Jerzy Jochem

Influence of intravenously administered leptin on nitric oxide production, renal hemodynamics and renal function in the rat.

We investigated the effect of leptin on systemic nitric oxide (NO) production, arterial pressure, renal hemodynamics and renal excretory function in the rat. Leptin (1 mg/kg) was injected intravenously and mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF) and renal cortical blood flow (RCBF), were measured for 210 min after injection. Urine was collected for seven consecutive 30-min periods and blood samples were withdrawn at 15, 45, 75, 105, 135, 165 and 195 min after leptin administration. Leptin had no effect on MAP, HR, RBF, RCBF and creatinine clearance, but increased urine output by 37.8% (0-30 min), 32.4% (31-60 min) and 27.0% (61-90 min), as well as urinary sodium excretion by 175.8% (0-30 min), 136.4% (31-60 min) and 124.2% (61-90 min). In contrast, leptin had no effect on potassium and phosphate excretion. Plasma concentration of NO metabolites, nitrites + nitrates (NOx), increased following leptin injection at 15, 45, 75 and 105 min by 27.7%, 178.1%, 156.4% and 58.7%, respectively. Leptin increased urinary NOx excretion by 241.6% (0-30 min), 552.6% (31-60 min), 430.7% (61-90 min) and 88.9% (91-120 min). This was accompanied by increase in plasma and urinary cyclic GMP. These data indicate that leptin stimulates systemic NO production but has no effect on arterial pressure and renal hemodynamics.

Histamine in food: is there anything to worry about?

Biogenic mono-, di- and poly-amines are widely distributed among living organisms. The amines fulfil many important functions in the human body both in the periphery and brain. Some authors suggest that foods rich in biogenic amines, especially histamine, present high health hazards for consumers. However, this is conditional on a range of other factors. The alimentary tract is well equipped with enzymes that inactivate amines and the blood-brain barrier prevents them entering the brain from the circulation. Oxidative deamination, methylation, acetylation and transglutamylation are the degradation pathways which operate efficiently in the stomach, intestines and liver. Particularly important is oxidative deamination. Food histamine poisoning or cheese reaction, manifested itself in patients treated with drugs that inhibit amine oxidases or in patients showing an enterocytic diamine oxidase deficit. It is rather food allergy, which should worry us more, as endogenous histamine release from mast cells is more dangerous. Preventive measures should be undertaken against increases in food allergies.

Involvement of arginine vasopressin in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats

AbstractObjective and design:Histamine is a potent stimulator of arginine vasopressin (AVP) release and therefore, the role of AVP was studied in the reversal of critical haemorrhagic hypotension induced by endogenous central histamine after inhibition of histamine N-methyltransferase (HNMT) activity in rats. Material:In 48 ethylurethane-anaesthetised male Wistar rats cardiovascular parameters and plasma hormone concentrations were measured. Treatment:Haemorrhage-shocked rats with mean arterial pressure (MAP) 20–25 mmHg were injected intracerebroventricularly (icv) with HNMT inhibitor metoprine (20 μg) after pre-treatment with V1a, V1b and V2 receptor antagonists – [β-mercapto-β,βcyclopentamethylenepropionyl1, O-me-Tyr2,Arg8]AVP (10 μg/kg; iv), SSR149415 (10 mg/kg; ip) and [adamantaneacetyl1,O-Et-D-Tyr2,Val4, aminobutyryl6,Arg8,9]AVP (10 μg/kg; iv), respectively, or saline. Methods:MAP, heart rate (HR) and regional haemodynamics were monitored within 2 h after treatment or to death if it occurred earlier. Plasma hormone concentrations were measured using enzyme immunoassays. ANOVA followed by Neuman-Keules test, and Fisher’s exact test were used to compare the results. Results:Metoprine produced a long-lasting increase in MAP, HR, renal, hindquarters and mesenteric blood flows, and a 100% survival at 2 h (P < 0.05 vs. the control group). The action was associated with increased plasma AVP concentration (587.5 ± 98.9 vs. 387.3 ± 125.2 pg/ml; P < 0.05) in comparison to the control group as measured at 20 min after treatment. V1a, but not V1b and V2, receptor antagonist inhibited metoprine-induced haemodynamic effects, with no influence on survival at 2 h. SSR149415 did not influence ACTH and adrenaline plasma concentrations in the metoprine-treated group. Conclusion:AVP, acting via V1a receptors, is involved in endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats.

Analysis of procalcitonin and CRP concentrations in serum of patients with chronic spontaneous urticaria

BackgroundOur previous findings showed the importance of analysing the peripheral markers of acute phase response (APR) activation, C-reactive protein (CRP) and IL-6 in the context of urticaria activity and severity. However, these biomarkers do not reliably differentiate between APR to infectious and the disease severity.AimIn order to investigate a possible association between the immune-inflammatory activation markers CRP and procalcitonin (PCT).MethodsSerum PCT and CRP concentrations were measured in patients with CU of varying severity as well as in healthy subjects.ResultsSerum PCT and CRP concentrations were significantly increased in more severe CU patients when compared to healthy controls and mild CU, and within the CU population there was a significant correlation between concentrations of PCT and CRP. Serum PCT concentrations remained within normal ranges in most CU patients and were only slightly elevated in some severe CU cases.ConclusionsPCT serum concentration may be only slightly elevated in some cases of severe CU. Upregulation of PCT synthesis accompanied by parallel changes in CRP concentration reflects a low-grade systemic inflammatory response in CU. PCT should be considered as a better marker than CRP to distinguish between APR to infection and an active non-specific urticarial inflammation.

Increased serum complement C3 and C4 concentrations and their relation to severity of chronic spontaneous urticaria and CRP concentration

Chronic spontaneous urticaria (CU) is associated with activation of the acute phase response (APR). Nevertheless, APR-associated proteins have not been well characterized as potential biomarkers of the disease severity. To assess the pattern of complement proteins C3 and C4 – the acute phase reactants in patients with CU. C3, C4 and CRP concentrations were measured in serum of 70 patients showing different degrees of urticarial severity as well as in 33 healthy subjects. Serum C3 and C4 concentrations were significantly increased in CU patients as compared with the healthy subjects and exceed the normal lab range by about 5% and 10%, respectively. Significant differences were found between patients with mild and increased CU severity. In addition, significant correlations were observed between C3, C4 and CRP concentrations. More severe CU is characterized by higher production of C3 and C4 complements accompanied by parallel changes in CRP concentration.

Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats.

To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity severalfold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum — reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.

Interactions between the histaminergic and angiotensinergic systems in the central cardiovascular regulation in rats

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Centrally injected histamine increases posterior hypothalamic acetylcholine release in hemorrhage-hypotensive rats.

Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

Increased plasma concentration of vascular endothelial growth factor in patients with atopic dermatitis and its relation to disease severity and platelet activation

BackgroundOverproduction of vascular endothelial growth factor (VEGF) in atopic dermatitis (AD) lesions has previously been observed. It is also known that platelet is an important source of VEGF and platelet factor 4 (PF-4), a potential marker of AD severity.AimTo evaluate concentrations of VEGF and its soluble receptors (sVEGF-R1 and sVEGF-R2) in the plasma of AD patients and to examine its possible correlation with disease severity and plasma concentrations of PF-4, a platelet activation marker.MethodsPlasma concentrations of VEGF and its receptors and levels of PF-4 were measured by an immunoenzymatic assay in 51 AD patients and in 35 healthy non-atopic controls. The severity of the disease was evaluated using the eczema area and severity index.ResultsAD patients showed significantly increased VEGF and PF-4 plasma concentrations as compared with the controls. Plasma concentrations of sVEGF-R1 and sVEGF-R2 did not differ between the groups. There were no remarkable correlations between plasma VEGF concentration and disease severity or between VEGF and PF-4 concentration.ConclusionsThis study shows that plasma concentration of VEGF may be increased in patients suffering from AD. It seems that plasma VEGF concentration is not a useful marker of disease severity and, apart from platelets, other cells might also release the cytokine.

Central serotonin-induced pressor effect in rats is mediated in part via the histaminergic system

1 Department of Basic Medical Sciences, Faculty of Public Health, Medical University of Silesia, Piekarska 18, 41-902 Bytom, Poland 2 Department of Physiology, Faculty of Medicine and Dentistry, Medical University of Silesia, H. Jordana 19, 41-808 Zabrze, Poland, Fax: ++48 32 2722362, e-mail: jjochem@poczta.onet.pl 3 Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia