Effects of lumbar skin warming on gastric motility and blood pressure in humans

We examined the possibility that lumbar skin warming can increase gastrointestinal motility by investigating the electrogastrogram (EGG), blood pressure, and heart rate with psychometric ratings in healthy humans. Scores of mood state profiles showed that lumbar skin warming (42 degrees C, 20 min) decreased tension-anxiety, depression, anger-hostility, fatigue, and confusion of the participants. A multiple bandpass filter analysis of EGGs showed that a postural transition from orthostatic to supine for measurement caused an increase in dominant frequency of 25-29% towards the frequencies of the normal interdigestive migrating motor complex (IMC). The spectral power of the IMC band, 2.55-3.05 cycles/min, was increased by 20 min-warming, reflecting the increase in gastric contractility. No increase in the spectral power was observed in the time-matched control group without skin warming. Therefore, an increase in contractility is a characteristic of lumbar skin warming. The systolic blood pressure increased by 15% during warm stimulation. Interbeat intervals were not influenced by warm stimulation. An analysis of interbeat intervals by a fast Fourier transform method showed that the cardiac sympathetic and parasympathetic nerves did not play a major role in raising the blood pressure. Vasoconstriction of the mesenteric artery was therefore considered to cause a blood pressure increase during warming. It is hypothesized that vasoconstriction of the visceral arteries by lumbar skin warming increases the blood pressure and gastrointestinal contractility.     

Changes in blood pressure and muscle sympathetic nerve activity during water drinking in humans

To investigate the possible involvement of the sympathetic nervous system in pressor response during water drinking, muscle sympathetic nerve activity (MSNA), blood pressure (BP), and heart rate (HR) were continuously measured in healthy young volunteers throughout the experiments of a 5-min control, 2 min of drinking 500 ml water, and a 28-min recovery. To avoid the effects of water passing through the oropharyngeal and esophageal regions and/or effects of swallowing, an equal amount of water was directly infused to the stomach through a stomach tube for 2 min. Water drinking caused a transient increase in mean arterial pressure (MAP) and HR immediately after drinking (DeltaMAP, 12.6 +/- 2.1 mmHg; DeltaHR, +19.9 +/- 1.7 beats/min at the peak). An abrupt decrease of MSNA was observed directly during water drinking (Deltaburst rate, -6.9 +/- 1.3 bursts/min; Deltatotal activity, -2,606 +/- 491 U/min), and it increased to the baseline level thereafter. Gastric infusion had little or no effect on MAP, HR, and MSNA. The present study demonstrated that a pressor response during water drinking was associated with the attenuation of MSNA and not generated by gastric infusion of water at the same rate as in this drinking manner. In conclusion, the rapid rise in BP might be caused through stimulations from the oropharyngeal region, swallowing-induced factors, and/or a feedforward mechanism by a central descending signal from the higher brain centers.     

Spontaneous arterial baroreflex control of the heart rate during head-down tilt in heat-stressed humans

The purpose of this study was to elucidate the effect of raised body temperature per se during acute heat stress on the spontaneous arterial baroreflex control of heart rate (f _c) in humans. To investigate whether unloading of cardiopulmonary baroreceptors during whole-body heating would alter the arterial baroreflex control of f _c, we controlled loading of the cardiopulmonary baroreceptors by head-down tilt (HDT) at angles of 5°, 10°, 15°, and 30° during heat stress produced by hot-water-perfused suits. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and f _c. As an index of cardiopulmonary baroreceptor loading, the left atrial diameter (LAD) was measured by echocardiography. During whole-body heating, the LAD decreased with the rising body core temperature and increased with the HDT. The decreased LAD during heating almost recovered to the normothermic control level by 10° HDT. In the supine position, cardiac baroreflex sensitivity remained unchanged during heating. Arterial pressure, f _c and cardiac baroreflex sensitivity were not changed by HDT ranging from 5° to 30° during heating. These results suggest that cardiac baroreflex sensitivity remain unchanged during graded loading of the cardiopulmonary baroreceptors in heat-stressed humans. Also, we conclude that the sensitivity of the spontaneous arterial baroreflex controlling the f _c is not influenced by raised body temperature per se during acute heat stress. Electronic Publication     

Long-term outcomes using vascular grafts sealed with fragmented autologous adipose tissue for aortoiliac occlusive disease

The aim of this study was to test the safety and efficacy of fragmented autologous adipose tissue (FAT) grafts for revascularization in aortoiliac occlusive disease. Twenty-seven patients with atherosclerotic aortoiliac occlusive disease underwent surgical treatment using FAT grafts. A piece of adipose connective tissue was obtained from the operative wound, cut into small pieces, and pressed into the wall of a fabric vascular prosthesis. Cumulative primary patency rates were 92% at 1 year, 92% at 3 years, and 86% at 6 years. Cumulative secondary patency rates were 96%, 96%, and 90% for the same intervals. In this clinical study, the FAT grafts demonstrated good long-term patency rates and no particular problems. This is the first clinical report of long-term outcomes using FAT grafts for aortofemoral or aortoiliac bypasses. FAT grafts are thus safe for revascularization in aortoiliac occlusive disease.     

Isolation and phenogenetics of a novel circadian rhythm mutant in zebrafish

Widespread use of zebrafish (Danio rerio) in genetic analysis of embryonic development has led to rapid advances in the technology required to generate, map and clone mutated genes. To identify genes involved in the generation and regulation of vertebrate circadian rhythmicity, we screened for dominant mutations that affect the circadian periodicity of larval zebrafish locomotor behavior. In a screen of 6,500 genomes, we recovered 8 homozygous viable, semi-dominant mutants, and describe one of them here. The circadian period of the lager and lime (lag(dg2)) mutant is shortened by 0.7 h in heterozygotes,and 1.3 h in homozygotes. This mutation also shortens the period of the melatonin production rhythm measured from cultured pineal glands, indicating that the mutant gene product affects circadian rhythmicity at the tissue level, as well as at the behavioral level. This mutation also alters the sensitivity of pineal circadian period to temperature, but does not affect phase shifting responses to light. Linkage mapping with microsatellite markers indicates that the lag mutation is on chromosome 7. A zebrafish homolog of period1(per1) is the only known clock gene homolog that maps near the lag locus. However, all sequence variants found in per1 cDNA from lag(dg2) mutants are also present in wild type lines, and we were unable to detect any defect in per1 mRNA splicing, so this mutation may identify a novel clock gene.     

TNF microsatellite alleles a2 and b3 are not primarily associated with celiac disease in the Finnish population

Abstract: Recently, an independent association between tumor necrosis factor (TNF) gene polymorphism and ceiiac disease was observed in the Irish population. We tested this association in Finnish patients with celiac disease. The TNF microsatellite alleles a2 and b3 were strongly associated (P_corr<0.0001 for both) with celiac disease when the patients were compared to the random population. However, when the comparison was made with the DQ2-matched controls, no association could be found. We therefore conclude that in Finland the TNFa2 and b3 alleles are associated with DQ2-positive haplotypes rather than celiac disease.     

Genetic susceptibility to gluten sensitive enteropathy in Irish setter dogs is not linked to the major histocompatibility complex

Abstract: Gluten sensitive enteropathy (GSE) in Irish setter dogs has been proposed as an animal model for human celiac disease (CD), in which the major histocompatibility complex (MHC) class II alleles HLA DQAl*0501 and DQBl*0201 play an important role. To investigate whether an orthologous MHC class II region is involved in canine GSE, we undertook a linkage study in two large families of gluten sensitive Irish setter dogs. A total of 44 dogs in these pedigrees were genotyped for DQA1, DQB1 and C.2202 alleles, along with 30 unrelated healthy Irish setters. No genetic linkage between the DQ or C.2002 loci and GSE was detected. In contrast to CD, susceptibility to canine GSE does not appear to be determined by variation within the MHC class II gene cluster. Therefore, canine GSE may not be an appropriate model for CD, but nevertheless remains an important disease for advancing knowledge of pathological processes in the intestine.     

Inhibitory effect of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazolo [3,4-d] pyrimidine-2-carboxylate (AA-2379) on type III allergic (Arthus) reaction

Methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazolo[3,4-d]pyrimidine-2-carboxylate (AA-2379), a non-steroidal, non-acidic agent, markedly inhibits type III allergic (Arthus) reaction; the ID₅₀ values of AA-2379 in the rat reversed passive Arthus pleurisy, the rat active Arthus pleurisy, and the reversed passive Arthus reaction in rat skin were 5–10 mg/kg, p.o., and 30 mg/kg of AA-2379 inhibited the active Arthus reaction in rabbit skin by about 50%. Dexamethasone, but not acidic non-steroidal anti-inflammatory drugs and aminopyrine, inhibited the Arthus reaction. The vascular permeability in the reversed passive Arthus pleurisy is enhanced biphasically in the early response mediated by physiologically active amines, prostaglandins, and leukotrienes, and in the late response mediated by complements and polymorphonuclear leukocytes (PMNs). AA-2379 inhibited the late response more potently than the early one. Furthermore, when given after the early response was reduced, AA-2379 obviously inhibited the late response. Rat zymosan-induced paw edema and mouse zymosan-activated serum-induced peritonitis, mediated by complements, were dose-dependently inhibited by AA-2379; the ID⁵⁰ values were 11.4 and 10.2 mg/kg, p.o., respectively. The results suggest that AA-2379 differes from non-steroidal anti-inflammatory agents in strongly inhibiting the late response of the Arthus reaction, which associated with PMNs.