Gastrointestinal stromal tumor in ileal neobladder

Abstract  Gastrointestinal stromal tumor (GIST) is a recently described mesenchymal tumor that can develop in any portion of the gastrointestinal tract. The occurrence of a GIST in the urinary tract is rare, but GIST can present as tumor of the urinary tract or invade the urinary tract. This is the first reported case of GIST in the ileal neobladder, which presented as a submucosal tumor. The patient underwent an open exploration and partial resection of the neobladder pouch.     

A型肉毒毒素对离体豚鼠心脏的抑制作用

本实验用Langendorff法,在恒温、恒液压(灌流压)和供给足够氧气的条件下,对豚鼠(Cavin porcellus)离体心脏进行灌流,以心肌收缩力、心跳频率、心电图和冠脉流量为观察指标,对照观察A型肉毒毒素对心脏活动的影响。结果发现:A型肉毒毒素可使(1)心肌收缩力减弱;(2)心跳频率减慢,甚至停搏;(3)冠脉流量减少;(4)心电图有异常改变,显示对心脏起搏有阻遏现象.     

豚鼠胃肠道粘膜下层内神经节丛与血管的伴行现象

对豚鼠胃肠道各段的研究发现,在胃体、胃底和幽门的粘膜下层内,血管仅由神经纤维束伴行。除小肠粘膜下层可见神经节丛与血管伴行外,在盲肠粘膜下层,亦可见神经节丛与小动、静脉伴行,尤以血管始段及第一分支段最明显。某些神经节丛还发出神经纤维束投射到血管壁上。在结肠和直肠均未见到神经节丛与血管的伴行现象。     

Synthesis and biological activity of Substance P C-terminal hexapeptide and heptapeptide analogues

The analogues [Glu(OBzl)¹¹]SP_6–11 and [Glu(OBzl)¹¹]SP_5–11 of the C-terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the SCH₃ group of Met¹¹ is replaced by the COOCH₂C₆H₅ group. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD), and rat portal vein (RPV). The selectivity for the different receptors has been studied by utilizing atropine-treated guinea pig ileum (GPI + At). The results showed that both analogues are mainly active on GPI through the NK-1 receptor and that both analogues are equipotent to Substance P.     

Characterisation of pre- and post-synaptic α-adrenoceptors in modulation of the rat ileum longitudinal and circular muscle activities

Previous study has shown that α_2D-adrenoceptors are involved in modulation of peristalsis in the rat ileum. The aim of the present study was to determine the tissue location of α-adrenoceptors in the rat ileum by using a recently devised method. The pre-synaptic α-adrenoceptors were characterised by measuring the potencies of agonists to inhibit transmurally-evoked (1 ms pulses, 10 Hz, 8-10 s trains) contractions of the longitudinal and circular muscles and the affinities of antagonists. Post synaptic α-adrenoceptors were identified by screening agonists and antagonists in carbachol-contracted tissues. In the circular muscle the order of potencies for inhibiting transmurally-induced contraction was: clonidine ≥ oxymetazoline ≥ UK 14,304 ≥ guanfacine > talipexole > phenylephrine > azepexole. The potency ratios relative to clonidine correlated to those previously derived using the rat ileum peristaltic reflex preparation. Most of the α-adrenoceptor agonists, however, caused only small inhibitions of the longitudinal muscle contraction in response to transmural stimulation, except phenylephrine and azepexole. RX 821002, yohimbine, rauwolscine, BRL 44408, phentolamine, idazoxan, ARC 239, and prazosin inhibited the effect of clonidine on the circular muscle response with apparent pK_B values best correlated with pK_B or pK_i values derived from the rat ileum peristaltic reflex preparation and other tissues known to have the α_2D-subtype. The rank order of potencies at inhibiting carbachol-induced responses of both muscle layers was: phenylephrine ≥ oxymetazoline > clonidine ≥ talipexole > azepexole >> guanfacine. UK 14,304 was inactive up to 10 μM. The EC₅₀ value of each agonist on the longitudinal muscle was not significantly different to the corresponding value on the circular muscle. Prazosin was more potent than yohimbine at inhibiting the relaxant effect of phenylephrine in both muscle layers of carbachol-contracted tissues. It is concluded that the recently identified α_2D-adrenoceptors of the rat ileum are located on cholinergic neurons controlling circular muscle contraction. The study also demonstrated the presence of postsynaptic α₁-adrenoceptors involved in mediating relaxation in both muscle layers. Received: 4 November 1996 / Accepted: 10 April 1997     

A Correlation Between the Permeability Characteristics of a Series of Peptides Using an in Vitro Cell Culture Model (Caco-2) and Those Using an in Situ Perfused Rat Ileum Model of the Intestinal Mucosa

In an attempt to establish an in vitro/in situ correlation of intestinal permeability data, the permeability coefficients (P _app) for a series of model peptides, which were determined using an in situ perfused rat ileum model, were compared to the permeability coefficients (P _mono) determined using an in vitro cell culture model (Caco-2). The model peptides, which were all blocked on the N-terminal (acetyl, Ac) and the C-terminal (amide, NH2) ends, consisted of D-phenylalanine (F) residues (e.g., AcFNH₂, AcFFNH₂, AcFFFNH₂). To alter the degree of hydrogen bonding potential, the nitrogens of the amide bonds were sequentially methylated [e.g., AcFF(Me)FNH₂, AcF(Me)F(Me)FNH₂, Ac(Me)F(Me)F(Me)FNH₂, Ac-(Me)F(Me)F(Me)FNH(Me)]. These peptides were shown not to be metabolized in the in situ perfused rat ileum system. The results of the transport experiments showed that there were poor correlations between the apparent permeability coefficients (P _app) determined in an in situ perfused rat ileum model and the octanol–water partition coefficients (r = 0.60) or the hydrogen bonding numbers (r = 0.63) of these peptides. However, good correlations were observed between the in situ P _app values for these peptides and their partition coefficients in heptane–ethylene glycol (r = 0.96) and the differences in their partition coefficients between octanol–water and isooctane–water (r = 0.86). These results suggest that lipophilicity may not be the major factor in determining the intestinal permeability of these peptides and that hydrogen bonding potential may be a major contributing factor. A good correlation (r = 0.94) was also observed between the P _app values determined for these peptides in the in situ perfused ileum model and those P _mono values determined in the in vitro cell culture model (Caco-2) (Conradi et al., Pharm. Res. 8:1453–1460, 1991). These results suggest that the permeability values determined in the Caco-2 cell culture model may be a good predictor of the intestinal permeability of peptides.     

Dependence and cross-dependence in the guinea-pig myenteric plexus

Summary Chronic activation of opioid receptors results in the development of tolerance and dependence. Tolerance may be confined to a single receptor type and thus has been termed selective tolerance. The present investigation reveals that prolonged activation of an inhibitory acting receptor type not only results in dependence associated with this receptor but also brings about cross-dependence. Cross-dependence involves both opioid receptors as well as non-opioid receptors, e. g. adrenoceptors. The experimental design employed did not permit conclusions to be drawn about whether those receptors exhibiting cross-dependence also developed tolerance. Regardless of the receptors and their specific subsequent transduction systems, all the receptors which showed dependence and cross-dependence proved sensitive to pertussis toxin, suggesting a critical function of GTP-binding proteins for the development of not only opioid dependence but also for drug dependence in general. Since multiple transmitter receptors may converge on the same ion channel, the concept of convergent dependences may be linked to GTP-binding proteins. However, no conclusions can be drawn with regard to the precise biochemical mechanisms underlying dependence. Send offprint requests to R. Schulz at the above address     

The sustained inward current in sino-atrial node cells of guinea-pig heart

 Single myocytes were dissociated from the sino-atrial (SA) node of guinea-pig hearts. Only a quite small fraction of the cell population showed spontaneous action potentials and these cells were characterized by the presence of the hyperpolarization-activated cation current I _f , the delayed rectifier K⁺ current I _K and the L-type Ca²⁺ current I _Ca,L as well as by the absence of both the transient outward current I _to and the inward rectifier K⁺ current I _K,1. After blocking I _f and I _K, depolarizing pulses from –80 mV revealed a large nicardipine-sensitive late current (NSLC). The NSLC was scarcely affected by decreasing extracellular [Ca²⁺] ([Ca²⁺]_o) from 1.8 to 0.1 mM, while it was decreased significantly by depleting [Na⁺]_o, differently from I _Ca,L. NSLC was blocked by nicardipine and was increased by Bay K 8644. NSLC was increased by isoprenaline and the additional application of acetylcholine reversed the increase of this current. We conclude that NSLC is largely composed of I _st described in the rabbit SA node pacemaker cells, and that I _st is unique for the pacemaker cells in mammalian SA node cells. Most of the quiescent cells showed neither I _f nor I _st. Received: 22 July 1996 / Received after revision: 30 September 1996 / Accepted: 9 October 1996     

EXTEROCEPTIVE STIMULATION AS A CONTINGENT FACTOR IN THE INDUCTION AND ELICITATION OF DELAYED TYPE HYPERSENSITIVITY REACTIONS TO 1 CHLORO-, 2-4, DINITROBENZENE IN GUINEA PIGS

This study attempted to determine whether a prior period of “stress” would elicit the sensitization reaction of the skin to topically applied chemical agents. A subthreshold concentration of 1-chloro-, 2-4, dinitrobenzene (DNCB) was applied to the skin of 40 guinea-pigs, 20 of which had been subjected to repetitive electrical shocks throughout the previous 15 minutes. They were examined 24 hours later, and were retested with DNCB at another site after 9 days for signs of delayed sensitization. The stressed animals exhibited a more severe contact-reaction (p <. 01) after the induction test and also after the delayed test.