Interleukin-6-type cytokines in vivo: regulated bioavailability

Investigators have traditionally thought of the class of inflammation- and injury-associated cytokines in large part as "free" entities in the peripheral circulation. In the case of interleukin-6 (IL-6), the cytokine can be found in blood in complexes of molecular mass 400-500, 150-200, and 25-35 kDa in association with binding proteins that can include soluble IL-6 receptor (sIL-6R), anti-IL-6, and anti-sIL-6R IgG, and others. Sustained high levels of different particular IL-6 complexes are observed in the human circulation in cancer patients subjected to particular active anticancer immunotherapy regimens. In the "chaperoned" state, circulating IL-6 complexes display differential immunoreactivity in different ELISAs and possess differential biological activity as assayed ex vivo. The discovery of "chaperoned" circulating IL-6 in humans points to a new level of modulation of cytokine function, that of regulated bioavailability of IL-6 in vivo.     

Pasteurella multocida toxin is a mitogen for bone cells in primary culture

The effect of recombinant Pasteurella multocida toxin (PMT) on primary cultures of embryonic chick bone-derived osteoblastic cells was investigated. It was found that PMT was a potent mitogen for primary derived chicken osteoblasts. The toxin stimulated DNA synthesis and cell proliferation in quiescent osteoblasts at the first passage and accelerated cell growth in subconfluent cultures. Cell viability was not affected by PMT, even at relatively high concentrations. Osteoblast numbers increased in a dose-dependent manner in response to PMT. Intracellular inositol phosphates were elevated in response to PMT, but no elevation in cyclic AMP (cAMP) levels was evident. Indeed, PMT inhibited cAMP elevation in osteoblasts in response to cholera toxin at a stage before other PMT-mediated events take place. In addition to increased cell turnover, PMT down-regulated the expression of several markers of osteoblast differentiation. Both alkaline phosphatase and type I collagen were reduced, but osteonectin was not affected. The in vitro deposition of mineral in cultures of primary osteoblasts and osteoblast-like osteosarcoma cells was also inhibited by the presence of PMT. This suggests that PMT interferes with differentiation at a preosteoblastic stage.     

Centrally infused galanin-(1-15) but not galanin-(1-29) reduces the baroreceptor reflex sensitivity in the rat

It has been demonstrated previously that central administration of the N-terminal galanin fragment (1-15) elicits hypertension and tachycardia and antagonizes the hypotensive effect of the parent molecule galanin-(1-29). In order to further clarify the role of galanin in central cardiovascular control, the possible modulation of the baroreceptor reflex by both galanin molecules has been studied. Different groups of rats were injected in the lateral ventricle with subthreshold doses of galanin-(1-15) (0.1 nmol/rat, or 0.3 nmol/rat), with subthreshold doses of galanin-(1-29) (0.1 nmol/rat, and 0.3 nmol/rat) or with an effective dose of galanin-(1-29) (3.0 nmol/rat). The baroreceptor reflex was elicited by intravenous injections of different doses of L-phenylephrine before and after the intraventricular administration of galanin peptides. The changes of the bradycardic responses after galanin peptide injections as well as the modifications of the baroreceptor reflex sensitivity were evaluated. Intraventricular injections of galanin-(1-15) significantly inhibited the reflex bradycardia elicited by intravenous L-phenylephrine and thus decreased the baroreceptor sensitivity. However, neither subthreshold doses of galanin-(1-29) nor its effective dose were able to modulate these cardiovascular responses. From these data it may be suggested that the galanin fragment (1-15) plays a more important role in central cardiovascular regulation than galanin-(1-29), possibly acting on a specific receptor subtype which exclusively recognizes N-terminal fragments of galanin, and exists on cardiovascular areas of the central nervous system.     

Helicobacter pylori in children

Helicobacter pylori is the major cause of antral gastritis in children, however, it is not always associated with symptoms. The exception to this occurs in duodenal ulcer disease with which H. pylori is linked in children albeit less strongly than in adults. Duodenal ulcers do not recur in older children following eradication of H. pylori. The importance of asymptomatic carriage of H. pylori in children, particularly in relation to the duration of this infection and the subsequent development of gastric cancer, remain to be established. Helicobacter pylori is associated with both hypochlorhydria and persistent diarrhoea in children in developing countries, but the significance of this association is still unknown. Although there is no consensus on the optimal regimen for treating H. pylori infection in children, dual therapy with amoxycillin and bismuth subcitrate for 2 weeks followed by monotherapy with bismuth subcitrate for a further 6 weeks will eradicate H. pylori infection in the majority of children. Those who relapse may be treated with a repeat course plus metronidazole for 4 weeks. Compliance with such regimens is a problem and shorter treatment courses that are equally effective in children need to be defined. Similarly, studies are required on the influence of the intrafamilial reservoir of H. pylori infection on relapse after treatment and the need for whole family eradication therapy.     

Adverse effects of calcium binding contrast agents in diagnostic cardiac angiography. A comparison between formulations with and without calcium binding additives

RATIONALE AND OBJECTIVES: The authors compared complications and hemodynamic and electrophysiologic effects of two formulations of diatrizoate, one with additives that bind calcium and one without, in diagnostic cardiac angiography. METHODS: Two hundred twenty-three consecutive low-risk patients alternately received Hypaque 76 (group 1, little calcium binding effect), and MD 76 (group 2, significant calcium binding). Electrocardiographic and hemodynamic changes related to coronary angiography and left ventriculography were measured, and complications requiring treatment were recorded. RESULTS: There were more complications in patients in group 2 than in group 1 (18 versus 8, P = 0.04). Arterial pressure fell more, the QT interval increased more, and the heart rate fell more in group 2 after coronary angiography. CONCLUSIONS: Formulations of diatrizoate that minimize calcium binding are advocated for cardiac angiography when using high osmolality contrast media. The more detrimental effects that calcium binding has on myocardial function and cardiac conduction may lead to the higher incidence of complications.     

The apparent diffusion coefficient of water in gray and white matter of the infant brain

PURPOSE: The purpose was to obtain normal values of the apparent diffusion coefficient (ADC) in the infant brain and to compare ADC maps with T1- and T2-weighted images. METHOD: Diffusion was measured in nine infants with an ECG-gated SE sequence compensated for first-order motion. One axial slice at the basal ganglia level was investigated with the diffusion-encoding gradients in the slice-selection direction. RESULTS: On ADC maps, the corpus callosum and the optic radiations appeared dark before the onset of myelination, and the crus posterior of the internal capsule could be visualized before it appeared on T1- or T2-weighted images. In gray and white matter, the mean ADC ranged from 0.95 x 10(-9) to 1.76 x 10(-9) m2/s. In the frontal and occipital white matter, in the genu corporis callosi, and in the lentiform nucleus, the ADC decreased with increasing age. The cortex/white matter ratio of the ADC increased with age and approached 1 at the age of 30 weeks. CONCLUSION: ADC maps add information to the T1 and T2 images about the size and course of unmyelinated as well as myelinated tracts in the immature brain.     

Comparing functional results one year and ten years after ileal pouch-anal anastomosis for chronic ulcerative colitis

Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for most patients with chronic ulcerative colitis. Long-term results, however remain undefined; the major concern is that function may deteriorate. PURPOSE: The aim of this study was to assess functional outcome in a subgroup of patients who have an IPAA for chronic ulcerative colitis for > 10 years. METHODS: Among 1400 IPAA patients, 75 consecutive subjects (31 females and 44 males; median age 31 at operation) were identified who had the procedure prior to 1982. All patients had functional results recorded 1 year and 10 years following ileostomy closure. RESULTS: There were four deaths during the follow-up period; none were pouch related. Two patients refused ileostomy closure. Of the remaining 69 patients, there were 8 (11 percent) failures, leaving 61 subjects available for study. Stool frequency (7 +/- 3, mean +/- SD) remained unchanged. Of the 50 subjects with initially excellent daytime continence, 39 (78 percent) remained the same, 10 (20 percent) developed minor incontinence, and 1 developed poor control after 10 years. Four of 10 subjects (40 percent) with initial minor daytime incontinence remained unchanged, 4 (40 percent) improved, and 2 (20 percent) worsened. The one subject with poor control at one year was unchanged. Nocturnal fecal spotting increased over the 10-year period but not significantly (38 percent vs. 52 percent; P = 0.08). CONCLUSIONS: After IPAA, functional results in terms of stool frequency and rate of fecal incontinence did not deteriorate with time.