Quantitative Detection of 15 Serum Bile Acid Metabolic Products by LC/MS/MS in the Diagnosis of Primary Biliary Cholangitis

To determine 15 bile acid metabolic products in human serum by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and value their diagnostic outcome in primary biliary cholangitis (PBC). Serum from 20 healthy controls and 26 patients with PBC were collected and went LC/MS/MS analysis of 15 bile acid metabolic products. The test results were analyzed by bile acid metabolomics, and the potential biomarkers were screened and their diagnostic performance was judged by statistical methods such as principal component and partial least squares discriminant analysis and area under curve (AUC). 8 differential metabolites can be screened out: Deoxycholic acid (DCA), Glycine deoxycholic acid (GDCA), Lithocholic acid (LCA), Glycine ursodeoxycholic acid (GUDCA), Taurolithocholic acid (TLCA), Tauroursodeoxycholic acid (TUDCA), Taurodeoxycholic acid (TDCA), Glycine chenodeoxycholic acid (GCDCA). The performance of the biomarkers was evaluated by the AUC, specificity and sensitivity. In conclusion, DCA, GDCA, LCA, GUDCA, TLCA, TUDCA, TDCA and GCDCA were identified as eight potential biomarkers to distinguish between healthy people and PBC patients by multivariate statistical analysis, which provided reliable experimental basis for clinical practice.     

Chirality differences in amino acid retention and release from the acid-extractable pool of cultured mammalian cells

In previous work, no chiral differences were found between D and L enantiomers of Leu in their ability to displace one another from the acid-extractable pool in mammalian cells. Recent evidence suggested otherwise. Our aim is to examine whether, in physiological range, D-amino acids have an equivalent ability to displace L-amino acids from the acid-extractable pool of HeLa cells, and vice versa. In the millimolar range, D-Leu and L-Leu have similar uptake and displacement properties with regard to the acid-extractable pool in HeLa cells, despite only the latter isomer being incorporated into protein. Below millimolar concentrations however, a distinct difference was found in the displacement of tritium-labelled L-Leu from the pool by unlabelled D-Leu compared with unlabelled L-Leu. Thus, unlabelled L-Leu in the external medium at 10⁻⁴ or 10⁻⁵ M displaced an equivalent amount of label from the pool as D-Leu introduced at a concentration approx. one order of magnitude higher, respectively. Reciprocal experiments, in which the acid-extractable pool was preloaded with ³H-D-Leu, confirmed this finding. The chirality difference was noted whether pool prelabelling was carried out at 37 or 0°C; but in order to avoid the complications of active transport mechanisms, the competition work reported here was done at 0°C. Similar chirality differences were observed with other hydrophobic amino acids, including His, Ile and Phe, such as, preferential displacement by the L-Leu racemer compared with the D-Leu racemer below mM levels. This was also true for the D and L forms of the non-utilisable isomer of Leu, norleucine (nLeu). We conclude that D-forms of hydrophobic amino acids have lower affinity for similar or the same intracellular binding sites involved in the acid-extractable pool than their L-forms. The significance of these chirality findings to amino acid pools in cells, and to the predominance of L-forms of amino acids in the biosphere is considered.     

Flowering seasonality and flower characteristics ofLoranthus acaciae Zucc. (Loranthaceae): Implications for advertisement and bird-pollination

The flowering biology and pollination ecology ofLoranthus acaciae was studied at Hazeva in the northern Arava Valley in Israel. Flowers at anthesis had red anthers, a red stigma and a green corolla which turned red as a postfloral phenomenon. Their flowering period was approximately 10 months long (from mid-June until mid-April) during which time two main flowering patterns were distinguished. Some plants flowered twice a year, with separate summer and winter flowering periods; other plants flowered continuously, with two peaks, one in the summer and one in the winter. Several significant differences between summer and winter flowering and fruiting were found: (1) the summer flowering period was shorter than that of winter, (2) flowering synchrony between individual plants was lower in summer than in winter, (3) in summer the plants produced a larger proportion of female flowers, whereas in winter most of the plants produced a larger proportion of hermaphrodites, (4) in summer a limited number of plants produced smaller flowers while the majority produced normal-sized flowers, whereas in winter the entire population produced only normal-sized flowers, and (5) fruit set percentage was lower in summer than in winter.L. acaciae was found to be self-compatible, but, since it was not spontaneously self-pollinated, it showed high dependence on pollinator activity. In summer the flowers were visited by a wide spectrum of pollinators, both birds and insects, while in winter flowers were visited almost exclusively by the orange-tufted sunbird (Nectarinia osea osea, Nectariniidae). These seasonal changes in flowering characteristics and pollinator activity could explain why reproductive success is higher in winter than in summer.     

Response of hepatic function to hepatic copper deposition in rats fed a diet containing copper

Fischer rats were a fed diet supplied with copper chloride (150–600 ppm) for 60 d from weaning. Serum (glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) activities were increased with the increase of Cu concentration in the diet. Biliary excretion of Cu was related to the dietary Cu level. Depositions of hepatic and renal Cu were also related to the dietary Cu level in a dose-dependent manner. In particular, hepatic (155.2±13.3 μg/g) and renal (44.9±4.4 μg/g) Cu concentrations increased abruptly in the Cu-600 ppm group. In the liver, about 60% of Cu was distributed in the soluble fraction (100,000 g supernatant). In the Cu-600 ppm group, 25% of cystosolic Cu was bound to metallothionein (MT). Our results suggest that chronic exposure to Cu appears to have a deleterious effect on the hepatic function, and further, that even in rats with normal biliary Cu excretion, clearance of Cu from the liver may be marginal when dietary Cu is near the 600-ppm level. Although Cu is an essential nutrient, an overload of Cu should be avoided.     

Properties of monovalent nickel complexes with tetraaza-macrocyclic ligands in aqueous solutions

The effects of N-alkylation on the redox potential of the couples NiLⁱ²⁺/NiLⁱ⁺, L = tetraaza-14-membered-macrocyclic ligands, and on the properties of the monovalent nickel complexes in aqueous solutions are reported for 14 complexes. The spectra and lifetimes of the NiLⁱ⁺ complexes are reported. The self-exchange rates for the couples NiLⁱ²⁺/NiLⁱ⁺ were determined. Two of the ligands were synthesized for the first time for this study. Cyclic voltammetry and pulse radiolysis were used. The results point out that: (i) N-alkylation always shifts the redox potential to a less cathodic one; this effect stems to a large degree from the decrease in the solvation energy of the complex caused by the N-alkylation of the ligand. (ii). The lifetime of the monovalent complexes is not linearly related to the redox potential of the NiLⁱ²⁺/NiLⁱ⁺ couples. (iii) The NiLⁱ⁺ complexes exist in several isomeric forms; the rate of the isomerization depends on the structure of the ligand. (iv) Different isomers of NiLⁱ⁺ may be formed when the complex NiLⁱ²⁺ is reduced by different reagents; therefore, the pulse-radiolytically formed NiLⁱ⁺ complexes might have different properties than those formed electrochemically.     

Two New Species of Aphelenchoididae (Nemata) from Declining Red Pines in Maryland

Aphelenchoides resinosi n. sp. and Ektaphelenchus joyceae n. sp. are described and illustrated from red pines of the Allegheny plateau of Maryland, USA. The new species were found in trees infested with Bursaphelenchus xylophilus. Primary diagnostic characters of A. resinosi females are constriction of the head, basal stylet knobs, tong postuterine sac, two incisures in the lateral field, and conical tail four to five anal body widths long with a simple terminal mucro. Diagnostic characters of the males are two pairs of subventral caudal papillae and spicule shape: Primary diagnostic characters of E. joyceae females are a slight constriction of the head, six similar lips, conical tail, and short postuterine sac. Diagnostic characters of the males are spicule size and shape, a single row of spermatocytes, and one pair of caudal papillae. Within-tree distributions of A. resinosi and E. joyceae are presented. A total of 70% of both red-needled and chlorotic-needled trees in the study were positive for A. resinosi and E. joyceae. Branch hierarchy was related to the percentage of samples positive for A. resinosi.     

Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage.

OBJECTIVE: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. DESIGN: Randomised clinical trial. SETTING: University hospital. SUBJECTS: 32 patients with cirrhotic portal hypertension. INTERVENTIONS: Programmed injection sclerotherapy with subcutaneous octreotide 50 micrograms twice daily for 6 months, or programmed injection sclerotherapy alone. MAIN OUTCOME MEASURES: Episodes of recurrent variceal bleeding and survival. RESULTS: Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 v 7/16; P = 0.037, Fisher''s exact test), and their survival was significantly improved (P < 0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease -6.0 mm Hg, interquartile range -10 to -4.75 mm Hg, P = 0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. CONCLUSION: Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension.     

Vasomotor instability preceding tilt-induced syncope: does respiration play a role?

Lipsitz, Lewis A., Raymond Morin, Margaret Gagnon, DanKiely, and Aharon Medina. Vasomotor instability precedingtilt-induced syncope: does respiration play a role? J. Appl. Physiol. 83(2): 383-390, 1997.This studyaimed to determine whether alterations in cardiovascular dynamicsbefore syncope are related to changes in spontaneous respiration.Fifty-two healthy subjects underwent continuous heart rate (HR),arterial blood pressure (BP), and respiratory measurements during10-min periods of spontaneous and paced breathing (0.25 Hz) in thesupine and 60° head-up tilt positions. Data were evaluated by powerspectrum and transfer function analyses. During tilt, 27 subjectsdeveloped syncope or presyncope and 25 remained asymptomatic. Subjectswith tilt-induced syncope had significantly greater increases inlow-frequency (0.04-0.15 Hz) systolic BP, diastolic BP, and HRpower during tilt than the asymptomatic subjects(P  0.01). This difference waspresent during spontaneous but not paced breathing. However, averagetidal volume, respiratory rate, minute ventilation, proportion ofbreaths below 0.15 Hz, and low-frequency respiratory power during tilt did not differ between syncopal and nonsyncopal subjects. Transfer magnitudes between low-frequency respiration and BP, and between BP andinterbeat interval, were also similar between groups. Thus vasomotorinstability before syncope is not related to alterations in respirationor the cardiovagal baroreflex but may reflect oscillating centralsympathetic outflow to the vasculature.