Exploring a New Pathophysiological Association in Acne Vulgaris and Metabolic Syndrome: The Role of Biogenic Amines and Glutathione Peroxidase.

Background and Objectives: Metabolic disorders cause many skin issues, including acne vulgaris. This research investigated the function of glutathione peroxidase (GTPx) and biogenic amines as a potential novel pathophysiological link between metabolic syndrome (MetS) and acne vulgaris. Materials and Methods: The patients were distributed into two groups: metabolic precondition (MPG, n = 78) and control (CG, n = 81). To determine the extent of acne and metabolic preconditioning, patients were subjected to extensive clinical/paraclinical investigations. Additionally, catecholamine levels in urine and GTPx levels in blood were measured. Results: Mild acne was more common in the CG (32.1 vs. 6.4, p < 0.001), and severe acne was more common in the MPG (61.54 vs. 25.9, p < 0.001), with the average age being substantially higher in the MPG (23.81 vs. 21.05, p = 0.002). Significant variations were observed in the paraclinical levels for catecholamines (p < 0.05). In the MPG, most severe acne patients were overweight (52.1%), insulin-resistant (48.8%), or obese (47.9%). Moderate acne was most often linked to obesity (56%), overweight (44%), and insulin resistance (20%). Patients with severe acne (48.83%) had a considerably greater incidence of insulin resistance syndrome (p = 0.039) than those with moderate or severe acne (20%). The presence of two or three metabolic disorders considerably raised the risk of severe acne. Significant differences between groups were observed only in the subgroup of patients with severe acne, with lower values in the MPG (p = 0.015). Significant differences between groups were observed regarding the subgroup of patients with severe acne, with lower DTPx values in the MPG. At the group level, only CG patients with severe acne had reduced GTPx levels. Significant differences in catecholamine values were seen between groups (p < 0.05), independent of acne severity, except for adrenaline in mild acne patients (p = 0.059). Conclusions: The complex connection between GTPx and catecholamines in MetS suggests a significant role of these factors in the pathogenesis of acne associated with this condition, opening new perspectives in the research and treatment of acne in the context of MetS.

3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine.

Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1ß, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance.

The Neuroendocrine Neoplasms of the Digestive Tract: Diagnosis, Treatment and Nutrition.

Nuroendocrine neoplasms (NENs) are a group of rare neoplasms originating from dispersed neuroendocrine cells, mainly of the digestive and respiratory tract, showing characteristic histology and immunoprofile contributing to classification of NENs. Some NENs have the ability to produce biogenic amines and peptide hormones, which may be associated with clinical syndromes like, e.g., the carcinoid syndrome caused by unmetabolized overproduced serotonin, hypoglycemic syndrome in case of insulinoma, or Zollinger-Ellison syndrome accompanying gastrinoma. Diagnostics for these include ultrasound with endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography/computed tomography (PET/CT). Different nuclear medicine procedures can also be used, like somatostatin analogues scintigraphy (SRS) and 68Ga-Dota-Peptide PET/CT, as well as biochemical methods to determine the level of general neuroendocrine markers, such as chromogranin A (CgA), 5-hydroxyindolacetic acid (5-HIAA), synaptopfysin and cell type-specific peptide hormones, and neurotransmitters like gastrin, insulin, serotonin, and histamine. NENs influence the whole organism by modulating metabolism. The treatment options for neuroendocrine neoplasms include surgery, somatostatin analogue therapy, radionuclide therapy, chemotherapy, molecular targeted therapies, alpha-interferon therapy, and inhibitors of serotonin production. In the case of hypersensitivity to biogenic amines, a diet that limits the main sources of amines should be used. The symptoms are usually connected with histamine, tyramine and putrescine. Exogenic sources of histamine are products that take a long time to mature and ferment. Patients with a genetic insufficiency of the diamine oxidase enzyme (DAO), and those that take medicine belonging to the group of monoamine oxidases (MAO), are particularly susceptible to the negative effects of amines. Diet plays an important role in the initiation, promotion, and progression of cancers. As a result of the illness, the consumption of some nutrients can be reduced, leading to nutritional deficiencies and resulting in malnutrition. Changes in metabolism may lead to cachexia in some patients suffering from NENs. The aim of this narrative review was to advance the knowledge in this area, and to determine possibilities related to dietary support. The authors also paid attention to role of biogenic amines in the treatment of patients with NENs. We can use this information to better understand nutritional issues faced by patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and to help inform the development of screening tools and clinical practice guidelines.

[Amphibian skin as a source of therapeutic peptides]. / Peptides thérapeutiques à fleur de peau de grenouille.

The search for new bioactive molecules that could be used in therapeutics is a major public health issue, particularly in the treatment of certain diseases such as cancer. In this context the exploration of the venom of animals (snakes, amphibians, cones, scorpions, insects...) that produce molecules of various structures and biological activities, is a very promising direction. Research in this area led to the discovery of neuropeptides, hormones, toxins, antimicrobial peptides and other extremely potent mediators. These are now used in many areas both in fundamental research and in translational research, respectively, to understand biochemical and physiological mechanisms, or to use as medical diagnostic tools and for therapeutic purposes. Pr. V. Erspamer is the first researcher to have shown, in the 1930s, that in addition to biogenic amines and alkaloids, granular glands from the skin of amphibians also produced huge amounts of peptides with various structures and biological activities. He also showed that these peptides had their counterparts, most often in the form of identical or similar peptides, in the central nervous system and the gastrointestinal tract of mammals. These observations are summarized in the form of a triangle concept of "brain-gut-skin" that states that any peptide found in a compartment should be present in the other two. In addition, abundance, ease of extraction and identification of peptides from amphibian skin make this model a means to search for their counterparts in mammals where they are present in minute quantities. This approach has two advantages: (i) at the fundamental level, the large peptide diversity, ubiquity and multiplicity of functions to which they participate, constitute a true chemical library to understand the mechanisms of recognition and signal transduction and study the physicochemical basic of the specificity; and (ii) in terms of applications, the relative simplicity of these peptides and the rise of the production techniques by chemical or recombinant synthesis offer an innovative potential for the development of molecules with pharmacological or therapeutic purposes.

[On the number and morphometrical parameters of the nucleus ambiguous neurons after the injury and regeneration of the recurrent laryngeal nerve in the rat]. / Estudio del número de neuronas del núcleo ambiguo y sus parámetros morfométricos tras lesión y regeneración del nervio laríngeo recurrente de la rata.

INTRODUCTION AND OBJECTIVES: In laryngeal nerves injuries it is essential to know the morpho-functional reorganization of the neurons which supply the larynx in order to be successful with the clinical techniques of functional reinnervation and/or orthotopic transplant. Due to the lack of this type of studies in the literature, we investigated the organization of laryngeal motoneurons in the nucleus ambiguous (NA) after the axotomy and regeneration of the recurrent laryngeal nerve (RLN) in adult rats. MATERIAL AND METHODS: We used biotinylated dextran amines (BDA, 3 kDa), this fact is an innovation in the field, because this is a novel methodological approach to this model. We studied a control group of 14 animals and four experimental groups of between 10 and 16 animals each one. In the experimental groups we studied the regeneration of the axotomized nerve in four different intervals of time after the injury: 21-28 days, 42-60 days, 90-120 days, and 150-180 days. In the control group we traced the RLN without injury while in the experimental groups we traced the axotomized RLN after each regeneration interval. RESULTS: The number of traced neurons in the control group was 143 +/- 38; in the experimental groups the number was always lower than in the control (21-28 days: 14 +/- 23 neurons; 42-60 days: 46 +/- 49; 90-120 days: 55 +/- 57; 150-180 days: 61 +/- 60). The morphologic parameters studied within the neuronal bodies in the experimental groups were no statistically different when compared with those in the control group. CONCLUSIONS: Results show that the tracing of the RLN after its axotomy and regeneration, in the adult rat, involves a decrease in the number of traced neurons within the NA but no changes in their size or shape during the analysed periods.

Receptors of mammalian trace amines.

The discovery of a family of G-protein coupled receptors, some of which bind and are activated by biogenic trace amines, has prompted speculation as to the physiological role of these receptors. Observations associated with the distribution of these trace amine associated receptors (TAARs) suggest that they may be involved in depression, attention-deficit hyperactivity disorder, eating disorders, migraine headaches, and Parkinson's disease. Preliminary in vitro data, obtained using cloned receptors, also suggest a role for TAARs in the function of hallucinogens.

Trace amine receptors as targets for novel therapeutics: legend, myth and fact.

Trace amines are attracting attention as neurotransmitters because they are believed to play a role in human disorders such as schizophrenia, depression, attention deficit disorder and Parkinson's disease. Research to date is promising and confirms the need for continuing work to forge the way for new drug discovery.

Dietary bioactive peptides.

Evidence indicates that hydrolyzed protein fragments (i.e., peptides) cross the small intestine and reach peripheral tissue via the systemic circulation. Dietary peptides can have specific actions locally, on the gastrointestinal tract, or at more distant sites. These bioactive peptides can alter cellular metabolism and may act as vasoregulators, growth factors, releasing hormones, or neurotransmitters. The available nitrogen choices for enteral nutrition are free amino acids, peptides, or intact proteins. Current experimental evidence indicates that diets that possess the capability of producing luminal peptides are superior to diets lacking this capacity. The parent protein used for enteral nutrition generates specific peptides that can also dictate a variety of metabolic responses. The concept of dietary bioactive peptides offers an explanation for varying effects of diet on physiologic responses. These concepts have spurred research efforts into the possibility of enteral administration of biogenic amines.

[Aggressive role of lysosomal enzymes in gastric ulceration]. / Agressivnaia rol' lizosomnykh fermentov pri iazvoobrazovanii v zheludke.

Administration of lysosomes and lysosome enzymes into the submucous base of intact rats' stomachs did not result in ulceration. Premedication by histamine, serotonin (combined and separated) and ACTH did not increase sensibility of mucous membrane to lysosome enzymes. Prednisolone-premedication provoked the decrease of mucous membrane resistance to free lysosome enzymes and appearance of ulcerative lesions in the point of enzyme applications. Free lysosome enzymes are able to produce ulcerative lesions. This process is going on with the participation of prednisolone.

Cerebral vasospasm

Vasoespasmo cerebral ocorre em patologias como enxaqueca, hemorragia subaracnóidea, trauma de crânio, após isquemia e/ou hipoxia. A fisiopatologia do vasoespasmo cerebral nestas patologias näo está completamente desvendada. Neste artigo säo analisados os fatores neuroquímicos e morfológicos responsáveis pelo controle circulatório cerebral. As alteraçöes circulatórios que seguem a hemorragia subaracnóidea säo utilizadas como exemplo. Conclui-se que fatores bioquímicos, fisiológicos e morfológicos säo responsáveis pelas manifestaçöes vasculares que ocorrem após a hemorragia subaracnóidea. Alternativas de tratamento do vasoespasmo cerebral säo discutidas

d-Tyrosine prevents hypertension in DOCA-saline treated uninephrectomised rats.

High blood pressure in DOCA-saline treated uninephrectomised rats is prevented or even reversed by tyrosine, tyramine or by treatments which - based on circumstantial evidence - might increase local brain tyramine concentration.