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Fulltext Bisphenol A, Dichlorodiphenyltrichloroethane (DDT) and Vinclozolin Affect ex-vivo Uterine Contraction in Rats via Uterotonin (Prostaglandin F2α, Acetylcholine and Oxytocin) Related Pathways

Salleh N, Giribabu N, Feng AO, Myint K

Int J Med Sci, 2015;12(11):914-25.
PMID: 26640411 DOI: 10.7150/ijms.11957

Bisphenol-A (BPA), dichrolodiphenyltrichloroethane (DDT) and vinclozolin were found able to induce abnormal uterine contraction. The mechanisms involved remains unclear. We hypothesized that the effect of these compounds were mediated via the uterotonin pathways. Therefore, in this study, effects of BPA, vinclozolin and DDT-only and in combination with uterotonins (PGF-2α, acetylcholine and oxytocin) on the force and pattern of uterine contraction were observed.
Changes in fluid composition and expression of ion channels in rat cervix during different phases of the estrus cycle

Salleh N, Ismail N, Nelli G, Myint K, Khaing SL

Biotech Histochem, 2022 Jan;97(1):53-66.
PMID: 33827344 DOI: 10.1080/10520295.2021.1899285

We investigated changes in the composition of cervical fluid at different phases of the female rat reproductive cycle. Fluid was collected from the cervix of rats by direct cervical flushing and analyzed for changes in Na+ and Cl- content and osmolarity. Following sacrifice, the cervix was harvested and expressions of mRNA and protein for ENaCs, CFTR and AQPs were measured using qPCR and immunohistochemistry, respectively. Cervical fluid Na+ and Cl- content was high during estrus, but osmolarity was high during metestrus and diestrus. Expressions of CFTR, AQP-1 and AQP-2 in the cervix were high during estrus, but low during diestrus. Expression of ENaC (α, β, γ), AQP-5 and AQP-7 was high during metestrus and diestrus and low during estrus. Changes in expression of ion channels in the cervix could explain changes in cervical fluid composition during the estrus cycle phases that could affect female fertility.
Cervical fluid pH, electrolytes and osmolarity changes and expression of ion transporters (ENaC, CFTR and AQP) in cervix of women with primary unexplained infertility

Ismail N, Myint K, Khaing SL, Giribabu N, Salleh N

Mol Biol Rep, 2023 Aug;50(8):6729-6737.
PMID: 37382776 DOI: 10.1007/s11033-023-08555-6

BACKGROUND: Unexplained infertility could arise from a defect in the cervix. However, the contribution of abnormal cervical fluid microenvironment to this problem still needs to be identified. Therefore, this study identifies the changes in the cervical fluid microenvironment, i.e., pH, electrolytes and osmolarity as well as expression of ion transporters in the cervix including ENaC, CFTR and AQP in fertile women and in women suffering from primary unexplained infertility.
METHODS: Fertile women and women with unexplained infertility but having regular 28-day menstrual cycles were chosen in this study, Day-22 serum progesterone levels were determined. In the meantime, serum FSH and LH levels were determined on day 2 while, cervical flushing was performed at day 14 to analyse changes in the cervical fluid pH, osmolarity, Na+ and Cl- levels. Meanwhile, cells retrieved from cervical fluid were subjected to mRNA expression and protein distribution analysis for CFTR, AQP and ENaC by qPCR and immunofluorescence, respectively.
RESULTS: No significant changes in serum progesterone, FSH and LH levels were observed between the two groups. However, cervical fluid pH, osmolarity, Na+ and Cl- levels were significantly lower in primary unexplained infertile group when compared to fertile group. Expression of CFTR and AQP (AQP 1, AQP 2, AQP 5 and AQP 7) in endocervical cells was lower and expression of β-ENaC was higher in primary unexplained infertile women (p
Dental Students' Educational Environment and Perceived Stress: The University of Malaya Experience

Myint K, See-Ziau H, Husain R, Ismail R

Malays J Med Sci, 2016 May;23(3):49-56.
PMID: 27418869

An equitable and positive learning environment fosters deep self-directed learning in students and, consequently, good practice in their profession. Although demotivating weaknesses may lead to repeated day-to-day stress with a cascade of deleterious consequences at both personal and professional levels, a possible relationship between these parameters has not been reported. This study was undertaken to determine the relationship between students' perceptions of their educational environment and their stress levels.
Fulltext Effects of stress associated with academic examination on the kynurenine pathway profile in healthy students

Myint K, Jacobs K, Myint AM, Lam SK, Henden L, Hoe SZ, et al.

PLoS One, 2021;16(6):e0252668.
PMID: 34081742 DOI: 10.1371/journal.pone.0252668

The effects of stress on the neuroendocrine, central nervous and immune systems are extremely complex. The kynurenine pathway (KP) of the tryptophan metabolism is recognised as a cross-link between the neuroendocrine- and immune systems. However, the effects of acute stress from everyday life on KP activation have not yet been studied. This study aims to investigate changes in the levels of the KP neuroactive metabolites and cytokines in response to stress triggered by academic examinations. Ninety-two healthy first year medical students benevolently participated in the study. Parameters were measured pre- examination, which is considered to be a high-stress period, and post-examination, as a low-stress period. Stress induced by academic examinations significantly increases the perceived stress scores (p<0.001), serum cortisol levels (p<0.001) and brain-derived neurotrophic factor (BDNF) levels (p<0.01). It decreased IL-10 levels (p<0.05) but had no effect on IL-6 and TNF-alpha levels. Only the KP neuroactive metabolite, 3-hydroxykynurenine (3-HK) significantly increased (p<0.01) in the post-examination period. In addition, the stress scores positively correlated with the levels of cortisol (r2 = 0.297, p<0.01) at post examination. Acute stress triggered by academic examinations increases cortisol and BDNF production and suppresses the anti-inflammatory cytokine, IL-10, but did not increase significantly the levels of other pro-inflammatory cytokines, tryptophan, kynurenine and downstream KP metabolites. The concomitant increased levels of BDNF under the duress of acute examination stress appear to limit the levels pro-inflammatory markers, which may attenuate the action of cortisol and the neuroinflammatory branch of the KP.
Fulltext Psychological Stresses in Children Trigger Cytokine- and Kynurenine Metabolite-Mediated Abdominal Pain and Proinflammatory Changes

Myint K, Jacobs K, Myint AM, Lam SK, Lim YA, Boey CC, et al.

Front Immunol, 2021;12:702301.
PMID: 34539633 DOI: 10.3389/fimmu.2021.702301

Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography. Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p<0.05, but lower concentrations of IL-10, p<0.001, IL-6, p<0.001 and brain-derived neurotrophic factors (BDNF) p<0.01. In addition, a significant increase in the metabolite of the kynurenine pathway, 3-hydroxyanthranilic acid (3-HAA) p<0.01, a significant decrease in the concentrations of anthranilic acid (AA) p<0.001, together with an increased ratio of serum 3-HAA to AA (3-HAA/AA) p<0.001, was found in this cohort. These findings indicate the significant activation of the immune system and presence of inflammation in children with RAP than those with subclinical parasitic infections. Moreover, children with RAP tested with the Strengths and Difficulties Questionnaire (SDQ), displayed high psychological problems though these SDQ scores were not statistically associated with measured cytokines and kynurenine metabolites. We however could hypothesize that the pro-inflammatory state together with concomitant low concentrations of BDNF in those children with RAP could play a role in psychological stress and experiencing medically unexplained symptoms.
Fulltext Escalating progression of mental health disorders during the COVID-19 pandemic: Evidence from a nationwide survey

Wong LP, Alias H, Md Fuzi AA, Omar IS, Mohamad Nor A, Tan MP, et al.

PLoS One, 2021;16(3):e0248916.
PMID: 33765039 DOI: 10.1371/journal.pone.0248916

Since the first nationwide movement control order was implemented on 18 March 2020 in Malaysia to contain the coronavirus disease 2019 (COVID-19) outbreak, to what extent the uncertainty and continuous containment measures have imposed psychological burdens on the population is unknown. This study aimed to measure the level of mental health of the Malaysian public approximately 2 months after the pandemic's onset. Between 12 May and 5 September 2020, an anonymous online survey was conducted. The target group included all members of the Malaysian population aged 18 years and above. The Depression Anxiety Stress Scale (DASS-21) was used to assess mental health. There were increased depressive, anxiety and stress symptoms throughout the study period, with the depression rates showing the greatest increase. During the end of the data collection period (4 August-5 September 2020), there were high percentages of reported depressive (59.2%) and anxiety (55.1%) symptoms compared with stress (30.6%) symptoms. Perceived health status was the strongest significant predictor for depressive and anxiety symptoms. Individuals with a poorer health perception had higher odds of developing depression (odds ratio [OR] = 5.68; 95% confidence interval [CI] 3.81-8.47) and anxiety (OR = 3.50; 95%CI 2.37-5.17) compared with those with a higher health perception. By demographics, young people-particularly students, females and people with poor financial conditions-were more vulnerable to mental health symptoms. These findings provide an urgent call for increased attention to detect and provide intervention strategies to combat the increasing rate of mental health problems in the ongoing COVID-19 pandemic.