Inhibitory action of quercetin on intestinal transit in mice

The effects of quercetin have been investigated on the gastrointestinal propulsion of charcoal meal in mice. Quercetin reduced the rate of intestinal transit and this effect was potentiated by verapamil.     

Inhibition of growth of PC-82 human prostate cancer line xenografts in nude mice by bombesin antagonist RC-3095 or combination of agonist [D-Trp6]-luteinizing hormone-releasing hormone and somatostatin analog RC-160.

The effects of treatment with a bombesin receptor antagonist [D-Tpi6, Leu13 psi (CH2NH) Leu14]BN(6-14)(RC-3095) and the combination of an agonist of luteinizing hormone-releasing hormone [D-Trp6]-LH-RH and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val- Cys-Trp-NH2 (RC-160) were studied in nude mice bearing xenografts of the hormone-dependent human prostate tumor PC-82. During the 5 weeks of treatment, tumor growth was decreased in all treated groups compared with controls. Bombesin antagonist RC-3095 and the combination of [D-Trp6]-LH-RH and RC-160 caused a greater inhibition of tumor growth than [D-Trp6]-LH-RH or RC-160 alone as based on measurement of tumor volume and percentage change in tumor volume. The largest decrease in tumor weight was also seen in the groups treated with the bombesin antagonist and with the combination of RC-160 and [D-Trp6]-LH-RH. Serum prostatic-specific antigen levels were greatly decreased, and insulin-like growth factor I (IGF-I) as well as growth hormone levels were reduced in all treated groups. Specific binding sites for [D-Trp6]-LH-RH, epidermal growth factor (EGF), IGF-I, and somatostatin (SS-14) were found in the tumor membranes. Receptors for EGF were significantly down-regulated by treatment with the bombesin antagonist or RC-160. Combination of LH-RH agonists with somatostatin analog RC-160 might be considered for improvement of hormonal therapy for prostate cancer. The finding that bombesin antagonist RC-3095 inhibits the growth of PC-82 prostate cancer suggests the merit of further studies to evaluate the possible usefulness of antagonists of bombesin in the management of prostatic carcinoma.     

Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5u/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on S-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC₅₀, 0.02 μM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC₅₀,0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E₃ and 10 E₅) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.     

Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with β-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.     

A VIP antagonist distinguishes VIP receptors on spinal cord cells and lymphocytes

Vasoactive intestinal peptide (VIP) is a neuropeptide which also interacts with cells of the immune system. The paucity of specific VIP receptor antagonists has hampered studies of possible receptor heterogeneity and of VIP function. To aid in achieving these goals, a new VIP antagonist, a hybrid between neurotensin and VIP, has been synthesized. This peptide interacted with VIP receptors on spinal cord cells with an affinity 10-fold greater than VIP itself. In contrast, 1000-fold higher concentrations of the antagonist were required to displace labeled VIP from its receptor on lymphoid cells as compared to VIP itself, suggesting VIP receptor heterogeneity between immune and spinal cord cells.     

Clinical status and parasitic infection in a Wichi Aboriginal community in Salta,Argentina

In a study, carried out in 2000, of the clinical and parasitological status of a Wichi Aboriginal community living in the suburbs of Tartagal, northern Salta, Argentina, 154 individuals were screened for parasitic infections. Ninety-five faecal samples were also obtained from the same population. Ninety-three percent of the subjects were positive for 1 or more of the parasites investigated by direct test and 70.5% of them had parasitic superinfection. The most frequent helminths were Strongyloides stercoralis (50.5%) and hookworm (47.4%). We found low reinfection rates and a long reinfection period after treatment and provision of safe water and sanitation. Serum reactivity of these patients was analysed by enzyme-linked immunosorbent assay and indirect immunofluorescent assay and 22.1% of them had anti-Toxocara antibodies, 16.2% were positive for a complex antigen of Leishmania braziliensis, 29.9% were positive for a complex Trypanosoma cruzi antigen, and 17.5% were positive for a specific Trypanosoma cruzi antigen, Ag1 63136/cruzipain.     

Evaluation of computerized analysis of the propagation of human duodenojejunal contractions

Abstract Detection of peristalsis in the human small intestine has been limited in the past by both the available measurement techniques and the complexity of this activity. Recent developments in ambulant recording have provided a means of monitoring the occurrence of intestinal contractions at multiple sites in the small bowel, but the problem of complexity remains. Using digital data recorded from an intra-luminal strain-gauge transducer in the proximal gut, an algorithm was implemented to identify and classify contractile events within the small bowel. By modelling propagated activity the effect of varying transducer spacing and the number of transducers used was assessed. The question of variability of apparent velocity of peristaltic contractions was examined using successive cross-correlation calculations to extract underlying phase differences between samples of 512 minutes of manometric recording over 150 mm of human small bowel. The effective velocity was found to have a median value of 14 mm sec^-1 and an inter quartile range of 12–18 mm see^-1). It is proposed that, in dynamically tracking variations in phase difference between adjacent recording sites, cross-correlation techniques should be used to control the parameters used for the recognition of propagated contractile events and thereby improve the specificity of this process.     

CGRP免疫反应神经纤维在大鼠胆总管与十二指肠连接处的分布

用免疫组织化学ＡＢＣ法，研究了降钙素基因相关肽（ＣＧＲＰ）免疫反应神经纤维在大鼠胆总管末端与十二指肠连接处的分布。大鼠的胆总管末端有较丰富的ＣＧＲＰ免疫反应神经纤维，它们多呈串珠（膨体）状，少数为无膨体的细长纤维。ＣＧＲＰ－ＩＲ纤维主要分布肌层及血管周围，在神经纤维的附近可见到含ＣＧＲＰ－ＩＲ阳性颗粒的肥大细胞。本实验为神经免疫调节机制的研究提供了形态学依据。     

Urinary excretion of acid-soluble peptides in children with Duchenne muscular dystrophy

In order to investigate the validity of the hypothesis that acid-soluble peptides (ASP) in urinary excreta can be applied as an index of the protein catabolism of the whole body, we measured the urinary excretion of ASP in 46 normal children and in 18 children with Duchenne muscular dystrophy (DMD), in which continuous breakdown of skeletal muscle protein is presumed. The mean value of ASP in the children with DMD was significantly higher than that in normal controls. The concentration of ASP was correlated with that of 3-methylhistidine (3MH), which has been proposed as an index of muscle breakdown. This finding indicates that urinary ASP reflects the catabolism of body proteins. No correlation was observed between the concentration of ASP and that of 1-methylhistidine (1MH), which is used as an objective index of meat and fish ingestion. After the administration of bestatin, an inhibitor of leucine aminopeptidase, for 9 months, the urinary ASP concentration of children with DMD increased markedly. This increase is thought to have been directly caused by the bestatin itself. Urinary ASP is therefore apparently a more conveniently applied index of protein catabolism than is urinary 3MH, which requires the application of several restrictions. However, it should not be applied when the effect of bestatin administration is evident.