1-Butaneboronic acid binding to Aeromonas proteolytica aminopeptidase: a case of arrested development.

Hydrolases containing two metal ions connected by a bridging ligand catalyze reactions important in carcinogensis, tissue repair, post-translational modification, control and regulation of biochemical pathways, and protein degradation. The aminopeptidase from Aeromonas proteolytica serves as a paradigm for the study of such bridged bimetallic proteases since its three-dimensional structure is known to very high resolution and its catalytic reaction is amenable to spectroscopic examination. Herein, we report the X-ray crystal structure at 1.9 A resolution of AAP complexed with 1-butaneboronic acid (BuBA). This structure suggests that this complex represents a snapshot of the proteolytic reaction in an arrested form between the Michaelis complex and the transition state. Comparison of the structure with spectroscopic and other data allows us to conclude that the apparently structurally symmetrical dizinc site is actually asymmetric electrostatically.

Reliability of a food frequency questionnaire to assess dietary antioxidant intake.

OBJECTIVE: Epidemiologic evidence of a role for antioxidants in the prevention of chronic disease has been inconclusive, in part due to the difficulty of measuring past diets of free-living populations. The purpose of the current study was to examine the reliability of a 19-item, self-administered, semiquantitative, food frequency questionnaire to assess intake of the major dietary antioxidants. METHODS: Reliability was established by administering the food frequency questionnaire a second time by telephone. The subjects comprised 151 participants in the Melbourne Visual Impairment Project, a study of the distribution and determinants of eye disease in Melbourne residents aged 40 and over. RESULTS: Spearman correlation coefficients ranged from 0.39 for spinach to 0.76 for yoghurt, and all were highly significant (all p = 0.001). The reliability of the instrument was not influenced by gender, English speaking ability, or the number of days between the first and second administration of the questionnaire. CONCLUSION: In conclusion, we have shown this 19-item food frequency questionnaire to be highly reliable. It should be useful for anyone involved in the study of the relationship of dietary antioxidant intake to health outcomes in large populations where limitations of time and money prohibit the collection of more detailed dietary intake information.

Knowledge of glaucoma, and its relationship to self-care practices, in a population sample.

OBJECTIVE: To determine the level of knowledge of glaucoma in a population-based sample, and its relationship to self-care practices. DESIGN AND SUBJECTS: A cluster random sample of the Melbourne population 40 years of age and older was interviewed. One thousand seven hundred and eleven residents living in five randomly selected Melbourne metropolitan suburbs, each consisting of two adjacent census collector districts. MEASURES: Questions were asked concerning respondents' awareness, knowledge and description of the disease. Respondents were also asked the year of their last visit to their eye health care provider. RESULTS: Seventy per cent of the sample had heard of glaucoma. However, only 22% provided a description that demonstrated a reasonable understanding of the disease. A lack of awareness and knowledge of glaucoma appeared to be negatively related to self-care practices. CONCLUSION: Serious deficiencies in the basic knowledge of glaucoma in the community was demonstrated. This has significant public health implications as only a small percentage of the at-risk population may present themselves for assessment and treatment. Informing the community about glaucoma is an important step in promoting preventative ophthalmic care and reducing visual impairment and blindness.

Esters of 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-endo-ol with antiarrhythmic and other activities.

The synthesis of esters derived from 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-endo-ol, obtained by LiAlH4 reduction of 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-one, is described. Some of these esters showed an appreciable antiarrhythmic activity in rats, as well as moderate hypotensive and local anesthetic activities in rats and mice, respectively.

3,5-Diphenyl-1H-pyrazole derivatives. VI--Esters and 2-dialkylaminoethyl ethers of 1(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole and N,N-disubstituted 1-(2-amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles with depressant and platelet antiaggregating activities.

The syntheses of 1-(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole 1 by reaction of 2-hydrazino-1-phenylethanol with dibenzoylmethane, of esters 2 and 2-dialkylaminoethyl ethers 3 starting from 1 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N,N-disubstituted 1-(2-amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles 5 by reaction of secondary amines with the tosylate of 1, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats.

Prenatal and postnatal vanadium exposure in rats: effect on vasomotor reactivity development of pups.

The study has been carried out on albino rats pre and/or postnatally exposed to vanadate (1 and 10 mg/dl). In pups pre- and postnatal or postnatal vanadate exposure significantly decreased on the 30th and 60th day of age the pressor response to 1-noradrenaline, and increased the pressor response to sinus-carotid baroreceptor stimulation and the hypotensive responses to 1-isoprenaline and acetylcholine. The effects were observed at vanadate doses that did not interfere with gestation, maternal and pup body weight, maternal systolic arterial blood pressure during pregnancy, and pup systolic arterial blood pressure. These doses have not determined any macroscopic teratogenic effects.

Interference of prenatal and postnatal exposure to Ca2+-antagonist agents on rat functional development of vascular system.

Exposure to drugs during pregnancy can alter functional development of the vascular system. The present investigation was carried out in order to evaluate the effects of prenatal and postnatal exposure to Ca2+-antagonist (diltiazem, verapamil, and nimodipine) drugs on the development of rat vasomotor reactivity. Studies were carried out on pregnant female albino rats exposed from the first day of pregnancy until weaning to diltiazem and verapamil (6 and 24 mg/kg in their drinking water ad libitum) and nimodipine (3 and 12 mg/kg in their food ad libitum). After weaning, pups were exposed until the 60th day of age to the same treatment as their mothers were. Afterwards, pups from the 60th to 90th day of age were fed with a normal diet. In 30-, 60-, and 90-day-old conscious and anaesthetized pups, we evaluated the following: 1) systolic arterial blood pressure; 2) vasomotor responses elicited by various agents: L-noradrenaline (0.1, 1, and 5 micrograms/kg IV), L-isoprenaline (0.01, 0.1, and 1 micrograms/kg IV), and acetylcholine (0.01, 0.1, and 1 micrograms/kg IV) and by sinus-carotid baroreceptor stimulation; and 3) catecholamine, acetylcholinesterase, and adenosinase plasma levels. Prenatal and postnatal exposure to Ca2+-antagonist drugs significantly (P less than .05) decreased the pressor response to sinus-carotid baroreceptor stimulation and to L-noradrenaline and increased the hypotensive responses to L-isoprenaline and acetylcholine. Moreover, this type of treatment, although it induced a significant (P less than .05) decrease of catecholamine plasma levels, did not modify the acetylcholinesterase and adenosinase plasma levels in 30- and 60-day-old rats. On the 90th day of age, the evaluated parameters were not different from those of control rats. Our results showed that exposure to Ca2+ antagonists during pregnancy and the postnatal period may alter the functional development of rat vasomotor reactivity.

Pharmacodynamic profile of fenoverine, a novel modulator of smooth muscle motility.

Experimental research has documented that fenoverine is a depressant drug mostly active on the intestinal smooth muscle; however, it is also active on other tissues as well as on the genito-urinary tract. Fenoverine may be considered a synchronizer of smooth muscle effective in modulating the intracellular influx of calcium into the cell and its release from the intracellular pool. Fenoverine causes a reduction of the excitatory junction potential (EJP) in intestinal smooth muscle by stimulating parasympathetic efferent fibres without any change in the inhibitory junction potential (IJP). This also occurs in the presence of atropine. Fenoverine reduces the intracellular Ca2+ concentration by decreasing the calcium gradient across the cell membrane, as well as decreasing the release of Ca2+ from the intestinal pool more intensely than papaverine (but less intensely than nifedipine, verapamil or diltiazem). This phenomenon has been observed in the intestinal smooth muscle and also in the genito-urinary tract.