Effect of the nervous system on cancer: Analysis of clinical studies.

Preclinical data have shown that neurotransmitters released in peripheral tissues from nerve endings may influence carcinogenesis, affect the tumor microenvironment, and directly potentiate both proliferation and migration of cancer cells. This stimulatory role of the nervous system in cancer initiation and progression has also been documented by clinical studies investigating the effect of attenuated signaling from nerves innervating cancer tissue. However, compared to preclinical studies, clinical studies are rarer and some of them have ambiguous results. In this retrospective analysis, to assess the effect of the nervous system on cancer, we analyzed published clinical studies investigating the incidence of cancer in patients with spinal cord injury or pheochromocytoma. Our findings support a concept of the neurobiology of cancer based on the assumption that the nervous system affects cancer initiation and progression (Ref. 60). Keywords: cancer, neurobiology of cancer, norepinephrine, sympathetic nervous system, spinal cord injury, pheochromocytoma.

Oxytocin Modulates Expression of Neuron and Glial Markers in the Rat Hippocampus.

Neuropeptides including oxytocin belong to the group of factors that may play a role in the control of neuronal cell survival, proliferation and differentiation. The aim of the present study was to investigate potential contribution of oxytocin to neuronal differentiation by measuring gene and protein expression of specific neuron and glial markers in the brain. Neonatal and adult oxytocin administration was used to reveal developmental and/or acute effects of oxytocin in Wistar rats. Gene and protein expression of neuron-specific enolase (NSE) in the hippocampus was increased in 21-day and 2-month old rats in response to neonatal oxytocin administration. Neonatal oxytocin treatment induced a significant increase of gene and protein expression of the marker of astrocytes - glial fibrillary acid protein (GFAP). Oxytocin treatment resulted in a decrease of oligodendrocyte marker mRNA - 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) - in 21-day and 2-month old rats, while no change of CD68 mRNA, marker of microglia, was observed. Central oxytocin administration in adult rats induced a significant increase of gene expression of NSE and CNPase. The present study provides the first data revealing the effect of oxytocin on the expression of neuron and glial markers in the brain. It may be suggested that the oxytocin system is involved in the regulation of development of neuronal precursor cells in the brain.

Dental pulp mesenchymal stem/stromal cells labeled with iron sucrose release exosomes and cells applied intra-nasally migrate to intracerebral glioblastoma.

We report on a simple iron oxide (Venofer) labeling procedure of dental pulp mesenchymal stem cells (DP-MSCs) and DP-MSCs transduced with yeast cytosinedeaminase::uracilphosphoribosyltransferase (yCD::UPRT-DP-MSCs). Venofer is a drug approved for intravenous application to treat iron deficiency anemia in patients. Venofer labeling did not affect DP-MSCs or yCD::UPRT-DP-MSCs viability and growth kinetics. Electron microscopy of labeled cells showed internalized Venofer nanoparticles in endosomes. MRI relativity measurement of Venofer labeled DP-MSCs in a phantom arrangement revealed that 100 cells per 0.1 ml were still detectable. DP-MSCs or yCD::UPRT-DP-MSCs and the corresponding Venofer labeled cells release exosomes into conditional medium (CM). CM from yCD::UPRT-DP-MSCs in the presence of a prodrug 5-fluorocytosine caused tumor cell death in a dose dependent manner. Iron labeled DP-MSCs or yCD::UPRT-DP-MSCs sustained their tumor tropism in vivo; intra-nasally applied cells migrated and specifically engrafted orthotopic glioblastoma xenografts in rats.

Exaggerated activity of HPA axis in obese rats fed normocaloric liquid nutrition.

Experimental and clinical studies have shown alterations in activity of systems responsible for neuroendocrine stress response in obese individuals. Therefore we investigated the effect of palatable normocaloric liquid nutrition (Fresubin) on alterations in activity of the hypothalamic-pituitary-adrenal (HPA) axis in male Wistar rats of different developmental stages. Control rats (CON) received standard pellet chow all the time from weaning (21st day of age) to 150 days. Fresubin was administered throughout the experiment (LN), only in juvenility (from 21st to 90th day of age; LNJ) or only in adulthood (from 90th to 150th day of age; LNA). Body weight and energy intake were periodically monitored. Adrenal gland and fat tissue weight and plasma corticosterone levels (CORT) was determined after sacrification. Fresubin intake induced obesity in LN and LNA rats. In LN and LNA rats were observed elevated serum CORT levels, but only in LN rats with significant twofold increase compared to LNJ rats. However, the weight of adrenal glands did not differ between LN, LNJ and LNA experimental groups. Based on our results, we suggest, that obesity induced by Fresubin in LN and LNA rats is accompanied by increased HPA activity represented by elevated plasma CORT levels in these rats.

Neurobio-logy of multiple myeloma and its therapeutical use - results of the pilot study with a control arm.

BACKGROUND: Myeloma cells, occupying a bone marrow niche, are influenced not only by neighbouring stroma cells but also by signals from the axons of sympathetic nervous system. The nervous system is directly involved in the process of myeloma progression. Among other cancers, patients with myeloma suffer the most difficult distress generating intensive adrenergic signals, causing its further progression. There is a question arising from these facts regarding whether psychological interventions, modulating a function of the nervous system, can further improve outcomes of myeloma treatments. We focus on interactions between myeloma cells and the nervous system. PATIENTS AND METHODS: Twelve patients with monoclonal gamapathy of indetermined significance (MGUS) or myeloma have participated in this study; eight in the interventional arm with the intervention of forgiveness therapy and four in the control arm. The patients were in various phases of their treatment, from active observation to immuno-chemotherapy and autologous stem cell transplant. Two major types of parameters were measured during the intervention: parameters of the activity of the disease (MGUS or myeloma) and psycho-neuro-immunological parameters of the patient, such as psychological depression, anxiety, and anger by the validated test PROMIS), as well as activity of the autonomic nervous system by heart rate variability, and immune profile by flow cytometry of peripheral blood. RESULTS: Patients who completed the forgiveness intervention showed improvement of depression, anxiety, and anger measured by PROMIS above population average, significant expansion of physiological plasma cells CD138+38+ (P = 0.04), B memory lymphocytes CD27+ (P = 0.02), and dendritic plasmacytoid cells CD123+ (P = 0.03). Parameters of heart rate variability such as parasympatic nervous system (PNS) index, sympatic nervous system (SNS) index, stress index, standard deviation of NN intervals (SDNN) and root mean square of the successive differences (RMSSD) had improved in a majority of patients. CONCLUSION: An intervention centered on forgiveness therapy was able to improve distress, reduce adrenergic signals in the autonomic nervous system, and restore parameters of the immune profile of patients with plasma cell dyscrasia who suffered from chronic stress caused by repressed anger and unforgiveness. Integrative treatment of myeloma can improve the quality of life of patients and thus affect the efficiency of immuno-chemotherapy. New randomised trials are warranted to test the integrative treatment of myeloma that might be able to improve overall survival.

Neurobiology of cancer - the role of cancer tissue innervation.

BACKGROUND: Experimental and clinical studies have shown that the nervous system also plays an important role in the processes of carcinogenesis, cancer cell proliferation, and metastasis. These studies, focused on the neurobio-logical aspects of cancer, elucidate the mechanisms and pathways by which the nervous system affects tumor macro- and microenvironment. The modulatory effect of the nervous system on the tumor microenvironment is significantly mediated by nerves that innervate cancer tissue. The innervation of cancer tissue is already an accepted fact, and several authors consider it to be another hallmark of cancer. PURPOSE: The aim of this review article is to present a recent data about the role of innervation of cancer tissue, as well as to describe therapeutic consequences. CONCLUSION: Based on recent data, it can be concluded that the innervation of cancer tissue represents an important factor in the etiopathogenesis of cancer as well as a potential target for new therapeutic interventions in cancer patients.

Activation of different neuronal phenotypes in the rat brain induced by liver ischemia­reperfusion injury: dual Fos/neuropeptide immunohistochemistry.

The aim of the present study was to reveal the effect of liver ischemia­reperfusion injury (LIRI) on the activity of selected neuronal phenotypes in rat brain by applying dual Fos-oxytocin (OXY), vasopressin (AVP), tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), corticoliberine (CRH), and neuropeptide Y (NPY) immunohistochemistry. Two liver ischemia­reperfusion models were investigated: (i) single ligation of the hepatic artery (LIRIa) for 30 min and (ii) combined ligation of the portal triad (the common hepatic artery, portal vein, and common bile duct) (LIRIb) for 15 min. The animals were killed 90 min, 5 h, and 24 h after reperfusion. Intact and sham operated rats served as controls. As indicated by semiquantitative estimation, increases in the number of Fos-positive cells mainly occurred 90 min after both liver reperfusion injuries, including activation of AVP and OXY perikarya in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and TH, NPY, and PNMT perikarya in the catecholaminergic ventrolateral medullar A1/C1 area. Moreover, only PNMT perikarya located in the A1/C1 cell group exhibited increased Fos expression 5 h after LIRIb reperfusion. No or very low Fos expression was found 24 h after reperfusion in neuronal phenotypes studied. Our results show that both models of the LIRI activate, almost by the same effectiveness, a number of different neuronal phenotypes which stimulation may be associated with a complex of physiological responses induced by (1) surgery (NPY, TH, PNMT), (2) hemodynamic changes (AVP, OXY, TH, PNMT), (3) inflammation evoked by ischemia and subsequent reperfusion (TH), and (4) glucoprivation induced by fasting (NPY, PNMT, TH). All these events may contribute by different strength to the development of pathological alterations occurring during the liver ischemia­reperfusion injury.

Chemical sympathectomy suppresses fibrosarcoma development and improves survival of tumor-bearing rats.

Both experimental and clinical data indicate that the sympathetic nervous system may affect the development of certain tumors. To test this, in the present study we combined in vivo and in vitro approaches to study the effect of the sympathetic nervous system on proliferation of BP6-TU2 fibrosarcoma cells. First, we investigated the effect of 6-hydroxydopamine-induced sympathectomy on tumor development and survival of tumor-bearing rats. One week after chemical sympathectomy, we injected the BP6-TU2 fibrosarcoma cells intraperitoneally into male Wistar rats. The sympathectomy significantly reduced the incidence of intraperitoneal tumors and resulted in significantly improved survival of tumor-bearing rats compared to those with intact sympathetic innervation. Using immunohistochemical methods, we found neuron-specific enolase immunopositive structures within fibrosarcoma tissue, indicating innervation of tumors. Finally, an in vitro study showed elevated proliferation of BP6-TU2 fibrosarcoma cells in response to adding norepinephrine to the culture medium. Our findings indicate that sympathetic nerves directly potentiate the proliferation of BP6-TU2 fibrosarcoma cells in rats.

[The role of central nervous system in etiopathogenesis of peripheral organ diseases]. / Uloha centrálneho nervového systému v etiopatogenéze chorôb periférnych orgánov.

Current research on the etiopathogenesis of diseases of peripheral organs is primarily focused on the study of processes affecting those organs directly altered by diseases. As a result, therapeutic interventions are focused on the cells of those organs affected by pathological processes. However, pathological processes are not restricted to any "circumscribed" group of cells. Cells of tissue affected by pathological process interact with cells in the surrounding tissues. Moreover, pathologic processes also induce changes in the activity of the neuroendocrine and immune systems, which also affect the progression of pathological processes. The neurobiological view of diseases is based on the assumption that the nervous system processes signals related to pathological processes in peripheral organs and then consequently modulates it via the autonomic, neuroendocrine, and neuroimmune regulations. The aim of this paper is to explain the basis of the neurobiological view of diseases of the peripheral organs, and then discuss possible therapeutic consequences.

Role of the parasympathetic nervous system in cancer initiation and progression.

The nervous system plays an important role in cancer initiation and progression. Accumulated evidences clearly show that the sympathetic nervous system exerts stimulatory effects on carcinogenesis and cancer growth. However, the role of the parasympathetic nervous system in cancer has been much less elucidated. Whereas retrospective studies in vagotomized patients and experiments employing vagotomized animals indicate the parasympathetic nervous system has an inhibitory effect on cancer, clinical studies in patients with prostate cancer indicate it has stimulatory effects. Therefore, the aim of this paper is a critical evaluation of the available data related to the role of the parasympathetic nervous system in cancer.

Diastolic blood pressure as a major determinant of tissue perfusion: potential clinical consequences.

Blood pressure measuring represents a routine investigation in general medicine. In the last decades large studies have determined average blood pressure values all around the world. Large clinical trials have shown that blood pressure reduction irrespective of the used type of therapeutic intervention reduces mortality. Based on the outcomes of these trials current guidelines for hypertension encourage more "aggressive" hypertension treatment compared to recommendations from the past. In clinical practice blood pressure is sometimes reduced even below normotensive values (at least in comparison with pre-treatment levels). However there is evidence that achieving too low levels of diastolic blood pressure during antihypertensive treatment has undesirable effects. Especially in the elderly a diastolic blood pressure reduction below 70 mm Hg should be avoided, because it is associated with increased mortality. A possible explanation of this phenomenon could be that antihypertensive treatment disequilibriates the balance between sufficient perfusion pressure and arteriolar vasodilation, both of which are required for adequate tissue perfusion. Impaired microcirculation, especially in the coronary bed may account for the increased mortality in hypertensive patients with low diastolic blood pressure levels. Thus we support the idea of cautious blood pressure reduction in the elderly. Furthermore, we suggest, that monitoring the level of tissue perfusion in treated hypertensive patients might help to provide individually tailored therapy (Fig. 1, Ref. 9). Full Text (Free, PDF) www.bmj.sk.

[The complexity of interactions of the tumour growth process]. / Komplexita interakcií nádorového procesu.

It was believed for rather a long time that the only components of tumour tissue are transformed cells characterised by hyper-proliferation, invasivity and immortalisation. Therapeutic strategies thus focused on autonomous proliferation and tumour cell survival. These result from oncogene activation and inactivation of tumour-suppressor genes. Research studies showed that tumour growth itself is a complex process. In addition, studies confirmed involvement of heterotypical multicellular interactions in tumour tissue. Complexity as a characteristic is one of the processes that do not demonstrate attributes of linear systems. The process of tumour growth involves certain patterns that cannot be classified according to duration and sequence. Consequently, tumour growth can be viewed as a process with features typical for complexity. From this perspective, tumour environment consists of a range of cells, such as endothelial cells and their progenitor cells, pericytes, fibroblasts, tumour-associated fibroblasts, myofibroblasts, smooth muscle cells, mast cells, T- and B-lymphocytes, neutrophils, eosinophils, basophils, NK-cells and several different forms of macrophages. At present, well-founded assumptions exist that in-depth study of intra-tumour environment might lead to formulation of new principles in tumour biology as well as introduction of new therapeutic strategies. Research into details oftumour microenvironment is needed to expand scientific knowledge as well as to, subsequently, define tumour biomarkers. Monitoring of these biomarkers will facilitate molecular diagnostics. Biomarkers will be widely used to monitor tumour growth as well as to monitor the process of treatment. Monitoring of combinations of biomarkers will enable more detailed characterisation of tumour microenvironment. These might include, apart from receptors, signal molecules, growth factors and molecules accelerating apoptosis, specific molecules as well as their combinations or neoangiogenesis or tumour innervation parameters. Tumour complexity involves not just intracellular environment but also intracellular relationships and associations between cells and extracellular tumour components. Detection of circulating tumour cells represents another parameter to be monitored. Low-molecular weight fluorescent dyes will very likely be used for their detection. It can be assumed that circulating tumour cells will be used as markers of prognosis as well as indicators of malignity progression and treatment. Scientific advances in this area will facilitate individualised therapy of patients suffering from cancers. The aim of the present review study was to analyze scientific knowledge from the perspective of acceptance of complexity and heterogeneity of each tumour. We perceived processing of the vast amounts of literature as meaningful with respect to recognition of new knowledge and theoretical preparation for expected changes in diagnostics and treatment of tumours. We believe that the presented findings are a useful step towards achievement of comprehensive insight into tumour microenvironment.

Neurofibroma of the vagus nerve in the cervical portion.

OBJECTIVE: Neurofibromas of the vagus nerve on the neck are very rare. They are asymptomatic, slowly growing. We have seen only one case of neurofibroma of the vagus nerve in the mentioned location during last 22 years. CLINICAL PRESENTATION: 33-year-old patient with negative family history. She has observed increasing swelling on the right side of the neck for about 2 years. She complained of the disorders of swallowing, expectoration, aspiration episodes, strider, intermittent palpitations, breathlessness, frequent airway infections. Magnetic resonance (MR) and angiography (AG) showed expansion in the mentioned location. CONCLUSION: We present our experiences with neurosurgical management of neurofibroma of the vagus nerve in the cervical portion using microscopic technique. We found only 9 described cases of surgical treatment of the neurofibroma of the vagus nerve in the neck location in available literature till 2007 (Fig. 6, Ref. 9).

[Essential hypertension--syndrome, or compensatory mechanism]. / Esenciálna hypertenzia ako syndróm alebo kompenzacný mechanizmus?

Diagnosis of essential hypertension is created per exclusionem--with exclusion of all, so called secondary hypertensions (nephrogenic, endocrine conditioned etc). Idea and the name-essential hypertension are unclear. We have a lot of hypotheses about mechanisms of hypertension but no one is explaining satisfactorily the "fixation" of hypertension. From this point of view essential hypertension looks more like a syndrome than disease sui generis. Authors analyzed all possible pathways of hypertension origin as well as compensatory mechanisms in peripheral circulation in effort to reach relevant tissue perfusion. If these mechanisms lead to salt and water retention the best mode of the treatment would be to influence volume and blood vessels lumen. It is clear that optimization of blood pressure is advantageous for prevention of vascular catastrophes (myocardial and cerebral infarction). Nevertheless inadequate lowering of the peripheral tissue perfusion (kidney, CNS) can lead to degenerative changes in tissues and to disturbances in centrally regulated processes of blood pressure.

The peripheral noradrenergic terminal as possible site of action of salsolinol as prolactoliberin.

Salsolinol, an endogenous isoquinoline, induces selective prolactin release in rats [Tóth, B.E., Homicskó, K., Radnai, B., Maruyama, W., DeMaria, J.E., Vecsernyés, M., Fekete, M.I.K., Fülöp, F., Naoi, M., Freeman, M.E., Nagy, G.M., 2001. Salsolinol is a putative neurointermediate lobe prolactin releasing factor. J. Neuroendocrinol. 13, 1042-1050]. The possible role of dopaminergic and adrenergic signal transduction was investigated to learn the mechanism of this action. The effect of salsolinol (10mg/kg i.v.) was inhibited by reserpine treatment (2.5mg/kg i.p.) and reinstated by pretreatment with monoamine oxidase inhibitor (pargyline 75 mg/kg i.p.). Salsolinol did not affect the in vitro release of dopamine (DA) in the median eminence, and did not inhibit the L-DOPA induced increase of DA level in the median eminence. 1-Methyl dihydroisoquinoline (1MeDIQ) is an antagonist of salsolinol induced prolactin release and causes increase in plasma NE level [Mravec, B., Bodnár, I., Fekete, M.I.K., Nagy, G.M., Kvetnansky, R., 2004. An antagonist of prolactoliberine induces an increase in plasma catecholamine levels in the rat. Autonom. Neurosci. 115, 35-40]. Using tissue catecholamine contents as indicators of the interaction between salsolinol and 1MeDIQ we found no interaction between these two agents to explain the changes in prolactin release in the median eminence, lobes of the pituitary, superior cervical and stellate ganglion. Increasing doses of salsolinol caused a dose dependent decrease of tissue dopamine concentration and increase of NE/DA ratio in the salivary gland, atrium and spleen. These changes of DA level and NE/DA ratio run parallel in time with the increase of prolactin release. 1MeDIQ antagonized the increase of prolactin release and decrease of tissue DA content caused by salsolinol. Neither this increase of prolactin secretion nor the decrease of DA level in spleen could be demonstrated in NE transporter (NET) knock out mice. The results presented argue for the possible role of peripheral norepinephrine release as a target for salsolinol in its action releasing prolactin. The dominant role of norepinephrine transporter may be suggested.

Prefrontal cortex and dorsomedial hypothalamus mediate food reward-induced effects via npas2 and egr1 expression in rat.

The effects of food reward on circadian system function were investigated in the hypothalamic nuclei, prefrontal cortex and liver. Food rewards of small hedonic and caloric value were provided for 16 days 3 h after light phase onset to male Wistar rats. The daily pattern of locomotor activity was monitored. Gene expression profiling performed in the dorsomedial hypothalamus (DMH) and liver at the time of reward delivery indicated transcriptional factors egr1 and npas2 as possible mediators of food reward effects. Candidate genes were measured in the suprachiasmatic nuclei (SCN), DMH, arcuate nucleus (ARC), prefrontal cortex (PFC) and liver along with per2 expression. A daily pattern in glycemia and per2 expression in the SCN was emphasized by food reward. The expression of egr1 was rhythmic in the SCN, DMH, PFC and liver and food reward weakened or diminished this rhythm. The expression of npas2 was rhythmic in all tissues except for the PFC where food reward induced rhythm in npas2 expression. Food reward induced npas2 and egr1 expression in the DMH at the time of reward delivery. We suppose that the DMH and PFC participate in the adjustment of the circadian system to utilize food reward-induced input via egr1 and npas2 expression.

Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments.

Catecholamine (dopamine, norepinephrine and epinephrine) synthesizing neurons are widely distributed in the brain, sympathetic ganglia and throughout peripheral organs. Results of several recent experiments clearly suggest that many of these neurons can also contain 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), a derivate of dopamine. However, direct proof of salsolinol synthesis in those neurons is still missing. The data obtained with administration of exogenous salsolinol strongly indicate that it may play an important role in catecholaminergic regulatory processes, such as the regulation of prolactin release and/or neuronal transmission in sympathetic ganglia. Several recent data have also indicated a relationship between salsolinol or its metabolites and the etiology of Parkinson's disease or neuropathology of chronic alcoholism. These seemingly different roles of salsolinol will be discussed separately, but some common features will also be highlighted. Based on all of the discussed data the existence of a "salsolinolergic" system using salsolinol as a neuromodulator, which may be present in catecholamine synthesizing neurons, is postulated.

Complex intracardiac nervous system.

The heart is an organ with continuous activity, which must satisfy demands of an organism on various conditions. Therefore, heart activity is modulated at many levels, including intrinsic regulatory mechanisms, humoral factors and autonomic nervous system. The regulation of heart activity by sympathetic and parasympathetic nervous system is well known. Accumulated evidence in recent decades indicates that intracardiac neurons can also significantly regulate heart activity. These neurons are concentrated in multiple heart ganglia. Interactions between neurons within intracardiac ganglia together with interconnections between individual ganglia provide anatomical and functional basis of complex nervous network of the heart. This complex intracardiac nervous system together with extracardiac autonomic neurons, innervating heart, provides modulation of heart activity during both physiological and pathological conditions. This review article summarizes recent knowledge about the role of heart neurons in physiological conditions and in etiopathogenesis of selected diseases. Effect of pharmacological and surgical interventions on heart neurons is also discussed (Fig. 2, Ref. 70).

Does vagus nerve constitute a self-organization complexity or a "hidden network"?

The vagus nerve provides wide visceromotor and viscerosensory innervation of internal organs. Findings accumulated in last years suggest that vagus nerve participates on regulation of much wider spectrum of functions than described previously. Many different studies provide plausible evidence that vagus nerve importantly participates not only in transmission of information from inflamed tissues, but also in efferent modulation of inflammatory processes. Moreover, there are some findings supporting the hypothesis that vagus nerve might participates in monitoring and modulation of tumorigenesis. Electrical stimulation of the vagus nerve is used as a treatment of epilepsy. Moreover, data also suggest a beneficial effect of electrical stimulation of the vagus nerve in patients with depression, anxiety, migraine and Alzheimer's disease. We suggest, that the vagus nerve might constitute a highly differentiated complex system which modulates various functions. Moreover, we propose that the vagus nerve as a complex system might participate in constitution of a biological compartment of conscious. In this article we discuss findings and ideas supporting these hypotheses (Ref. 73).

Chronic polysystemic candidiasis as a possible contributor to onset of idiopathic Parkinson's disease.

The underlying cause of Parkinson's disease is still enigma. Several mechanisms have been implicated in the etiopathogenesis of PD including oxidative damage, environmental toxins, genetic predisposition, and accelerated aging. Recent research suggests that salsolinol, a derivate of dopamine, is an important contributing factor. In the presence of acetaldehyde dopamine is converted into salsolinol, a neurotoxin involved in apoptosis of dopaminergic neurons. Increased production of acetaldehyde is associated with chronic polysystemic candidiasis (CPC). Chronically elevated levels of acetaldehyde in patients with CPC might participate in the formation of salsolinol and its metabolites in the brain contributing to the destruction of dopaminergic cells in substantia nigra. Clinical mental symptoms of PD often correspond with the mental manifestations of CPC. This hypothesis may constitute basis for further scientific and clinical research of PD etiopathogenesis (Fig. 1, Ref. 29).