Wojciech Roczniak

Toxic influence of subchronic paraquat administration on dopaminergic neurons in rats.

Paraquat is a toxin suggested to contribute to pathogenesis of Parkinsons disease. The aim of the present study was to examine toxic influence of subchronic treatment with this pesticide (5 days, one injection per day, 2-3 days of withdrawal) on dopaminergic, serotonergic, noradrenergic and GABAergic neurons. Paraquat decreased the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra by 22% (measured 3 days after withdrawal). Two days after withdrawal the levels of the dopamine metabolites and dopamine turnover in the caudate-putamen, substantia nigra and prefrontal cortex were reduced by ca. 20-60%, and the binding of [(3)H]GBR 12,935 to dopamine transporter dropped by 25-40% in the caudate-putamen. Three days after paraquat withdrawal, the level of dopamine in the caudate-putamen was significantly increased, and earlier decreases in DOPAC and HVA in the substantia nigra, as well as [(3)H]GBR 12,935 binding in the caudate-putamen were reversed. Moreover, an increase in serotonin turnover in the caudate-putamen and prefrontal cortex, and noradrenaline level in the former structure was observed 2-3 days after paraquat withdrawal. Three days after the last paraquat injection 24-35% decreases in the proenkephalin mRNA levels and 5-7% reduction in glutamic acid decarboxylase (GAD)67 mRNA were found in the caudate-putamen. The present study suggests that subchronic paraquat administration triggers processes characteristic of early stages of dopaminergic neuron degeneration, and activates compensatory mechanisms involving dopaminergic, noradrenergic, serotonergic and GABAergic transmissions.

Histamine H3 receptor ligands modulate L-dopa-evoked behavioral responses and L-dopa-derived extracellular dopamine in dopamine-denervated rat striatum

To explore a recently established association between histaminergic and dopaminergic neuronal phenotypic systems in brain, we determined the effect of the respective histaminergic H3 receptor agonist and antagonist/inverse agonist, imetit and thioperamide, on L-DOPA — derived tissue and extracellular dopamine (DA) and metabolite levels in the striatum of 6-hydroxydopamine (6-OHDA) - lesioned rats (i.e., parkinsonian rats). We also examined the influence of histamine H3 ligands on L-DOPA evoked behavioral responses (locomotor activity, number of rearings, stereotyped behavior and motor coordination). Using HPLC/ED andin vivo microdialysis technique, imetit (5 mg/kg, i.p.) but not thioperamide (5 mg/kg, i.p.) was shown to attenuate an L-DOPA-evoked (15 mg/ kg, i.p.; carbidopa, 30 min pretreatment) increase in extracellular DA in the neostriatum of 6-OHDA-lesioned rats. However, both imetit and thioperamide increased microdialysate levels of DOPAC and HVA, probably by enhancing intraneuronal DA utilization. As indicated by neurochemical analysis of the striatum imetit produced a decrease in tissue DA content. These findings support the hypothesis that central H3 histaminergic receptors have a modulatory role in the storage, metabolism and release of DA derived from exogenous L-DOPA challenge. Furthermore, evidence from behavioral studies indicate that histamine H3 receptor block markedly improved motor coordination. Conversely, histamine H3 receptor stimulation, being without effect on motor coordination, enhanced vertical activity in rats. From the above we conclude that histamine H3 agonism may augment motor dyskinesia in Parkinson’s disease (PD) patients and presumably worsen L-DOPA therapy. Consequently, the histaminergic system represents a viable target for modulating the effectiveness of L-DOPA therapy in Parkinson’s disease.

New insights into the pathogenesis and treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGID), characterized by abdominal pain and a change in stool form that cannot be explained by structural abnormalities. Its prevalence ranges from 9 to 23% of the worldwide population. The pathophysiology of IBS is diverse and not well understood. Biopsychosocial concept assumes that the disease is a product of psychosocial factors and altered at multiple levels of gut physiology interactions. Some aetiological factors have been identified, yet. One of the most important is the disruption of brain-gut mutual communication that leads to visceral hypersensitivity. Also genetic and epigenetic factors are involved. Chronic stress may predispose to IBS as well as exacerbate its symptoms. Both quantitative and qualitative disorders of the gut microbiota are observed. There is also a relationship between the IBS symptoms and the intake of a specific type of food products. In the diarrhoea type of IBS the role of previous gastrointestinal infection is demonstrated. Recent studies have suggested that visceral hypersensitivity in patients with IBS may be secondary to the activation of the immune cells and low-grade inflammation. Clinical symptoms of IBS include abdominal pain and change in bowel habits as well as somatic and psychiatric comorbidities. IBS is diagnosed on the basis of Rome Diagnostic Criteria. Recently, their newest version (Rome IV) has been presented. The aim of this review is to summarize the past decade progress in IBS diagnosis, main pathophysiological aspects and therapeutic management strategy.

The effect of central noradrenergic system lesion on dopamine (DA) and serotonin (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in chosen parts of the rat brain.

INTRODUCTION Since little has been known about the effect of the central noradrenergic system on the reactivity of serotonin 5-HT3 receptors, the aim of the current study was to find out whether this reactivity could be altered by chemical damage to the system in adult rats in early developmental stage. MATERIALS AND METHODS Adult male Wistar rats with central noradrenergic lesion induced by DSP-4 on day 1 and 3 of life were injected with analgesic model substance - morphine, serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide, PBG), 5-HT3 receptor antagonist (ondansetron) or both compounds jointly followed by decarboxylase inhibitor of aromatic amino acids (NSD-1050). After 30 min following NSD-1050 injection, the animals were decapitated using a guillotine. Chosen cerebral structures were dissected, and the contents of 5-hydroxytryptofan (5-HTP) and l-dihydroxyphenylalanine (l-DOPA) were determined using high-pressure liquid chromatography with electrochemical detection (HPLC/ED). RESULTS Neither PBG nor morphine affected l-DOPA contents in the hippocampus in control rats; however, DSP-4 lesion caused a significant decrease in the synthesis rate of DA in this structure. Hippocampal contents of 5-HTP increased after morphine or PBG administration, and central noradrenergic lesion attenuated this effect. Morphine or PBG decreased cerebellar DA synthesis rate in control rats and DSP-4 lesion did not modify it. Cerebellar levels of 5-HTP increased after morphine or PBG challenge in control rats. DSP-4 lesion intensified the effect of morphine and attenuated that of PBG. Ondansetron abolished the effects mediated by PBG. We did not observe any impact of PBG or ondansetron on DA and 5-HT synthesis in the striatum. CONCLUSION Damage to the central noradrenergic system in rat newborns, through altered reactivity of central 5-HT3 receptors, results in permanent disorders in serotoninergic transmission in hippocampus and cerebellum as well as dopaminergic transmission in hippocampus, which may attenuate the activity of the descending pathways that derive from these structures.

Surgical method of treatment and level of satisfaction with life among women diagnosed with breast cancer, according to time elapsed since performance of surgery

INTRODUCTION In women diagnosed with breast cancer one of the methods most commonly applied in therapy is surgical treatment, which consists in a breast conserving surgery or total removal of the breast. The applied type of surgical treatment may exert an effect on the satisfaction with life of the women. OBJECTIVE The aim of the study was evaluation of the satisfaction with life among women surgically treated for breast cancer, according to the type of surgery on the breast, and the time elapsed since its performance. MATERIAL AND METHODS The study included 121 patients of the Sub-Carpathian Oncology Centre in Brzozów, south-east Poland, who had undergone surgical treatment due to breast cancer. The women expressed their informed consent to participate in the study. The method of a diagnostic survey was applied. RESULTS The women obtained a mediocre result in satisfaction with life - 5.64 sten scores. Patients who had undergone mastectomy had a considerably lower level of satisfaction with life, compared to those after breast-conserving surgery (4.73 sten scores vs. 6.30 sten scores). Evaluations of the satisfaction with life in the examined group significantly differed according to the time elapsed since performance of surgery. CONCLUSIONS There is a need for undertaking actions directed to women who have undergone surgical treatment for breast cancer within the period from 2-5 years, aimed at improving the satisfaction with life in this group of patients. In addition, special support should be provided for women who have undergone mastectomy, especially during the period of more than 1 and up to 2 years.

Growth hormone deficiency in children and young adults.

Growth hormone (GH) is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD) may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

Assessment of phytotherapeutic mixtures as a potential route of absorption of some metal compounds

Abstract Introduction. Nowadays, herbalism seems to arouse much interest. Approximately 80% of the world’s population are willingly take plant-derived drugs. It should be remembered that both herbs and their products may have not only beneficial but also harmful components. Moreover, medicinal plants frequently exhibit the capacity to selectively accumulate toxic elements. Objective. To assess the potential burden of phytotherapy with medicinal plants used in chosen herbal mixtures. Materials and method. A total of 76 species of medicinal plants from all over Poland and contained in herbal mixtures applied in selected diseases were investigated with respect to the content of heavy metals. Argon plasma atomic emission spectrometry (AES) was applied, using an ICP-ULTIMA spectrometer. Results. The study plants showed various cumulative properties, depending on plant species and the effect of environmental purity on the metal content in raw materials. Daily doses of metal absorption due to phytotherapy in various diseases were determined. The levels of Ni, Co and Cr accumulation were similar to that of Pb. Conclusions. Herbal therapies using the medicinal plants studied did not exceed daily norms of the investigated metals. However, as these metals may also occur in other food products, a prolonged use of plant-derived drugs can be an additional burden, especially in the case of renal failure.

Research into analgesic effect of ondansetron in persistent pain model in rats with central noradrenergic system lesion

Introduction. Many known substances affecting the serotoninergic system induce definite physiological effects, including those which are therapeutic. For instance, the enhanced serotoninergic transmission due to decreased functions of autoreceptors and increased inhibitory functions of postsynaptic 5-HT1A is associated with antidepressant effect. The central serotoninergic system takes part in the regulation of many bodily functions, such as sleep, wakefulness, blood pressure, pain perception or sexual behaviours. Moreover, it is involved in the pathogenesis of depression, anxiety, addictions, migraine and other headaches. In pain therapy, not only typical analgesics are used, but also substances without obvious analgesic effect, thus allowing potential pharmacological modulation of analgesic activity in the treatment of pain. Objective. The aim of the study was to determine whether a chemical lesion to the central noradrenergic system at an early stage of individual development alters reactivity of 5-HT3 receptors in adult rats. Materials and method. The study used newborn and adult Wistar rats aged 8–10 weeks. Behavioural tests (writhing test, formalin assay) were used to assess the analgesic action of ondansetron as a 5-HT3 receptor antagonist. Results. The analgesic effect of ondansetron (1.0 mg/kg b.w., i.p.) in the writhing test was weak and short. Pain intensity score after ondansetron injection (1.0 mg/kg b.w., i.p) was 2–3 points and did not differ significantly between the study

Relations between excretion of indole melanogen (TPM) and time of exposure to solar radiation

Introduction. In the human skin exposed to ultraviolet (UV) radiation, melanogenesis occurs in two stages, accompanied by urinary excretion of Thormalen-positive melanogen (TPM). In Poland, no data are available on the course and intensity of melanogonesis in relation to UV exposure in an industrial region. Material and methods. The Thormalen test was used for the collected samples (N=136) as modified by Matous and Suchoń. Results. Maximum environmental TPM content (0.67 μg/dm3) was observed in August. Conclusion. The time of UV exposure and local type of solar radiation promote melanogenesis.