Neuropeptides in idiopathic chronic constipation (slow transit constipation)

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.     

Therapeutic Consequences of Variation in Intraarterial Pressure Measurements After Iliac Angioplasty

Purpose: To assess the accuracy of intraarterial measurement of transstenotic pressure gradients for the detection of hemodynamically suboptimal iliac angioplasty. Methods: In 14 patients, referred for diagnostic angiography, mean pressure gradients in the aorta and iliac artery were obtained twice, using a double-sensor pressure catheter. Additional iliac measurements were performed during pharmacologically induced flow augmentation. Repeatability was assessed by calculation of the mean difference plus standard deviation (MD ± SD) and repeatability coefficient (2 × SD). These results were extrapolated to 137 iliac angioplasty procedures with secondary stenting where there was a residual pressure gradient > 10 mmHg. Results: MD ± SD for repeated measurements at rest and during flow augmentation were 0 ± 2 mmHg and 1 ± 3 mmHg, respectively. Repeatability coefficients were 3 and 6 mmHg. Mean pressure gradients after hemodynamically insufficient angioplasty were 8 ± 7 mmHg at rest and 17 ± 5 mmHg following vasodilatation. Inaccurate pressure recordings may have led to inappropriate stent placement in less than 2.5%, and inappropriate denial of stent placement in less than 5% of the lesions. Conclusion: Variability of intraarterial pressure measurements has little consequence in the detection of hemodynamically significant stenosis after angioplasty. Received: 0/00/00/Accepted: 0/00/00     

The Membrane Lipid Cholesterol Modulates Anesthetic Actions on a Human Brain Ion Channel

Background: Molecular theories of general anesthesia often are divided into two categories: (l) Anesthetics may bind specifically to proteins, such as ionic channels, and alter their function directly, and (2) anesthetics may alter the functions of integral membrane proteins indirectly through modification of the physical properties of the membrane. Recent studies have provided evidence that anesthetics can bind to proteins and modify their function directly, bringing into question the role of the membrane in anesthetic interactions. To reexamine the role of membrane lipids in anesthetic interactions, an experimental approach was used in which the membrane lipid composition could be systematically altered and the impact on anesthetic interactions with potential targets examined.

Methods: Sodium channels from human brain cortex were incorporated into planar lipid bilayers with increasing cholesterol content. The anesthetic suppression of these channels by pentobarbital was quantitatively examined by single channel measurements under voltage-clamp conditions.

Results: Changes in cholesterol content had no effect on measured channel properties in the absence of anesthetic. In the presence of pentobarbital, however, cholesterol inhibited anesthetic suppression of channel ionic currents, with 1.9% (weight/weight, corresponding to 3.5 mol%) cholesterol decreasing anesthetic suppression of sodium channels by half.     

X-Ray Study of the Cat Hindlimb During Treadmill Locomotion

With pulsed X-ray cinematography we have analysed the angular excursions of the distal hindlimb joints (proximal interphalangeal, PIP; metatarsophalangeal, MTP; ankle) in cats walking on a treadmill. These distal joints transmit the body weight and the dynamic forces onto the ground. We have included the knee and hip joints in the analysis to relate the angular excursions of the proximal and distal joints and to verify the data previously obtained with external markers on the kinematics of the proximal joints. At the beginning of the stance phase the PIP joints flexed rapidly, the MTP joints extended slowly and the ankle and knee yielded under body weight. Whereas the PIP joints maintained a rather constant angular position of −75° throughout the stance phase, extension continued in the MTP joints from −230° at touch-down to −270° at the end of the stance phase. Around 50 ms before lift-off the MTP joints flexed rapidly. Early (−30 ms) after lift-off this flexion changed into a slow extension. The PIP joints extended swiftly at the stance-swing transition and moderately at the end of the swing phase. During the middle part of the swing phase they flexed slowly. Small rotatory movements around the long axis of the foot took place in the last 100 ms of the swing phase. The results of this study on the distal joints are discussed in relation to the placing of the paw, to the translation of forward propulsion into a MTP movement and to the lifting of the paw (conventionally described as toe curling). They show a differentiated mechanical interaction between the different distal limb joints during these different phases, which must be known in detail to interpret the corresponding electromyographic data and to understand how the hip is moved forward over the MTP joints which serve as the final pivot during stance.