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BACKGROUND: Interleukin (IL) 6 has an important role in the regulation of acute-phase proteins (APPs) during an acute-phase response. We studied IL-6 and other cytokines to determine if they regulate serum APP levels in the same way under the condition of the aberrant, long-lasting 'acute-phase response' that occurs in patients with chronic inflammation and cancer. METHODS: Serum levels of nine positive APPs [CRP, SAA, C1-INH, Bf, C5, C8, C9, alpha 1-acidic glycoprotein (AGP) and haptoglobin] and two negative APPs [transferrin and alpha 2-HS glycoprotein (AHSG)] were measured using immunochemical methods in 59 multiple myeloma patients and in 72 healthy control subjects. Serum IL-6 and tumour necrosis factor (TNF) alpha levels were determined by bioassays. RESULTS: IL-6 was negatively correlated with five out of nine (C1-INH, C8, C9, AGP and haptoglobin) positive APPs but positively correlated with C-reactive protein (CRP). When patients with high and low IL-6 serum concentration were compared, CRP levels were higher, AGP and haptoglobin levels were lower in the high- than in the low-L-6 group, whereas no significant difference between the two groups was found in levels of the other positive and negative APPs. TNF-alpha levels were negatively correlated with transferrin and AHSG levels. No difference in the levels of positive APPs was observed between patients with low and high TNF-alpha serum concentration. By contrast, levels of both transferrin and AHSG were significantly lower in the high- than in the low-TNF-alpha group. CONCLUSIONS: These findings indicate that, except for regulation of the negative APPs by TNF-alpha, the mechanism of APP regulation is different under the conditions of the short-term and the chronic, long-lasting 'acute-phase reaction'.

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The modulation of noradrenaline (NA) release from rat spinal cord slices was investigated and the subtype of presynaptic alpha 2-adrenoceptors involved in the negative feedback modulation was characterized using in vitro perfusion experiments. Rat spinal cord slices were loaded with [3H]NA and the release of radioactivity at rest and in response to field stimulation was determined. The alpha 2-adrenoceptor agonists, clonidine and dexmedetomidine inhibited the stimulation-evoked release of NA from spinal cord slices, whereas alpha 2-adrenoceptor antagonists yohimbine and CH-38083 (7,8-(methylenedioxy)-14-alpha-hydroxyalloberbane HCI), enhanced it. ARC 239, a selective alpha 2B-antagonist, had no effect on the release. In contrast, BRL 44408 a selective alpha 2A-antagonist increased the release of NA. Our results indicate that the negative feedback modulation of NA release from noradrenergic fibres in the spinal cord is mediated via alpha 2A subtype of alpha 2-adrenoceptors.

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The authors while describing their patients suffering from osteopetrosis disease, discuss its morphological aspects and possible patho-mechanism. The disease with osteosclerosis can be inherited recessively or dominantly. The recessively inherited type is less frequent and leads to early death due to secondary developing myelofibrosis. The dominantly inherited form is more benevolent, the patients are free of symptoms in half of cases. The patients described by the authors belong to the dominantly inherited type of the Albers-Schönberg disease. One of their patients suffers from rheumatoid arthritis and myelodisplastic syndrome apart from osteopetrosis. Having considered the publications authors have found data based on which the common source and connection of these three diseases can be rendered possible. Analyzing these data they draw attention to the possible pathogenic role of cytokines, first of all of the macrophag colony stimulating factor, moreover to the rheumatic manifestation of the paraneoplastic syndrome.

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The effects of alpha 2-adrenoceptor agonists (dexmedetomidine, oxymetazoline), alone or in combination with various alpha-adrenoceptor subtype-selective antagonists (CH-38083, idazoxan, WB4101, BRL44408, ARC-239, prazosin), on noradrenaline- and isoprenaline-induced lipolysis were investigated in human isolated abdominal subcutaneous fat cells. The rank order of potency of antagonists in preventing dexmedetomidine- and oxymetazoline-evoked suppression of isoprenaline-induced lipolysis was (pA2-values): CH-38083 (7.69 and 7.48) congruent to idazoxan (7.5 and 7.41) > BRL44408 (7.23 and 7.19) congruent to WB4101 (7.13 and 7.12) > prazosin (5.18 and 5.17) > ARC-239 (4.72, 4.9). While CH-38083 and idazoxan, non-subtype selective alpha 2-adrenoceptor antagonists and BRL44408, a selective alpha 2A-adrenoceptor antagonist as well as WB4101 potentiated the lipolytic effect of noradrenaline, ARC-239, the selective alpha 2B-adrenoceptor antagonist failed to affect it. In addition since the alpha 2A-adrenoceptor selective agonist, oxymetazoline concentration dependently inhibited the lipolytic effect of isoprenaline, and WB4101 and BRL44408 (alpha 2A-adrenoceptor antagonists) antagonised the effect of oxymetazoline in a competitive manner, it is concluded that the alpha 2A-adrenoceptor subtype is involved in antilipolysis. In addition, functional evidence was obtained that there is an interaction between alpha 2A- and beta-adrenoceptors located on the cell surface of adipocytes, through which locally released noradrenaline and/or circulating circulating adrenaline influence lipolysis.

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The effects of a series of alpha-2 adrenoceptor agonists and antagonists were examined on the stimulation-evoked release of tritium from a myenteric plexus-longitudinal muscle preparation of guinea pig ileum preincubated with [3H]choline or [3H]noradrenaline. Oxymetazoline, xylazine, detomidine and alpha-methylnoradrenaline caused a significant and concentration-dependent inhibition of the stimulation-evoked release of [3H]acetylcholine, with calculated IC50 values of 1.22 microM, 0.88 microM, 0.93 microM and 0.83 microM, respectively. Idazoxan (1 microM), CH 38083 (1 microM), WB 4101 (1 microM), prazosin (1-10 microM) and ARC 239 (1-10 microM) did not significantly affect the evoked release of [3H]acetylcholine. However, idazoxan, CH 38083 and WB 4101 antagonized the inhibitory effect of all agonists tested on [3H]acetylcholine release with calculated KB values in the nanomolar range, whereas prazosin and ARC 239 were ineffective. After incubation of ileum strips with [3H]noradrenaline, the stimulation-evoked release of tritium was significantly inhibited by oxymetazoline (0.1-1000 microM), xylazine (0.1-100 microM), detomidine (0.1-100 microM) or alpha-methyl-noradrenaline (0.1-100 microM), whereas it was enhanced by idazoxan (0.1-100 microM), CH 38083 (0.1-100 microM), WB 4101 (0.1-100 microM), prazosin (0.1 microM) and ARC 239 (0.1-100 microM). The order of potency found for these drugs in affecting the evoked release of [3H]noradrenaline was: xylazine > or = detomidine > alpha-methyl-noradrenaline >> oxymetazoline for agonists and ARC 239 > or = idazoxan > CH 38083 > WB 4101 for antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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The effects of alpha 2-adrenoceptor ligands on electrically stimulated [3H]acetylcholine release from longitudinal muscle strips of guinea-pig ileum were examined. Xylazine or oxymetazoline reduced the release of [3H]acetylcholine in a concentration-dependent manner, both these actions being antagonized by idazoxan, CH 38083, or WB 4101. Prazosin, considered as an alpha 2B-adrenoceptor antagonist, failed to modify the inhibitory effects of xylazine or oxymetazoline. It is concluded that the alpha 2-adrenoceptors involved in the modulation of acetylcholine release from cholinergic axon terminals of guinea-pig ileum are of the alpha 2A subtype.

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A group of 25 patients with non-Hodgkin's lymphoma was investigated. Patients diagnosed earlier were reclassified according to the Kiel system. A correlation between age distribution and histological malignancy was found. The time between the onset of symptoms and diagnosis was 1 year on an average. The majority of the patients belonged to stage IV. The survival rate was higher in the low-grade malignancy group than in the high-grade group. When assessing the prognosis, the histological classification as well as the clinical staging ought to be considered. The bone marrow was the most frequent extranodal site of involvement in stage IV. Cytopenic changes were almost invariably accompanied by bone marrow infiltration. All the 7 cases analysed for lymphocyte surface markers proved to be B cell type. No significant difference was seen between the results of single agent and combined chemotherapy.

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Renal function was tested after decreasing the plasma ionized calcium level of renal artery. During EDTA infusion, renal blood flow (RBFdir) increased, while CPAH, Ccreat, EPAH and Ecreat decreased. In the left kidney, urinary and sodium excretion did not change significantly, while calcium excretion reached a fifteen-fold higher value than the control one. The unchanged urinary and sodium excretion in spite of the decreased glomerular filtration rate may have been due to the osmotic diuretic effect of the Ca-EDTA complex. The decrease of CPAH and EPAH was probably the consequence of a change in the secretory capacity in the absence of Ca++. the vasodilatation occurring in the efferent arterioles during EDTA infusion would serve to explain the decrease in the glomerular filtration rate. It is concluded that humoral vasoactive factors, mainly angiotensin, may have an important role in the regulation of the diameter of the efferent arterioles and in this way in the regulation of glomerular function.

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