The effect of aripiprazole on leptin levels of patients with chronic schizophrenia and a comparison of leptin, acute phase protein, and cytokine levels with regard to body mass and body composition indexes.

INTRODUCTION: The aim of this study was to test the effect of aripiprazole on leptin, insulin, acute phase proteins, and selected cytokines levels in patients with chronic schizophrenia. Additionally, levels of leptin, insulin, acute phase proteins, and cytokines were compared with body mass and body composition indexes. MATERIAL AND METHODS: Levels of leptin, insulin, serum amyloid A (SAA), tumour necrosis factor alpha (TNF-α), and interleukins 17A (IL-17A) and 18 (IL-18) in blood serum were measured for 17 patients before and after 28 days of administering aripiprazole by means of enzyme-linked immunosorbent assay (ELISA). Before and after the study, body mass and waist circumference (WC) were also measured, and body mass index (BMI) and body fat percentage (BF%) were estimated. The sex of each patient was taken into account. RESULTS: After administration of aripiprazole the reduction of levels of leptin, insulin, SAA, and TNF-a were statistically significant, similarly to body mass reduction and decrease in WC, BMI, and BF%, which were also statistically significant. A positive correlation between leptin and BF% and negative correlation between insulin and body mass and body composition indexes were observed before and after the study. High sensitivity C-reactive protein (hsCRP) and hsCRP/albumin positively correlated with BMI before the treatment. In the group of women a statistically significant positive correlation between TNF-α and IL-17A and body mass and body composition indexes was observed, and in the group of men a negative correlation between IL-18 and BMI, WC, and BF% was noted. CONCLUSIONS: The effect of aripiprazole is connected to its anti-inflammatory activity. A 28-day treatment resulted in reduction of adipose tissue, and in the group of women it returned their leptin sensitivity to normal levels. A change of psychotropic treatment and administration of aripiprazole reduces cardiometabolic risks.

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.

Distribution in Rats Internal Organs of Intraperitoneally Given 125I-Labeled Heptapeptide [2-8]-Leucopyrokinin ([2-8]-LPK), a Truncated Analog of Insect Neuropeptide Leucopyrokinin.

BACKGROUND: It was previously found that synthetic, insect-derived octapeptide leucopyrokinin (LPK) applied directly into the lateral brain ventricle induced a significant antinociceptive effect in rats. Its synthetic truncated analog heptapeptide [2-8]-leucopyrokinin displayed a stronger antinociceptive effect in comparison to native LPK. Moreover it was previously found a high accumulation of these both 125I-labeled peptides in adrenals, as well as in hypothalamus and in hippocampus of rats brain. OBJECTIVES: The aim of the present study was to assess the distribution of 125I-labeled [2-8]-leucopyrokinin in rats' internal organs an in several parts of the brain after peripheral - intraperitoneal (i.p.) administration. MATERIAL AND METHODS: The study was performed on male Wistar rats. A synthetic [2-8]-leucopyrokinin ([2-8]-LPK) was iodinated with Na125I. On the day of experiment a solution of 125I-[2-8]-LPK was i.p. injected and the next after 1 and 24 h animals were sacrificed by decapitation. Radioactivity levels in samples of parts of the brain and of internal organs were determined by counter Gamma Auto Count. RESULTS: A uniform, low accumulation 125I-[2-8]-LPK was found in evaluated samples of the brain and in internal organs. CONCLUSIONS: The results of the present study indicate a weak penetration into the brain and internal organs of intraperitoneally applied 125I-[2-8]-LPK in rats and correspond with previously determined weak biological effects of i.p. injected LPK and [2-8]-LPK.

Effect of alloferon 1 on central nervous system in rats.

Alloferon 1 is an insect-derived peptide with potent antimicrobial and antitumor activity. It was isolated from blood of an experimentally infected insect, the blow fly Callifora vicina. Synthetic alloferon 1 reveals a capacity to stimulate activity of NK cells and synthesis IFN in animal and human models. Moreover, it was demonstrated antiviral and antitumor activity of alloferon 1 in mice. There are no data on influence of alloferon 1 on central nervous system. The aim of present study was to determine an effect of alloferon 1 on rats' central nervous system by some behavioral tests: open field test, hole test, score of rats irritability, and determination of memory consolidation in the water maze test. Moreover, a probable antinociceptive effect of alloferon 1 in rats was determined by a tail immersion test and hot plate test. Experiments were performed on female Wistar rats. Seven days before experiments, rats were anesthetized with ketamine and xylazine and polyethylene cannulas were implanted into the right lateral brain ventricle (i.c.v.). On the day of experiment, alloferon 1 dissolved in a volume of 5 µL of saline was injected directly i.c.v. through implanted cannulas at doses of 5-100 nmol. It was found that alloferon 1 had slight effect on locomotor and exploratory activity, induced some decrease of rat irritability and a weak impairment of rats memory (only at the low dose of 5 nmol). On the other hand, the higher dose of this peptide exerts significant antinociceptive effect. Obtained results indicate that alloferon 1 do not exert any evidently toxic effect on central nervous system in rats. Therefore, alloferon 1 may be good new drug with antitumor and antinociceptive activity.

Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity.

BACKGROUND: Weight gain and metabolic abnormalities occur in chronic schizophrenia patients treated with atypical antipsychotics. The purpose of the study was to evaluate changes in serum levels of C-reactive protein (CRP), insulin and cytokines (IL-6, TNF-α, IL-1ß, IFN-γ, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-ß1, IL-4, and IL-10) after switching to aripiprazole. METHODS: Cytokine, hsCRP and insulin measurements were performed in patients (n=17) on day 0 and day 28 of the study using standard ELISA assays. The psychopathological status was assessed using PANSS. WC and BMI were measured and calculated, respectively. RESULTS: We observed high clinical efficacy in aripiprazole linked to a 2.7% weight loss. There were statistically significant reductions in PANSS scores and body parameters (p<0.001). After 28 days we detected a significant reduction in hsCRP (p<0.001), insulin (p<0.001), IL-1ß, IL-6, TNF-α, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-ß1, IL-4 (p<0.001), IFN-γ (p<0.05) and a significant elevation of IL-10 (p<0.001). There was a significant negative correlation between IL-10 levels and PANSS positive, negative and total scores after the study (p=0.022, p=0.003, p=0.008, respectively). CONCLUSIONS: Aripiprazole limits inflammatory processes by enhancing anti-inflammatory signaling. Aripiprazole also reduces the risk of metabolic abnormalities.

Three pregnancies in a Marfan syndrome patient after a mitral and tricuspid valve surgery.

Marfan syndrome is an autosomal dominant disorder of connective tissue with up to 25% of cases related to a spontaneous mutation. It has been associated with perinatal loss, preterm labor and, potentially a rupture of the maternal aortic arch. We present a case of a woman diagnosed with Marfan syndrome after a miscarriage of her first pregnancy. At the time of diagnosis she had mild aortic bulb dilation and insufficiency of the mitral and tricuspid valves. She underwent cardiosurgical correction, after which she had two uneventful pregnancies. This case suggests that preconceptional correction of valve defects in women with Marfan syndrome may decrease the risk of cardiac decompensation during future pregnancies. Additionally close clinical follow up and the appropriate use of beta-adrenergic blockade may decrease the risk of aortic rupture, a significant risk factor for mortality in pregnant women.

Neonatal DSP-4 treatment modifies antinociceptive effects of the CB1 receptor agonist methanandamide in adult rats.

To study the influence of the central noradrenergic system on antinociceptive effects mediated by the CB(1)-receptor agonist methanandamide, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg sc × 2, P1 and P3); zimelidine (10 mg/kg sc, 30 min pretreatment, selective serotonin reuptake inhibitor). When rats attained 10 weeks of age, monoamine and their metabolite concentrations were determined in the frontal cortex, thalamus, and spinal cord by an HPLC/ED method. Antinociceptive effects after methanandamide (10 mg/kg ip) apply were evaluated by a battery of tests. In addition, immunohistochemistry and densitometric analysis of the cannabinoid CB(1) receptor in the rat brain was performed. DSP-4 lesioning was associated with a reduction in norepinephrine content of the frontal cortex (>90 %) and spinal cord (>80 %) with no changes in the thalamus. Neonatal DSP-4 treatment produced a significant reduction in the antinociceptive effect of methanandamide in the tail-immersion test, hot-plate test and writhing tests. In the paw pressure and formalin hind paw tests results were ambiguous. These findings indicate that the noradrenergic system exerts a prominent influence on analgesia acting via the cannabinoid system in brain, without directly altering CB(1) receptor density in the brain.

Antinociceptive effect of lidocaine in rats.

Lidocaine, a local anesthetic drug, exerts its effect by blocking sodium channels in peripheral sensory neurons. It is commonly used in clinical practice as a local anesthetic drug. This study was undertaken in order to determine the effect of lidocaine on sodium channels in neurons of the central nervous system and its modulatory effect on the pain perception in rats. Therefore, the effect of direct lidocaine administration icv on pain perception in rats exposed to noxious thermal stimuli was determined. A significant long-lasting antinociceptive effect of lidocaine injected at the doses ranging between 0.065-1.3 micromol (17.5-351 microg, respectively) was documented. It was concluded that intracerebral administration of sodium channel blockers might be a useful method in the study of pain perception in the brain.

Function of heart muscle in people chronically exposed to lead.

Rhythm and conductivity disturbances in heart muscle, change in autonomic system function and raised arterial blood pressure have been described in workers exposed to lead. They may be accompanied by changes in echocardiography test and accordingly we undertook this investigation. The study population included employees of zinc and lead steelworks in the south of Poland that were divided into 2 groups: exposed to lead compounds (n=88) and the reference group - administration workers (n=55) with normal levels of lead concentration in blood (PbB) and zinc protoporphyrin in blood. Left ventricular enddiastolic dimension (LVDd), interventricular septal and posterior wall thickness, right ventricular diastolic, left atrium diameter, aortic diameter and left ventricular ejection fraction (EF) in echocardiograms were performed. Left ventricular mass LVM (g) and left ventricular mass index LVMI (g/m(2)) was calculated. In the group exposed to lead, EF decreased by 3 %, increased LVDd by 6 %, and raised LVM by 11 % and LVMI by 10 %. There was a positive relation between PbB and LVDd (R=0.18) and between PbB and LVM (R=0.14). Decreased EF, enlargement of the left ventricle and raised left ventricle mass in research undertaken, may be a result of raised arterial blood tension.

Distribution of 125I-labeled [2-8]-leucopyrokinin, active analog of leucopyrokinin in rats.

The brain and internal organs distribution of 125I-labeled [2-8]-leucopyrokinin ([2-8]-LPK), a truncated analog of leucopyrokinin (LPK), an insect myotropic peptide injected into the lateral brain ventricle was determined in rats. A high accumulation of this analog in adrenals and in the hypothalamus and hippocampus of the brain was found. A lesser but significant [2-8]-LPK accumulation in other internal organs and parts of the brain was also observed. The results of the present study confirm results of our previous study performed on the distribution of labeled native LPK in rats. A possible significance of obtained results for the brain function was discussed.

Leucopyrokinin (LPK) analog [d-Ala(5)]-[2-8]-LPK inhibits LPK-induced analgesia in rats.

It has been previously found in our laboratory that insect neuropeptide leucopyrokinin and [2-8]-leucopyrokinin, a truncated analog without the first aminoacid of leucopyrokinin peptide chain exert an antinociceptive effect in rats. The present study confirmed our previous results, and moreover it has been found that [d-Ala(5)]-[2-8]-leucopyrokinin, an analog of leucopyrokinin antagonized the antinociceptive effect of leucopyrokinin and of [2-8]-leucopyrokinin. We conclude that this synthetic analog is a probable leucopyrokinin antagonist.