Andrzej Madej

Neuroleptics normalize increased release of interleukin-1β and tumor necrosis factor-α from monocytes in schizophrenia

Abstract Some recent reports show that schizophrenia is accompanied by changes in lymphocyte activity. This study investigated the activity of monocytes by determining their release of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Monocytes were immunomagnetically isolated from the peripheral blood of schizophrenic patients before and after neuroleptic medication and stimulated by lipopolisaccharide (LPS) in vitro. The monocytes of schizophrenic patients released significantly higher amounts of IL-1β and TNF-α than those of healthy controls. Treatment with the typical neuroleptics haloperidol and perazine decreased the release of IL-1β and TNF-α to the control levels. The study has shown that the activity of monocytes is increased in schizophrenia and that neuroleptic treatment normalizes this activity.

Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates.

Both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as well as peroxisome proliferator-activated receptor (PPAR)α activators (fibrates) proved to be effective in the primary and secondary prevention of cardiovascular diseases. The benefits of hypolipemic therapy in cardiovascular diseases cannot be explained only by the lipid-lowering potential of these agents. The aim of this study was to clarify the effect of hypolipemic agents on proinflammatory cytokine release from human monocytes in relationship with their action on plasma levels of sensitive systemic marker of low-grade vascular inflammation. Plasma lipid and high-sensitivity C-reactive protein (hsCRP) levels, and the release of tumor necrosis factor-α (TNFα) and interleukin-1β from monocytes were assessed at baseline and 30 and 90 days following randomization of IIa dyslipidemic patients into fluvastatin or simvastatin groups and randomization of type IIb dyslipidemic patients to the micronized form of either ciprofibrate or fenofibrate. Lipopolysaccharide-stimulated monocytes from dyslipidemic patients released significantly more TNFα (types IIa and IIb dyslipidemias) and interleukin-1β (type IIa dyslipidemia) in comparison with monocytes in 59 age-, sex-, and weight-matched control subjects. Their baseline hsCRP levels were also higher. Both statins and fibrates reduced the release of TNFα and interleukin-1β, and lowered plasma hsCRP levels. The effects of hypolipemic agents on cytokine release and plasma hsCRP were unrelated to their lipid-lowering action. Our results have demonstrated that type IIa and IIb dyslipidemic patients exhibit the abnormal pattern of TNFα and interleukin-1β production by activated monocytes. Both HMG-CoA reductase inhibitors and PPARα activators normalize monocytic secretion of these cytokines, and this action may partially contribute to the systemic antiinflammatory effect of hypolipemic agents. The statin- and fibrate-induced suppression of proinflammatory cytokine release from monocytes seems to play a role in their beneficial effect on the incidence of cardiovascular events.

Atorvastatin and fenofibric acid differentially affect the release of adipokines in the visceral and subcutaneous cultures of adipocytes that were obtained from patients with and without mixed dyslipidemia

In this study, we compared the effects of atorvastatin and fenofibric acid, which were administered alone or in combination, on the secretory function of human adipocytes that were obtained from the visceral and subcutaneous adipose tissues of 19 mixed dyslipidemic patients and 19 subjects with a normal lipid profile. The adipocytes were incubated in vitro in the presence of atorvastatin and/or fenofibric acid. The secretory function of the cells was determined using ELISA assays. The visceral adipocytes released significantly more adiponectin and IL-6 and less PAI-1 than those that were obtained from subcutaneous tissue. The levels and patterns of adipokine release differed between the patients with or without lipid abnormalities and between the adipocytes that were obtained from visceral or subcutaneous adipose tissue. The culture that contained hypolipidemic drugs resulted in the significant changes of the release of adipokines. The effects of atorvastatin and fenofibric acid on the hormonal function of human adipocytes may be, in part, responsible for the clinical efficacy of these drugs in the prevention and treatment of dyslipidemia-related cardiovascular and metabolic disorders. The study supports the concept that the pleiotropic effects of fenofibrate and atorvastatin may be, in part, a result of their impact on the secretory function of adipocytes.

Hypolipidemic drugs affect monocyte IL-1beta gene expression and release in patients with IIa and IIb dyslipidemia.

Because atherosclerosis has been proven to be an inflammatory disease, it became obvious that the proper treatment of dyslipidemic patients should not only correct lipid parameters but also inhibit the inflammatory state. One of the crucial proinflammatory and procoagulant cytokines participating in the pathogenesis of atherosclerosis is interleukin-1β (IL-1β). Therefore, the aim of the study was to asses the effect of statin and fibrate therapy (for dyslipidemia IIa and IIb, respectively) on IL-1β gene expression and monocyte release evaluated in each patient. Additionally, the effect of hypolipidemic therapy on fibrinolysis was evaluated. The study was carried out in 37 patients: 12 with biochemically confirmed type IIa dyslipidemia (treated with atorvastatin), 12 with type IIb dyslipidemia (treated with fenofibrate), and 13 age- and sex-matched normolipidemic persons (control). IL-1β concentrations in cultured monocytes and PAI-1 (Plasminogen Activator Inhibitor) plasma levels were measured using the ELISA method. To evaluate the expression of IL-1β gene in monocytes, a semiquantitive RT-PCR procedure was performed. The results were normalized with the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a housekeeping gene. Although IL-1β monocyte release was markedly elevated in patients with atherogenic dyslipidemias, IL-1β gene expression was only slightly and nonsignificantly higher in the studied groups versus control. We have observed significant reduction of IL-1β mRNA expression after 30-day treatment with the examined drugs (atorvastatin, 2.10 ± 0.50 versus 1.05 ± 0.15; P < 0.001, fenofibrate; 2.27 ± 0.48 versus 1.23 ± 0.27; P < 0.01). There was no significant difference between statin and fibrate effect on IL-1β mRNA expression. Similarly, we have noticed significant reduction of IL-1β release by cultured monocytes after 30-day statin therapy (133.0 ± 5.7 pg/mL versus 77.0 ± 3.6 pg/mL; P < 0.01) and fibrate therapy (143.9 ± 6.5 pg/mL versus 86.2 ± 5.9 pg/mL; P < 0.01). Besides this antiinflammatory effect, we have observed a 30% reduction of PAI-1 plasma levels in both treated groups. In conclusion, effective 1-month hypolipidemic therapy with atorvastatin or fenofibrate diminished plasma levels of proinflammatory and procoagulatory state markers.

In-vitro Immunomodulatory Effects of Haloperidol and Perazine in Schizophrenia

Summary: There are some reports describing concurrent changes in lymphocytic and monocytic activities in schizophrenia. In this study we investigated T cell activity in schizophrenic patients by measuring the release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) by T cells and the percentages of CD4+ and CD8+ cells in blood. The release of IL-2 and sIL-2R by T cells was evaluated in dilute whole blood after in-vitro stimulation with phytohemagglutinin. IL-2 levels and the percentage of CD4-cells tended to decrease and sIL-2R levels decreased significantly in schizophrenic patients. Haloperidol and perazine significantly decreased IL-2 levels and increased sIL-2R levels and the percentage CD4-cells. IL-2 and sIL-2R levels were lower in patients with a predominance of positive symptoms. The neuroleptic-induced increase in sIL-2R levels was higher in patients with a predominance of positive symptoms compared with those in whom both positive and negative symptoms were severe. The study has shown that T-cell activity is reduced in schizophrenia and that neuroleptics may have immunomodulatory properties.

Effects of bisoprolol and cilazapril on the central retinal artery blood flow in patients with essential hypertension—preliminary results

Abstract Background. A growing body of evidence suggests that effective blood pressure reduction may inhibit the progression of microvascular damage in patients with essential arterial hypertension. However, the potential influence of anti-hypertensive drugs on ocular circulation has not been studied sufficiently. Purpose. The aim of our study was to evaluate the effects of anti-hypertensive therapy on blood flow in the central retinal artery in patients with systemic arterial hypertension. Material and methods. Twenty patients with essential arterial hypertension, aged 32–46 years, were examined with Doppler ultrasonography (10 MHz ultrasound probe). Blood flow velocities, pulsatility, and vascular resistance were determined before and 3 hours after systemic application of either bisoprolol 5 mg or cilazapril 2.5 mg. Results. Administered bisoprolol significantly decreased maximum (9.8 ± 0.5 cm/s versus 8.5 ± 0.6 cm/s; P < 0.05) and minimum (2.75 ± 0.19 cm/s versus 1.75 ± 0.27 cm/s; P < 0.02) velocity, increased the Pourcellots index (0.71 to 0.79; P < 0.05) in central retinal artery. There were no statistically significant changes in central retinal artery blood flow after administration of cilazapril. Conclusion. Systemic application of beta-blockers may unfavourably disturb the ocular blood flow.

Innowacyjność różnych typów rolniczych gospodarstw w opinii rolników z makroregionu Mazowsza i Podlasia

abstrakt. Przedmiotem pracy są zagadnienia innowacyjności w rolnictwie w świetle opinii właścicieli różnych typów rolniczych gospodarstw (bydlęce, trzodowe, mieszane, roślinne), położonych w makroregionie Mazowsza i Podlasia. Celem badań było poznanie źródeł informacji o innowacjach w rolnictwie i zapotrzebowania gospodarstw na doradztwo rolnicze. Zastosowano celowy dobór próby badawczej, a opinie rolników uzyskano metodą ankietową. Postawy proinnowacyjne wykazywali w większości właściciele gospodarstw bydlęcych i roślinnych. Właściciele wszystkich typów gospodarstw najczęściej korzystali z informacji o nowościach w rolnictwie od doradców ODR i z czasopism fachowych, a także zdobywano je na kursach i szkoleniach oraz z internetu i telewizji. Gospodarstwa specjalizujące się w produkcji zwierzęcej (bydlęce, trzodowe) i roślinnej miały większe zapotrzebowanie na doradztwo rolnicze niż gospodarstwa z produkcją mieszaną. W zakresie doradztwa rolniczego największym zainteresowaniem cieszyły się porady świadczone przez ODR i agencje rolne.