Higher Serotonin Levels Research Articles

Night shift work and altered metabolic profile among hospital female nurses: results from a targeted metabolomic approach

BACKGROUND AND AIM: Shift work, especially including night shift (NSW), has been found associated with several diseases, including obesity, diabetes, cancers, and cardiovascular, mental, gastrointestinal and sleep disorders. Metabolomics (an omics-based methodology) may shed light on the mechanisms underlying these associations, which are not yet fully understood. We thus aimed to evaluate the effect of NSW on serum metabolites in a sample of hospital female nurses. METHODS: We recruited 46 nurses currently working in NSW in Milan (Italy), matched to 51 colleagues not employed in night shifts. Participants filled in a questionnaire on demographics, lifestyle habits, personal and family health history and work, and donated a blood sample. The metabolome was evaluated through a validated targeted approach measuring 188 metabolites. Only metabolites with at least 50% observations above the detection limit were considered, after standardization and log-transformation. Associations between each metabolite and NSW were assessed applying Tobit regression models and Random Forest, a machine-learning algorithm. RESULTS: When comparing current vs. never night shifters, we observed lower levels of 21 glycerophospholipids and 6 sphingolipids, and higher levels of serotonin (+171.0%, 95%CI: 49.1-392.7), aspartic acid (+155.8%, 95%CI: 40.8-364.7), and taurine (+182.1%, 95%CI: 67.6-374.9). The latter was higher in former vs. never night shifters too (+208.8%, 95%CI: 69.2-463.3). Tobit regression comparing ever (i.e., current + former) and never night shifters returned similar results. Years worked in night shifts did not seem to affect metabolite levels. The Random-Forest algorithm confirmed taurine and aspartic acid among the most important variables in discriminating current vs. never night shifters. CONCLUSIONS: This study, although based on a small sample size, shows altered levels of some metabolites in night shift workers. If confirmed, our results may shed light on the mechanisms potentially underlying the association between NSW and several pathologic states. KEYWORDS: night shift work, targeted metabolomics, machine learning

Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization

Macrophages (MФ) are an essential immune cell for defense and repair that travel to different tissues and adapt based on local stimuli. A critical factor that may govern their polarization is the crosstalk between metabolism and epigenetics. However, simultaneous measurements of metabolites, epigenetics, and proteins (phenotype) have been a major technical challenge. To address this, we have developed a novel triomics approach using mass spectrometry to comprehensively analyze metabolites, proteins, and histone modifications in a single sample. To demonstrate this technique, we investigated the metabolic-epigenetic-phenotype axis following polarization of human blood–derived monocytes into either ‘proinflammatory M1-’ or ‘anti-inflammatory M2-’ MФs. We report here a complex relationship between arginine, tryptophan, glucose, and the citric acid cycle metabolism, protein and histone post-translational modifications, and human macrophage polarization that was previously not described. Surprisingly, M1-MФs had globally reduced histone acetylation levels but high levels of acetylated amino acids. This suggests acetyl-CoA was diverted, in part, toward acetylated amino acids. Consistent with this, stable isotope tracing of glucose revealed reduced usage of acetyl-CoA for histone acetylation in M1-MФs. Furthermore, isotope tracing also revealed MФs uncoupled glycolysis from the tricarboxylic acid cycle, as evidenced by poor isotope enrichment of succinate. M2-MФs had high levels of kynurenine and serotonin, which are reported to have immune-suppressive effects. Kynurenine is upstream of de novo NAD+ metabolism that is a necessary cofactor for Sirtuin-type histone deacetylases. Taken together, we demonstrate a complex interplay between metabolism and epigenetics that may ultimately influence cell phenotype.

Positive Effects of α-Lactalbumin in the Management of Symptoms of Polycystic Ovary Syndrome.

To date, the involvement of α-Lactalbumin (α-LA) in the management of polycystic ovary syndrome (PCOS) refers to its ability to improve intestinal absorption of natural molecules like inositols, overcoming the inositol resistance. However, due to its own aminoacidic building blocks, α-LA is involved in various biological processes that can open new additional applications. A great portion of women with PCOS exhibit gastrointestinal dysbiosis, which is in turn one of the triggering mechanisms of the syndrome. Due to its prebiotic effect, α-LA can recover dysbiosis, also improving the insulin resistance, obesity and intestinal inflammation frequently associated with PCOS. Further observations suggest that altered gut microbiota negatively influence mental wellbeing. Depressive mood and low serotonin levels are indeed common features of women with PCOS. Thanks to its content of tryptophan, which is the precursor of serotonin, and considering the strict link between gut and brain, using α-LA contributes to preserving mental well-being by maintaining high levels of serotonin. In addition, considering women with PCOS seeking pregnancy, both altered microbiota and serotonin levels can induce later consequences in the offspring. Therefore, a deeper knowledge of potential applications of α-LA is required to transition to preclinical and clinical studies extending its therapeutic advantages in PCOS.

Antidepressive-like Behavior-Related Metabolomic Signatures of Sigma-1 Receptor Knockout Mice

Sigma-1 receptor (Sig1R) has been proposed as a therapeutic target for neurological, neurodegenerative, and psychiatric disorders, including depression and anxiety. Identifying metabolites that are affected by Sig1R absence and cross-referencing them with specific mood-related behaviors would be helpful for the development of new therapies for Sig1R-associated disorders. Here, we examined metabolic profiles in the blood and brains of male CD-1 background Sig1R knockout (KO) mice in adulthood and old age and correlated them with the assessment of depression- and anxiety-related behaviors. The most pronounced changes in the metabolic profile were observed in the plasma of adult Sig1R KO mice. In adult mice, the absence of Sig1R significantly influenced the amino acid, sphingolipid (sphingomyelin and ceramide (18:1)), and serotonin metabolic pathways. There were higher serotonin levels in plasma and brain tissue and higher histamine levels in the plasma of Sig1R KO mice than in their age-matched wild-type counterparts. This increase correlated with the reduced behavioral despair in the tail suspension test and lack of anhedonia in the sucrose preference test. Overall, these results suggest that Sig1R regulates behavior by altering serotonergic and histaminergic systems and the sphingolipid metabolic pathway.

European Neuroendocrine Tumor Society (ENETS) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease

European Neuroendocrine Tumor Society (<scp>ENETS</scp>) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease

Activation of Estrogen Receptor β in the Lateral Habenula Improves Ovariectomy-Induced Anxiety-Like Behavior in Rats.

BackgroundLoss of estrogen due to menopause or ovarian resection is involved in the development of anxiety, which negatively impacts work productivity and quality of life. Estrogen modulates mood by binding to estrogen receptors in the brain. Estrogen receptor beta (ERβ) is highly expressed in the lateral habenula (LHb), a key site for controlling the activities of dopaminergic neurons in the ventral tegmental area (VTA) and serotoninergic neurons in the dorsal raphe nucleus (DRN) that are known to be involved in anxiety.MethodsIn this study, we examined the role of LHb in the anxiolytic-like effect of estrogen in ovariectomized (OVX) rats. The establishment of OVX anxiety model was validated in behavioral tests, including elevated plus maze (EPM) and mirror chamber maze (MCM) tasks. The expression of c-Fos in the LHb neurons was analyzed by immunohistochemistry, and monoamine neurotransmitter levels in related nuclei were analyzed using high-performance liquid chromatography (HPLC).ResultsEstrogen-treated OVX rats showed a lower degree of anxiety-like behavior than OVX rats. OVX rats showed anxiety-like behavior and low monoamine levels in the DRN and VTA compared with sham operated and estrogen-treated OVX rats. c-Fos expression in the LHb was higher than that in the sham operated and estrogen-treated OVX rats. Intra-LHb injection of the ERβ-selective agonist diarylprepionitrile (DPN) reduced expression of c-Fos (a neuronal activity marker) and anxiety-like behavior in OVX rats, but not in normal rats, as evidenced by increased time spent in EPM open areas and the MCM mirror chamber. These changes coincided with higher levels of serotonin and dopamine in the DRN and higher dopamine levels in the VTA in OVX rats receiving intra-LHb DPN compared with those receiving vehicle injection.ConclusionThese results suggest that OVX-induced anxiety-like behavior may be associated with increased LHb activity. DPN may inhibit LHb activity to improve anxiety-like behavior in OVX rats by increasing monoamine neurotransmitter levels in the DRN and VTA.

Probiotics: Facts and Myths

Probiotics square measure live microorganisms that, once administered in adequate amounts, confer a health profit on the host (FAO, 2014). Bifidobacterium and strains of carboxylic acid microorganism square measure the foremost wide used microorganism that exhibit prebiotic properties and square measure enclosed in several practical foods and dietary supplements (Diaz et al. 2019). The gut is a glorious place responsible for our digestive health and our overall well-being, including our mental health. A good gut leads to a strong immune system, less stress, and even higher serotonin levels (Leghari et al., 2021). According to scientific research, specific strains of probiotic microbes impart health advantages to the host and are safe for human consumption. However, because these effects are strain-specific, this information cannot be generalized to other strains. Probiotics may provide health advantages for problems like gastrointestinal infections, genitourinary infections, allergies, and some bowel disorders, which affect a large section of the world's population (Daliri et al., 2019). Increased awareness and knowledge of gut-healthy foods and the availability of a variety of gut-healthy foods at all levels of Indian society can improve overall health and avoid chronic diseases.

Effect of Angiotensin Receptor Blocker and Probiotics in Caffeine-Induced Anxiety Model

Aim: To evaluate to anti-anxiety effectof probiotics and angiotensine receptor blocker in caffeine induced anxiety rat model.&#x0D; Methodology: The study was conducted in six groups (n=6). Caffeine was given intraperitoneally at a dosage of 25 mg/kg each day for 14 days. Blood samples, body temperature, and glucose measurements were taken prior to the trial. Caffeine was given intraperitoneally to G1-G5 mice at a dosage of 25 mg/kg. For groups 3 and 4, a probiotic formulation was given orally following the caffeine dosage. In group 5, a probiotic topical gel (30 mg) was given topically to the animals' foreheads. Diazepam (1 mg/kg) was given to group 2 animals.&#x0D; Results: The body weight was not changed significantly throughout the study period in all the groups. Mortality and clinical signs were not observed during study. When compared to the anxiety control group, there was no statistical significance in either of the groups' glucose levels. There was no statistical significance in Hemoglobin (Hb) levels of animals on day 14 when we compare with anxiety control group. The changes in SGOT and SGPT levels were not found to be statistically significant. There was no statistical significance in rectal temperature of animals. There was no statistical significance in all the groups in hot plate readings on day 7 when compared with anxiety control group. Whereas there was significance increase in latency time (time spent) was observed in group 2 &amp; group 6 when compared to anxiety control group on day 14. Probiotic high dosage and probiotic topic gel treated animals similarly spent significantly more time in open arms than anxiety control animals (P&lt; 0.01). High serotonin levels were observed In the anxiety control rats .however it reduced in treatment groups.&#x0D; Conclusion: The study concludes the potential benefit of probiotics and Losartan for the treatment of caffeine induced anxiety.

Features and patterns of changes in neurochemical parameters at different stages of chronic mercury intoxication

Introduction. At present, the features of the clinical picture and pathogenesis of the formation and progression of chronic intoxication under the influence of mercury remain insufficiently studied. Purpose. To study the features and patterns of changes in the neurotransmitters and neurotrophic factors concentration at different stages of chronic mercury intoxication (CMI). Materials and methods. A cohort examination of 69 workers (group 1) exposed to mercury, 18 individuals in the initial period of CMI (group 2), and 55 patients in the long-term period (group 3) were carried out. The content of neurotransmitters and neurotrophic factors was determined by enzyme immunoassay. The statistical processing included Wilcoxon, Kruskal-Wallis and Mann-Whitney tests. Results. Higher levels of histamine were found in group 2, low levels of metanephrine in group 1, and normetanephrine in group 3. An increase in the BDNF concentration was revealed in group 2 compared with groups 1 and 3. The content of neurotrophin-3 in group 3 was statistically significantly lower than in group 2. Conclusion. The general pattern for all stages is an increase in the norepinephrine and CNTF concentration. Mercury neurointoxication at all stages is characterized by high serotonin levels. A distinctive feature for trained workers is a compensatory increase in the normetanephrine level and a low BDNF and NT-3. For the initial period of CMI, an increase in the histamine, BDNF and NT-3 content is characteristic. The long-term period is characterized by an imbalance in the concentration of the studied neurotransmitters and neurotrophic factors.

Post-Stroke Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Attenuates Chronic Changes in Brain Metabolism, Increases Neurotransmitter Levels, and Improves Recovery.

The aim of this study was to test whether poststroke oral administration of a small molecule p75 neurotrophin receptor (p75NTR) modulator (LM11A-31) can augment neuronal survival and improve recovery in a mouse model of stroke. Mice were administered LM11A-31 for up to 12 weeks, beginning 1 week after stroke. Metabolomic analysis revealed that after 2 weeks of daily treatment, mice that received LM11A-31 were distinct from vehicle-treated mice by principal component analysis and had higher levels of serotonin, acetylcholine, and dopamine in their ipsilateral hemisphere. LM11A-31 treatment also improved redox homeostasis by restoring reduced glutathione. It also offset a stroke-induced reduction in glycolysis by increasing acetyl-CoA. There was no effect on cytokine levels in the infarct. At 13 weeks after stroke, adaptive immune cell infiltration in the infarct was unchanged in LM11A-31-treated mice, indicating that LM11A-31 does not alter the chronic inflammatory response to stroke at the site of the infarct. However, LM11A-31-treated mice had less brain atrophy, neurodegeneration, tau pathology, and microglial activation in other regions of the ipsilateral hemisphere. These findings correlated with improved recovery of motor function on a ladder test, improved sensorimotor and cognitive abilities on a nest construction test, and less impulsivity in an open field test. These data support small molecule modulation of the p75NTR for preserving neuronal health and function during stroke recovery. SIGNIFICANCE STATEMENT: The findings from this study introduce the p75 neurotrophin receptor as a novel small molecule target for promotion of stroke recovery. Given that LM11A-31 is in clinical trials as a potential therapy for Alzheimer's disease, it could be considered as a candidate for assessment in stroke or vascular dementia studies.

Weight Loss Outcomes Among Early High Responders to Exenatide Treatment: A Randomized, Placebo Controlled Study in Overweight and Obese Women.

ObjectiveAs there is significant heterogeneity in the weight loss response to pharmacotherapy, one of the most important clinical questions in obesity medicine is how to predict an individual’s response to pharmacotherapy. The present study examines patterns of weight loss among overweight and obese women who demonstrated early robust response to twice daily exenatide treatment compared to those treated with hypocaloric diet and matched placebo injections.MethodsWe randomized 182 women (BMI 25-48 kg/m2) to treatment with exenatide alone or matched placebo injections plus hypocaloric diet. In both treatment groups, women who demonstrated ≥ 5% weight loss at 12 weeks were characterized as high responders and those who lost ≥10% of body weight were classified as super responders. Our primary outcome was long-term change in body weight among early high responders to either treatment. An exploratory metabolomic analysis was also performed.ResultsWe observed individual variability in weight loss with both exenatide and hypocaloric diet plus placebo injections. There was a trend toward a higher percentage of subjects who achieved ≥ 5% weight loss with exenatide compared to diet (56% of those treated with exenatide, 76% of those treated with diet, p = 0.05) but no significant difference in those who achieved ≥ 10% weight loss (23% of individuals treated with exenatide and 36% of those treated with diet, p = 0.55). In both treatment groups, higher weight loss at 3 months of treatment predicted super responder status (diet p=0.0098, exenatide p=0.0080). Both treatment groups also demonstrated similar peak weight loss during the study period. We observed lower cysteine concentrations in the exenatide responder group (0.81 vs 0.48 p < 0.0001) and a trend toward higher levels of serotonin, aminoisobutyric acid, anandamide, and sarcosine in the exenatide super responder group.ConclusionIn a population of early high responders, longer term weight loss with exenatide treatment is similar to that achieved with a hypocaloric diet.Clinical Trial Registration www.clinicaltrialsgov, identifier NCT01590433.

Characterization of Skeletal Phenotype and Associated Mechanisms With Chronic Intestinal Inflammation in theWinnieMouse Model of Spontaneous Chronic Colitis

Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, studies have been scarce, mainly because of the lack of an appropriate animal model of colitis-associated bone loss. In this study, we aimed to decipher skeletal manifestations in the Winnie mouse model of spontaneous chronic colitis, which carries a MUC2 gene mutation and closely replicates ulcerative colitis. In our study, Winnie mice, prior to the colitis onset at 6 weeks old and progression at 14 and 24 weeks old, were compared with age-matched C57BL/6 controls. We studied several possible mechanisms involved in colitis-associated bone loss. We assessed for bone quality (eg, microcomputed tomography [micro-CT], static and dynamic histomorphometry, 3-point bending, and ex vivo bone marrow analysis) and associated mechanisms (eg, electrochemical recordings for gut-derived serotonin levels, real-time polymerase chain reaction [qRT-PCR], double immunofluorescence microscopy, intestinal inflammation levels by lipocalin-2 assay, serum levels of calcium, phosphorus, and vitamin D) from Winnie (6-24 weeks) and age-matched C57BL6 mice. Deterioration in trabecular and cortical bone microarchitecture, reductions in bone formation, mineral apposition rate, bone volume/total volume, osteoid volume/bone surface, and bone strength were observed in Winnie mice compared with controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice compared with controls. Upregulation of 5-HTR1B gene and increased association of FOXO1 with ATF4 complex were identified as associated mechanisms concomitant to overt inflammation and high levels of gut-derived serotonin in 14-week and 24-week Winnie mice. Skeletal phenotype of the Winnie mouse model of spontaneous chronic colitis closely represents manifestations of IBD-associated osteoporosis/osteopenia. The onset and progression of intestinal inflammation are associated with increased gut-derived serotonin level, increased bone resorption, and decreased bone formation.

Parental selection for growth and early-life low stocking density increase the female-to-male ratio in European sea bass

In European sea bass (Dicentrarchus labrax), as in many other fish species, temperature is known to influence the sex of individuals, with more males produced at relatively high temperatures. It is however unclear to what extent growth or stress are involved in such a process, since temperature is known to influence both growth rate and cortisol production. Here, we designed an experiment aiming at reducing stress and affecting early growth rate. We exposed larvae and juveniles originating from both captive and wild parents to three different treatments: low stocking density, food supplemented with tryptophan and a control. Low stocking density and tryptophan treatment respectively increased and decreased early growth rate. Each treatment influenced the stress response depending on the developmental stage, although no clear pattern regarding the whole-body cortisol concentration was found. During sex differentiation, fish in the low-density treatment exhibited lower expression of gr1, gr2, mr, and crf in the hypothalamus when compared to the control group. Fish fed tryptophan displayed lower crf in the hypothalamus and higher level of serotonin in the telencephalon compared to controls. Overall, fish kept at low density produced significantly more females than both control and fish fed tryptophan. Parents that have been selected for growth for three generations also produced significantly more females than parents of wild origin. Our findings did not allow to detect a clear effect of stress at the group level and rather point out a key role of early sexually dimorphic growth rate in sex determination.

Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study.

Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated.

Sex-dependent changes in the microbiota profile, serum metabolism, and hormone levels of growing pigs after dietary supplementation with Lactobacillus.

Dietary supplementation with Lactobacillus can improve the intestinal microbial balance and exerts beneficial effects on pig health. However, whether these effects in pigs show differences between the sexes remains poorly understood. Therefore, we analyzed the sex-dependent patterns in the fecal microbiota after dietary supplementation with Lactobacillus acidophilus ZLA012 through high-throughput sequencing, determined the metabolomic profile of serum in barrows (immature castrated males) and gilts (sexually immature females) through nontargeted liquid chromatography-mass spectrometry, and measured the levels of various hormones, such as insulin, growth hormone, serotonin, triiodothyronine, and thyroxine. Lactobacillus supplementation resulted in more obvious effects on the microbial diversity and composition in barrows than in gilts. Specifically, supplementation with L. acidophilus ZLA012 significantly increased the abundance of the phylum Bacteroidetes and decreased that of Firmicutes in barrows. In contrast, more notable effects on metabolites, particularly those involved in lipid metabolism and glycerophospholipid metabolism, were observed in gilts than in barrows after Lactobacillus supplementation. Megasphaera, Dialister, Gemmiger, Faecalibacterium, Bulleidia, and Prevotella were the core functional genera associated with the significantly affected metabolites, which are involved in the biosynthesis, degradation, and elongation of fatty acids. L. acidophilus ZLA012 treatment increased the serum insulin, total bile acid, lipoprotein lipase, and nicotinamide adenine dinucleotide (NAD)+ levels in gilts, whereas higher serotonin levels were found in barrows than in gilts. The results indicated that the separate housing of barrows and gilts might be beneficial for targeted dietary supplementation and application of Lactobacillus in pig production. KEY POINTS: • L. acidophilus exerted obvious effects on microbiota profiles for barrows than gilts. • Gilts treated by L. acidophilus had a greater variety of lipid metabolism compared with barrows. • Lactobacillus regulated the dynamic balance among the microbiota, metabolism, and hormone in pigs.

Serotonin-Its Synthesis and Roles in the Healthy and the Critically Ill.

Serotonin (5-hydroxytryptamine, 5-HT) plays two important roles in humans—one central and the other peripheral—depending on the location of the 5-HT pools of on either side of the blood-brain barrier. In the central nervous system it acts as a neurotransmitter, controlling such brain functions as autonomic neural activity, stress response, body temperature, sleep, mood and appetite. This role is very important in intensive care, as in critically ill patients multiple serotoninergic agents like opioids, antiemetics and antidepressants are frequently used. High serotonin levels lead to altered mental status, deliria, rigidity and myoclonus, together recognized as serotonin syndrome. In its role as a peripheral hormone, serotonin is unique in controlling the functions of several organs. In the gastrointestinal tract it is important for regulating motor and secretory functions. Apart from intestinal motility, energy metabolism is regulated by both central and peripheral serotonin signaling. It also has fundamental effects on hemostasis, vascular tone, heart rate, respiratory drive, cell growth and immunity. Serotonin regulates almost all immune cells in response to inflammation, following the activation of platelets.

The effect of tryptophan and serotonin levels on the severity of depressive and climacteric symptoms in perimenopausal women.

The dysfunctional serotonergic system is a factor contributing to the development of depression. The aim of this study was to assess the effect of serotonin and tryptophan on the severity of climacteric and depressive symptoms in perimenopausal women. The study involved data collection and biochemical analysis. The research instruments were: the Blatt-Kuppermann index, the Beck Depression Inventory, and the proprietary questionnaire. There was no significant effect of tryptophan (r=0.05; p=0.219) and serotonin (r= -0.03; p=0.537) on the severity of depressive symptoms, or tryptophan on the severity of climacteric symptoms (r=0.019; p=0.657). However, a weak negative correlation was found between the level of serotonin and the severity of climacteric symptoms (r=-0.09; p=0.022). Additionally, it was found that severe depressive symptoms were associated with a significant exacerbation of climacteric symptoms (β=0.379; p<0.001), while higher serotonin levels alleviated them (β=-0.604; p=0.005). Higher severity of depressive symptoms may exacerbate climacteric symptoms. Serotonin levels may influence the severity of climacteric symptoms. Moreover, the higher the serotonin level, the lower the odds of depressive disorders, irrespective of the severity of climacteric symptoms. Tryptophan levels had no effect on the severity of depressive and climacteric symptoms in the perimenopausal women.

Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus.

Background/AimsThe pathogenesis of gastrointestinal (GI) symptoms in patients with type 2 diabetes mellitus (T2DM) is yet to be delineated clearly. Serotonin, a monoamine neurotransmitter, resides primarily in the gut and plays a vital role in GI system. However, no study has been documented the role of serotonin and serotonin transporter gene (SLC6A4) polymorphism in the development of GI symptoms in T2DM patients.MethodsThree hundred diabetes patients attending diabetes clinic at Postgraduate Institute of Medical Education and Research, Chandigarh, and matched healthy controls were enrolled for this study. Plasma from collected blood sample was used for serotonin measurement by enzyme-linked immunosorbent assay method and buffy coat was used for isolation of DNA by phenol chloroform method. Serotonin transporter gene polymorphism was analyzed by polymerase chain reaction method.ResultsThe frequency of short allele (S) and SS genotype was significantly higher in patients with T2DM than controls and was associated with increased risk of T2DM. The frequency of LS genotype showed an association with protection from the disease. Regarding GI symptoms, 78.2% of patients with constipation showed LL and LS genotypes, and 97.7% of patients with diarrhea had SS genotype. The patients without GI symptoms did not show any association of gut motility with genotype. Furthermore, serotonin was significantly higher in diabetic patients who belonged to SS genotype compared to LS or LL genotype and who presented with diarrhea.ConclusionSS genotypes are prone to develop diarrhea because of faster gut motility resulting from higher serotonin levels as compared to LS and LL genotype in T2DM patients.

Right and Left-sided Valve Disease: A Case of Subclinical Intrapulmonary Shunt in an Adult with Malignant Carcinoid

Carcinoid tumors are highly differentiated neuroendocrine tumors (NET) that most commonly originate from the gastrointestinal tract. Liver metastases bypass first-pass metabolism and liberate vasoactive hormones into systemic circulation, causing flushing and diarrhea. Prolonged levels of circulating serotonin may adversely affect the heart by creating fibrotic endocardial deposits on native valves. The remaining serotonin is metabolized in the pulmonary circuit that leads to pathognomonic valvular disease isolated to the right side of the heart. We present a case of an adult male with known carcinoid syndrome who presented with involvement of right, as well as left-sided valves. He was found to have an intrapulmonary shunt on transesophageal echocardiogram (TEE) with bubble study. Intrapulmonary shunt should be considered, in conjunction with right-to-left shunt, lung involvement, and high levels of serotonin, for carcinoid patients with right and left-sided valve disease.

Selection and Micropropagation of an Elite Melatonin Rich Tulsi (Ocimum sanctum L.) Germplasm Line

Tulsi (Ocimum sanctum L.) is a sacred plant of medicinal and spiritual significance in many cultures. Medicinal properties of Tulsi are ascribed to its phytochemicals with antioxidant capabilities. The current study was undertaken to screen a large seed population of Tulsi to select germplasm lines with high antioxidant potential and to standardize protocols for micropropagation and biomass production to produce a phytochemically consistent crop. A total of 80 germplasm lines were established under in vitro conditions and screened for their antioxidant potential determined with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) bioassay. The micropropagation of a selected line, named Vrinda, was established using nodal cultures grown on Murashige and Skoog medium containing benzylaminopurine (1.1 µM), gibberellic acid (0.3 µM), and activated charcoal (0.6%). The antioxidant phytohormones melatonin and serotonin were quantified in the field and greenhouse grown tissues of Vrinda and melatonin levels were found to be consistent in both conditions with higher serotonin levels under field conditions. This integrated approach combining the in vitro selection and propagation offers potential applications in the development of safe, effective, and novel natural health products of Tulsi, and many other medicinal plant species.