Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01.

BACKGROUND: It has been recently demonstrated that the ghrelin receptor agonist, HM01, caused defecation in rats that were treated to provide a model for the constipation of Parkinson's disease. HM01 significantly increased fecal output and increased Fos activity in neurons of the hypothalamus and hindbrain, but not in the spinal defecation center. Other ghrelin agonists act on the defecation center. METHODS: Receptor pharmacology was examined in ghrelin receptor (GHSR1a) transfected cells. Anesthetized rats were used to investigate sites and mechanisms of action. KEY RESULTS: HM01 activated rat GHSR1a at nanomolar concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01, intravenous, was potent to activate propulsive colorectal contractions. This was prevented by pelvic nerve section and by intravenous YIL781, but not by spinal cord section rostral to the defecation centers. Direct intrathecal application of HM01 to the defecation center at spinal level L6-S1 initiated propulsive contractions of the colorectum. CONCLUSIONS & INFERENCES: HM01 stimulates GHSR1a receptors on neurons in the lumbosacral defecation centers to cause propulsive contractions and emptying of the colorectum. It has greater potency when given systemically, compared with other GHSR1a agonists.

Comparison between several muscle strength and cardiorespiratory fitness indices with body composition and energy expenditure in obese postmenopausal women.

The purpose of this study was to compare the relationship of several muscle strength and cardiorespiratory fitness indices with body composition and energy expenditure in obese postmenopausal women. This was a cross-sectional study involving 72 obese postmenopausal women (age: 60.0±4.8 years; body mass index: 34.1±3.5 kg/m²). Muscle strength was determined by hand dynamometer and cardiorespiratory fitness was measured by indirect calorimetry. Muscle strength and cardiorespiratory fitness were expressed in absolute (kg and L/min, respectively) and in relative values (kg/body weight (BW) and kg/lean body mass (LBM) for muscle strength and ml/min/kg BW and ml/min kg LBM for cardiorespiratory fitness). Body composition was measured using dual energy x-ray absorptiometry. Anthropometric (waist and thigh circumference), physical activity energy expenditure and daily number of steps (SenseWear armband) as well as blood pressure were also assessed. Correlations of muscle strength and cardiorespiratory fitness indices with body composition and energy expenditure showed several similarities, however, several variations were also observed. Furthermore, our results showed that age and waist circumference were the primary independent predictors for the muscle strength indices, explaining 22-37% of the variance and % body fat and age were the primary predictors for the cardiorespiratory fitness indices, explaining 18-40% of the variance. In conclusion, the present study indicates that the different methods of expressing muscle strength and cardiorespiratory fitness may display several variations and similarities with body composition and energy expenditure associations. Therefore, interpretations of relationships between muscle strength and cardiorespiratory indices with body composition and energy expenditure factors should take in account the method used to express them.

Separation of overlapping spectra from evolving systems using factor analysis. 4. Fluorescence spectra of hematoporphyrin IX.

Fluorescence spectra of hematoporphyrin IX (Hp) in water and in aqueous SDS solutions are obtained in the pH range 0.1 to 13 to determine the ionisation state of the molecule as a function of pH. In water, the spectra are complicated by aggregation which is quite severe near pH 4. In aqueous SDS, the aggregation is much less violent. Factor analysis (FA) is used to identify five species in the fluorescence spectra in each series of solutions. The distribution curve of these species as a function of pH is also obtained. By comparing the spectra and the distribution curve of Hp with those of HPPEEA, an ethanolamide derivative of Hp that does not contain the carboxylic groups (Part 3), the species are identified. For Hp in water we have obtained the following species: the dication in two allotropic forms in the pH range 0 to 5; the monocation (with the charge on an imino nitrogen) in the pH range 2 to 7; and the free base in the pH range 3.5 to 13. The monocation observed by the second derivative technique revealed three subspecies. For Hp in aqueous SDS we have obtained the following species; one dication in the pH range 0 to near 4; one monocation (with the charge on an imino nitrogen) in the pH range 0.5 to 9; three free bases (with no charge on the imino nitrogen) in the pH range 4 to 13. Of the latter, one species is the neutral molecule, another is a dianion (with the charges on the carboxylic side chains), and the third one appearing at pH higher than 10 is an allotropic form of the dianion.

Separation of overlapping spectra from evolving systems using factor analysis. 3. Fluorescence spectra of hematoporphyrin IX di-n-propylether diethanolamide.

Fluorescence spectroscopy of hematoporphyrin IX di-n-propylether diethanolamide (HPPEEA) in aqueous solutions, with and without SDS, was obtained in the pH range from 0.1 to 13. At pH greater than 3, HPPEEA in water solutions gives spectra complicated by aggregation whereas in aqueous SDS solutions, the aggregation is greatly reduced. Factor analysis is used to separate the spectra of the individual species from the experimental spectra. Five and four species are identified in pure water and in aqueous SDS solutions, respectively. The predominant species are: two free bases at pH higher than 6; one monocation at pH near 4; and two or one dications at pH lower than 2.5. The intensity signatures are related to the ionic distribution and to the aggregation situation of HPPEEA at different pH.