Wydzielanie serotoniny i melatoniny u kobiet po menopauzie z zaburzeniami odżywiania

  Introduction: Postmenopausal women manifest emotional disorders associated with an increase in appetite. The aim of the study was to assess the serotonin and melatonin secretion and metabolism in postmenopausal women in relation to eating disorders. Material and methods: Sixty postmenopausal women and 30 women without hormonal disturbances were enrolled into the study and divided into three groups: group I (control) – women without menstrual disorders, group II — postmenopausal women without appetite disorders and change in body weight, and group III — postmenopausal women with increased appetite and weight gain. Serum melatonin, serotonin, urinary 6-sulfatoxymelatonin (aMT6s), and 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured. Results: Serum serotonin and melatonin levels in groups II and III were lower compared to group I. Urinary 5-HIAA and aMT6s excretion was lower in overweight women. In group III the correlation between the serum level of serotonin, melatonin, and BMI was negative; a high statistical significance was found between BMI and urinary aMT6s excretion. Conclusions: Melatonin supplementation and use of drugs modulating the serotonin homeostasis together with female hormones have a beneficial effect in complex treatment of disorders of eating in postmenopausal women. (Endokrynol Pol 2016; 67 (3): 299–304)    Wstęp: U kobiet po menopauzie często spotykamy zaburzenia emocjonalne oraz wzrost apetytu. Celem badań była ocena wydzielania i metabolizmu serotoniny i melatoniny u kobiet w okresie pomenopauzalnym z zaburzeniami odżywiania. Materiały i metody: Badanie przeprowadzono w grupie 60 kobiet po menopauzie i 30 przed menopauzą (grupa kontrolna). Wśród kobiet po menopauzie wyodrębniono dwie podgrupy — kobiety ze wzrostem apetytu i masy ciała oraz bez nich. Procedury diagnostyczne obejmowały ocenę stanu odżywienia, określenie stężenia melatoniny i serotoniny w surowicy krwi oraz ich matabolitów — siarczanu 6-metoksymelatoniny (aMT6s) oraz kwasu 5-hydroksy-indolooctowego (5-HIAA) w moczu. Wyniki: Stwierdzono, że stężenie serotoniny i melatoniny w surowicy krwi w grupach pacjentek po menopauzie było niższe niż u kobiet przed menopauzą. Wydalenie metabolitów serotoniny i melatoniny z moczem było najniższe u otyłych kobiet po menopauzie. U tych pacjentek stwierdzono ujemną korelację między stężeniem serotoniny w surowicy krwi, stężeniem melatoniny oraz BMI; a także istotną statystycznie zależność pomiędzy wydalaniem aMT6s z moczem a BMI. Wnioski: U kobiet w okresie pomenopauzalnym wydzielanie serotoniny i melatoniny jest zmniejszone, co należy uwzględnić w kompleksowej terapii i prewencji zaburzeń łaknienia i odżywienia. (Endokrynol Pol 2016; 67 (3): 299–304)

Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women

Wstęp: Melatonina (MEL) korzystnie wpływa na przewód pokarmowy, między innymi poprzez relaksujące działanie na mięśnie gładkie. Jej wydzielanie zmienia się wraz z wiekiem, szczególnie u kobiet w okresie pomenopauzalnym. Celem pracy była ocena wpływu melatoniny na objawy zespołu jelita nadwrażliwego w tej grupie kobiet. Materiał i metody: Do badania włączono 80 kobiet, w wieku 48&#8211;65 lat. Zgodnie z Kryteriami Rzymskimi III wyodrębniono grupę z zaparciową postacią jelita nadwrażliwego (IBS-C, n = 40) i z biegunkową postacią tej choroby (IBS-D, n = 40). Grupę porównawczą (C) stanowiło 30 kobiet zdrowych, w tym samym wieku. U wszystkich określono dobowe wydzielanie siarczanu 6-hydroksymelatoniny (6-HMS) z moczem. Pacjentki w obu grupach przyjmowały przez 6 miesięcy melatoninę (3 mg rano i 5 mg wieczorem) lub placebo. W 2,4 i 6 miesiącu oceniono nasilenie dolegliwości (bóle i wzdęcia brzucha oraz deregulację wypróżnień), używając wizualnej 10 stopniowej skali. Wyniki: Wydalanie 6-HMS z moczem (&#956;g/24 h) wynosiło odpowiednio w grupach: C &#8212; 11,4 &#177; 3,0, IBS-C &#8212; 10,2 &#177; 3,2, IBS-D &#8212; 14,0 &#177; 6,3 (p < 0,05). Stwierdzono korelację między nasileniem objawów a wydzielaniem 6-HMS: ujemną IBS-C (r = &#8211;0,714), a dodatnią w grupie IBS-D (r = 0,409). Po 6 miesiącach używania melatoniny w grupie IBS-C bóle i wzdęcia brzucha zmniejszyły się u 70% pacjentek, a zaparcia u 50% pacjentek. W grupie IBS-D poprawę uzyskano u 45% pacjentek, a wyniki nie różniły się znacząco od tych w grupie przyjmującej placebo. Wnioski: Melatonina może być stosowana w sk ojarzonej terapii IBS, szczególnie w postaci z zaparciami. (Endokrynol Pol 2013; 64 (2): 114&#8211;120)Introduction: Melatonin (MEL) exerts beneficial effects on the gut partly by myorelaxative properties upon the smooth muscle. Its secretion decreases with age, particularly in postmenopausal women. This study was aimed at evaluating the effect of MEL on the symptoms of irritable bowel syndrome (IBS) in this group of patients. Material and methods: The investigations were carried out in 80 postmenopausal women, aged 48&#8211;65 years, divided into two equal groups, diagnosed according to Rome Criteria III: i.e. patients with IBS with constipation predominant (IBS-C), and patients with IBS with diarrhoea predominant (IBS-D). The control group (C) included healthy women aged 46-65 years. In all subjects, 6-sulfatoxymelatonin (6-HMS) concentration urine was measured using ELISA assay. Patients in both groups over the course of six months were given melatonin (at a dose of 3 mg fasting and 5 mg at bedtime) or a placebo (double blind trial). Disease activity was evaluated after two, four and six months, using a ten-point scale to assess the main somatic symptoms: visceral pain, abdominal bloating, etc. Results: The amounts of 6-HMS urine excretion (&#956;g/24 h) were: C 11.4 &#177; 3.0, IBS-C 10.2 &#177; 3.2, IBS-D 14.0 &#177; 6.3 (p < 0.05). Correlation between values of symptoms score and contrary excretion of 6-HMS: IBS-C r = &#8211;0.714, IBS-D r = 0.409. After six months in the IBS-C group, the intensity of visceral pain and abdominal bloating had decreased in 70% of patients (p < 0.01) and constipation in 50% of patients (p < 0.05). Beneficial changes in the IBS-D group were noted in 45% of patients, but this was not better compared to the placebo. Conclusions: Melatonin can be used as part of the treatment of IBS, particularly in patients with constipation-predominant IBS. (Endokrynol Pol 2013; 64 (2): 114&#8211;120

Serotonin in the Pathogenesis of Lymphocytic Colitis

Lymphocytic colitis (LC) is a chronic inflammatory disease associated with watery diarrhea, abdominal pain, and colonic intraepithelial lymphocytosis. Serotonin (5-hydroxytryptamine, 5-HT) is reported to increase in certain colon diseases; however, little is known regarding its metabolism in LC. In the present work, the level of 5-HT in serum and the number of enteroendocrine cells (EECs) as well as the expression of the 5-HT rate-limiting enzyme tryptophan hydroxylase 1 (TPH1) in colonic biopsies and urine 5-hydroxyindoeoacetic acid (5-HIAA) were determined in 36 LC patients that were treated with budesonide and 32 healthy controls. The 5-HT serum and 5-HIAA urine levels were measured using ELISA, the EEC number was determined immunohistochemically, and the colonic TPH1 mRNA expression was determined using RT-PCR. The levels of 5-HT and 5-HIAA and the number of EECs were higher in LC patients than in the controls, and positive correlations were observed between the 5-HT and 5-HIAA levels, 5-HT and EEC number, TPH1 mRNA and EEC number, as well as the severity of disease symptoms and 5-HIAA. Budesonide decreased the levels of 5-HT, 5-HIAA, and TPH1 expression and the number of EECs to values that did not differ from those for controls. In conclusion, the serotonin metabolism may be important for LC pathogenesis, and the urinary level of 5-HIAA may be considered as a non-invasive marker of this disease activity.This research was funded by the Medical University of Lodz, grant number 503/6-006-0

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis1

The cooperation of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, operating in parallel in plants to generate isoprenoid precursors, has been studied extensively. Elucidation of the isoprenoid metabolic pathways is indispensable for the rational design of plant and microbial systems for the production of industrially valuable terpenoids. Here, we describe a new method, based on numerical modeling of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the cooperation of MVA and MEP reprogrammed upon osmotic stress (sorbitol treatment) in Arabidopsis (Arabidopsis thaliana). The contribution of the MEP pathway increased significantly (reaching 100%) exclusively for the dominating Dols, while for long-chain Dols, the relative input of the MEP and MVA pathways remained unchanged, suggesting divergent sites of synthesis for dominating and long-chain Dols. The analysis of numerically modeled Dol mass spectra is a novel method to follow modulation of the concomitant activity of isoprenoid-generating pathways in plant cells; additionally, it suggests an exchange of isoprenoid intermediates between plastids and peroxisomes

Konsensus dotyczący zastosowania leków hamujących wydzielanie kwasu solnego w żołądku w najczęstszych chorobach górnego odcinka przewodu pokarmowego w praktyce lekarza podstawowej opieki zdrowotnej

Niniejszy artykuł ma charakter konsensusu i dotyczy zastosowania leków antysekrecyjnych w leczeniu najczęstszych chorób górnego odcinka przewodu pokarmowego w praktyce lekarza podstawowej opieki zdrowotnej. Dwadzieścia sześć stwierdzeń, które stanowią podsumowanie obecnego stanu wiedzy na ten temat, zostało poddanych głosowaniu przez członków Zarządu Głównego Polskiego Towarzystwa Gastroenterologii (ZG PTG-E). Celem głosowania była ocena stopnia akceptacji poszczególnych stwierdzeń i gotowości do ich zalecania w polskich warunkach. Dwadzieścia jeden z 26 stwierdzeń zostało zaakceptowanych w całości lub jedynie z pewnym zastrzeżeniem (stopień poparcia A lub B) przez co najmniej 85% głosujących, a kolejne 3 uzyskały poparcie wynoszące co najmniej 74%. Wysoki stopień poparcia większości stwierdzeń zawartych w konsensusie przez członków ZG PTG-E upoważnia do stwierdzenia, że przedstawione w nim zasady wykorzystania leków antysekrecyjnych mogą być rekomendowane w praktyce lekarzy podstawowej opieki zdrowotnej w Polsce. Gastroenterologia Kliniczna 2009, tom 1, nr 1, 1-

2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation

HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action

Tryptophan Intake and Metabolism in Older Adults with Mood Disorders

The role of serotonin in the pathogenesis of depression is well-documented, while the involvement of other tryptophan (TRP) metabolites generated in the kynurenine pathway is less known. The aim of this study was to assess the intake and metabolism of TRP in elderly patients with mood disorders. Ninety subjects in three groups, 30 subjects each, were enrolled in this study: controls (healthy young adults, group I) and elderly individuals without (group II) or with (group III) symptoms of mild and moderate depression, as assessed by the Hamilton Depression Rating Scale (HAM-D) and further referred to as mood disorders. The average TRP intake was evaluated with the nutrition calculator. Urinary levels of TRP, 5-hydroxyindoleacetic acid (5-HIAA), L-kynurenine (KYN), kynurenic acid (KynA), xanthurenic acid (XA), and quinolinic acid (QA) were determined by liquid chromatography with tandem mass spectrometry and related to creatinine level. The average daily intake of TRP was significantly lower in group III than the remaining two groups, but group III was also characterized by higher urinary levels of KYN, KynA, XA, and QA as compared with younger adult individuals and elderly patients without mood disorders. Therefore, mild and moderate depression in the elderly may be associated with a lower intake of TRP and changes in its kynurenine metabolic pathway, which suggests a potential dietary TRP-based intervention in this group of patients

Changes in Tryptophan Metabolism on Serotonin and Kynurenine Pathways in Patients with Irritable Bowel Syndrome

(1) Background: L-tryptophan is a substrate for the synthesis of many biological compounds through the serotonin and kynurenine pathways. These compounds have a significant influence on gastrointestinal functions and mental processes. The aim of the study was to evaluate the urinary excretion of selected tryptophan metabolites in patients with constipation-predominant and diarrhoea-predominant irritable bowel syndrome (IBS-C and IBS-D, respectively), related to somatic and mental symptoms. (2) Methods: 120 people were included in the study and three groups were distinguished, with 40 individuals each, including healthy subjects (controls), patients with IBS-C and patients with IBS-D. The Gastrointestinal Symptoms Rating Scale (GSRS-IBS) was used to assess the severity of abdominal symptoms. The Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) were used to evaluate the mental state of patients. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), L-tryptophan and the following metabolites in urine, related to the creatinine level, were measured: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA). (3) Results: In both groups of patients with IBS, changes in tryptophan metabolism were found as compared to the control group. We observed an increase in the activity of the serotonin pathway and a positive correlation between the 5-HIAA level and the GSRS score (p &lt; 0.01) and HAM-A score (p &lt; 0.001) in IBS-D patients. The IBS-C group was characterized by a higher concentration of kynurenines (KYN, QA) in urine. Moreover, the QA (p &lt; 0.001) and KYNA (p &lt; 0.05) levels were correlated with the HAM-D score among IBS-C patients. (4) Conclusions: Various changes in the tryptophan metabolism pathway can determine the differences in the clinical picture of irritable bowel syndrome. These results should be included in the nutritional and pharmacological treatment of this syndrome