nutritional level. In conclusion, under described experimental preconditions of daily short-time intraruminal n-butyric acid infusion alterations of rumen papillae morphology is not mediated by ruminal IGF type 1 receptor and by local IGF-1 expression in papillae in castrated bulls.     

Dexamethasone inhibition of DMSO-induced transglutaminase activity and differentiation of leukemic cells

Treatment of the Friend erythroleukemic (FL) cell line GM979 with dimethyl sulfoxide (DMSO) or n-butyric acid induced erythroid differentiation. Transglutaminase (TGase) activity also increased in these treated cells. Glucocortical steroids, i.e., dexamethasone (DEX) and triamcinolone acetonide, when added to the cultured medium, inhibited the DMSO-induced hemoglobin synthesis but not n-butyric acid-induced hemoglobin synthesis. Similarly, these steroids inhibited DMSO-increased TGase activity but not n-butyric acid-increased TGase activity in intact FL cells. Neither the differentiation-inducing agents nor the steroids had any effect on TGase activity when they were directly added to cell lysates. These results support the view that the increase of TGase activity may be related to erythroid differentiation of FL cells and of its possible role of this enzyme in FL cell-induced differentiation.     

弱酸（盐）对植物乳杆菌耐酸性的影响

目的探讨弱酸（盐）对植物乳杆菌耐酸性的影响。方法在植物乳杆菌发酵过程中,添加50mmol／L乙酸、10mmol／L丙酸、20mmol／L正丁酸、50mmol／L乙酸钾及2mmol/L柠檬酸钾。结果添加剂量均可使植物乳杆菌耐酸性得到较大的提高,在pH2、37℃下90min,细胞残存率都较对照提高80倍以上,尤以乙酸（盐）、正丁酸为好,而三聚磷酸钾则对细胞耐酸性提高具有较小的作用,细胞残存率较对照约提高5倍。结论在发酵培养基中添加弱酸（乙酸、丙酸及正丁酸）或弱酸盐（乙酸钾、柠檬酸钾及三聚磷酸钾）均可不同程度地提高植物乳扦菌细胞耐酸性。     

Auxin response, but not its polar transport, plays a role in hydrotropism of Arabidopsis roots

Plants are sessile in nature, and need to detect and respond to many environmental cues in order to regulate their growth and orientation. Indeed, plants sense numerous environmental cues and respond via appropriate tropisms, and it is widely accepted that auxin plays an important role in these responses. Recent analyses using Arabidopsis have emphasized the importance of polar auxin transport and differential auxin responses to gravitropism. Even so, the involvement of auxin in hydrotropism remains unclear. To clarify whether or not auxin is involved in the hydrotropic response, Arabidopsis seedlings were treated with inhibitors of auxin influx (3-chloro-4-hydroxyphenylacetic acid), efflux (1-naphthylphthalemic acid and 2,3,5-triiodobenzoic acid), and response (p-chlorophenoxyisobutylacetic acid), and their effects were examined on both hydrotropic and gravitropic responses. In agreement with previous reports, gravitropism was inhibited by all the chemicals tested. By contrast, only an inhibitor of the auxin response (p-chlorophenoxyisobutylacetic acid) reduced hydrotropism, whereas inhibitors for influx or efflux of auxin had no effect. These results suggest that auxin response, apart from its polar transport, plays a definite role in hydrotropic response, and will evoke a new concept for the auxin-mediated regulation of tropisms.     

Induction by short-chain fatty acids of alkaline phosphatase activity in cultured mammalian cells.

Short-chain fatty acids, such as propionic, n-butyric, n-butyric, n-valeric, isovaleric, n-caproic, and n-caprylic acids, induce alkaline phosphatase activity in cultured mammalian cells. Long-chain fatty acids have no similar effects. With B-6 cells (mouse X Chinese hamster cell hybrids), n-butyrate at 2 to 5 mM exhibits the greatest activity. Induction begins exponentially about 24 hours after addition of the fatty acid and continues over 48 hours. Studies on the inducing activity-structure relationship revealed the necessity of a carboxyl and an ethyl or longer alkyl group. n-Butyrate shows a marked synergistic action of induction when added along with other types of inducers: adenosine 3':5'-cyclic monophosphate (cAMP) or 5-bromodeoxyuridine (BrdU). Treatment of other cell lines with either n-buryrate, cAMP, or BrdU revealed a cell-type specific response pattern of alkaline phosphatase. The biological significance of this effect of short-chain fatty acids is discussed.     

Electrophysiological studies of olfaction in the whip spider Phrynus parvulus (Arachnida, Amblypygi)

The olfactory response of the whip spider Phrynus parvulus from Costa Rica was examined using a technique analogous to that used for insect electroantennograms on the tarsi of the antenniform legs which bear multiporous sensilla. Responses to 42 chemicals representing different chain lengths of alkanes, carboxylic acids, alcohols, aldehydes, and ketones, as well as some esters, monoterpenes, and phenolics were examined. Fifty-four percent of the chemicals tested elicited responses. Concentration-response curves were generated for guaiacol, hexanal, methyl salicylate, benzaldehyde, octanoic acid, and linalool. Guaiacol, benzaldehyde, and hexanol elicited the greatest responses and no differences were detected between the sexes. Compounds with chain lengths of six carbon atoms generated strong responses and most monocarboxylic acids and ring compounds elicited responses. Some compounds produced increases in potential believed to arise from a hyperpolarizing effect on the neurons. The broad spectrum of chemicals to which these animals respond is similar to results of other studies examining the general olfactory sense of insects. It is possible that odor learning plays a significant role in the behavior of amblypygids.     

Antagonistic interaction between systemic acquired resistance and the abscisic acid-mediated abiotic stress response in Arabidopsis

Systemic acquired resistance (SAR) is a potent innate immunity system in plants that is effective against a broad range of pathogens. SAR development in dicotyledonous plants, such as tobacco (Nicotiana tabacum) and Arabidopsis thaliana, is mediated by salicylic acid (SA). Here, using two types of SAR-inducing chemicals, 1,2-benzisothiazol-3(2H)-one1,1-dioxide and benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester, which act upstream and downstream of SA in the SAR signaling pathway, respectively, we show that treatment with abscisic acid (ABA) suppresses the induction of SAR in Arabidopsis. In an analysis using several mutants in combination with these chemicals, treatment with ABA suppressed SAR induction by inhibiting the pathway both upstream and downstream of SA, independently of the jasmonic acid/ethylene-mediated signaling pathway. Suppression of SAR induction by the NaCl-activated environmental stress response proved to be ABA dependent. Conversely, the activation of SAR suppressed the expression of ABA biosynthesis-related and ABA-responsive genes, in which the NPR1 protein or signaling downstream of NPR1 appears to contribute. Therefore, our data have revealed that antagonistic crosstalk occurs at multiple steps between the SA-mediated signaling of SAR induction and the ABA-mediated signaling of environmental stress responses.     

Olfactory response and resource utilization in Drosophila: interspecific comparisons

Olfactory response and resource utilization in Drosophila were compared among three domestic (D. melanogaster, D. simulans, D. immigrans) and one Australian endemic (D. lativittata) species. Olfactory response was measured in a choice type olfactometer (Fuyama, 1976). The following chemicals common in Drosophila resources were used as odourants: acetaldehyde, acetic acid, propionic acid, methanol, ethanol, n-propanol, isopropanol, n-butanol. Resource status of these chemicals was determined either from the literature or by adult longevity tests.
All species were attracted by acetaldehyde, while methanol, isopropanol and n-butanol were unattractive. Ethanol attracted all species except D. immigrans , while only D. lativittata and D. melanogaster were attracted to n-propanol, propionic acid and acetic acid
Methanol and isopropanol were not utilized as resources by any of the species, while D. melanogaster and D. lativittata showed greater utilization/tolerance of the other chemicals. Some correlation between resource utilization and olfactory response was found at the interspecific level, although not all chemicals utilized as resources are attractants. The adaptive significance of the interspecific variation in olfactory response is discussed, especially in relation to habitats selected. The results provide suggestions for habitat selection studies at the intraspecific level.     

An inter-laboratory collaborative study by the Non-Genotoxic Carcinogen Study Group in Japan, on a cell transformation assay for tumour promoters using Bhas 42 cells

The Bhas promotion assay is a cell culture transformation assay designed as a sensitive and economical method for detecting the tumour-promoting activities of chemicals. In order to validate the transferability and applicability of this assay, an inter-laboratory collaborative study was conducted with the participation of 14 laboratories. After confirmation that these laboratories could obtain positive results with two tumour promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA) and lithocholic acid (LCA), 12 coded chemicals were assayed. Each chemical was tested in four laboratories. For eight chemicals, all four laboratories obtained consistent results, and for two of the other four chemicals, only one of the four laboratories showed inconsistent results. Thus, the rate of consistency was high. During the study, several issues were raised, each of which were analysed step-by-step, leading to revision of the protocol of the original assay. Among these issues were the importance of careful maintenance of mother cultures and the adoption of test concentrations for toxic chemicals. In addition, it is suggested that three different types of chemicals show positive promoting activity in the assay. Those designated as T-type induced extreme growth enhancement, and included TPA, mezerein, PDD and insulin. LCA and okadaic acid belonged to the L-type category, in which transformed foci were induced at concentrations showing growth-inhibition. In contrast, M-type chemicals, progesterone, catechol and sodium saccharin, induced foci at concentrations with little or slight growth inhibition. The fact that different types of chemicals similarly induce transformed foci in the Bhas promotion assay may provide clues for elucidating mechanisms of tumour promotion.     

小鼠肠道菌群代谢产物与糖尿病的相关性研究

目的研究糖尿病小鼠粪便中肠道菌群代谢产物与血糖之间的相关性,探讨肠道菌群与糖尿病之间的关系。方法采用高脂饮料喂养加腹腔注射链脲佐菌素(STZ)的方法建立糖尿病小鼠模型;将实验动物随机分为正常组、高脂组、糖尿病组及模型给药组,连续给药5周后,采血测血糖血脂,同步收集动物粪便,测粪便中短链脂肪酸(Short-chain fatty acids,SCFA)及D-乳酸。SCFA的检测使用气相色谱法,D-乳酸的检测使用紫外酶促法。结果糖尿病组小鼠粪便中乙酸、丙酸和正丁酸含量明显低于正常组及高脂组(P<0.01),D-乳酸含量明显高于正常组及高脂组(P<0.01);给药组乙酸、丙酸和正丁酸含量明显高于糖尿病组(P<0.01),D-乳酸含量明显低于糖尿病组(P<0.01)。给药组丙酸、正丁酸的含量与正常组间差异无统计学意义(P>0.05),但乙酸的含量仍低于正常组(P<0.01),D-乳酸的含量仍高于正常组(P<0.01)。结论糖尿病小鼠粪便中的肠道菌群代谢产物与血糖之间存在着密切的关系,代谢产物的差异性,提示肠道菌群的差异性,反映出糖尿病小鼠存在肠道菌群紊乱。