Monika Rykaczewska-Czerwińska

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-1β, IFN-γ, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, 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-1β, IL-6, TNF-α, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-β1, 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.

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.

The effect of the leucopyrokinin analogue: [2-8]-leucopyrokinin on central opioid receptors in rats.

The antinociceptive effect of intracerebroventricular injections of [2-8]-leucopyrokinin (LPK), a truncated leucopyrokinin analogue, was determined in rats, by means of a tail immersion test. We found a significant antinociceptive effect of three i.c.v. doses of [2-8]-LPK: 1, 5 and 10 nmol. Pre-treating animals with naloxone hydrochloride (1 mg/kg i.p.) completely blocked the effect of two high doses of [2-8]-LPK. To determine the sub-types of opioid receptors involved in [2-8]-leucopyrokinin-induced analgesia we injected specific blockers of mu-, delta- and kappa-receptors namely, beta-funaltrexamine hydrochloride, naltrindole hydrochloride and nor-binaltorphimine dihydrochloride, respectively, prior to [2-8]-leucopyrokinin at equimolar doses. We conclude that the antinociceptive effect of [2-8]-leucopyrokinin is mediated mainly by central mu- and delta-opioid receptors.

Leucopyrokinin (LPK) analog [d-Ala5]-[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.