Displaying publications 801 - 819 of 819 in total

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  1. Shahrudin MD, Noori SM
    Hepatogastroenterology, 1997;44(14):441-4.
    PMID: 9164516
    BACKGROUND/AIMS: Recently an increasing number of young colorectal carcinoma patients attending the University Hospital, Kuala Lumpur were noted. This report represents our experience with patients suffering from colorectal cancer aged 30 years or younger.
    MATERIALS AND METHODS: All cases of primary carcinoma of the colon and rectum admitted to the University Hospital during 1990 to 1994 were respectively reviewed. Inclusion criteria was that the patient had been 30 years or younger. Data collected included age, gender, race, site of tumour, presenting symptomatology, duration of symptoms, histology, extension of tumour and nodal involvement predisposing factors, treatment and follow-up.
    RESULTS: 21 patients were included, 5 patients (24%) were 30 years old at diagnosis, 12 (57%) patients were aged 20-29 years and 4 patients (19%) were less than 20 years old. Thirteen of the 21 patients were female, and 8 (38%) were male, 6 of the 21 patients (29%) were Malaysian, while 1 was Indian (4%). The remainder were Chinese, 14 patients (67%). Six patients (29%) had their primary tumour located in the rectosigmoid, 4 (19%) in the left colon, 1 (4%) in the splenic flexure, 2 in the transverse colon (9%), 1 in the hepatic flexure (4%) and 5 in the caecum 24(%). One patient had a tumour too diffuse to detect a primary site at the time of operation. One patient with a family history of polyps had his entire colon removed at age 14. He had 3 separate foci of tumour. The 5-year survival rate was 25%.
    DISCUSSION: Most patients with extensive disease and mucinous histology. Lesions are commonly seen beyond the transverse colon (57%). Presentation included most commonly abdominal pain, haematochezia or haemoccult positive stools.
    CONCLUSION: The symptoms above should alert surgeons to colorectal carcinoma as a differential diagnosis
    Matched MeSH terms: Sex Factors
  2. Ramalingaswami V
    Ann Intern Med, 1973 Feb;78(2):277-83.
    PMID: 4265088
    Matched MeSH terms: Sex Factors
  3. Lee YS, Kek BL, Poh LK, Saw SM, Loke KY
    J Pediatr Gastroenterol Nutr, 2008 Aug;47(2):172-8.
    PMID: 18664869 DOI: 10.1097/MPG.0b013e318162a0e5
    To identify factors associated with raised alanine transaminase, aspartate transaminase, and gamma-glutaryl transferase in severely obese children
    Matched MeSH terms: Sex Factors
  4. Walker JD, Spiro G, Loewen K, Jacklin K
    J Alzheimers Dis, 2020;78(4):1439-1451.
    PMID: 33185601 DOI: 10.3233/JAD-200704
    BACKGROUND: There remains a lack of information and understanding of the prevalence and incidence of Alzheimer's disease and related dementia in Indigenous populations. Little evidence available suggests that Indigenous peoples may have disproportionately high rates of Alzheimer's disease and related dementia (ADRD).

    OBJECTIVE: Given this information, this study systematically explores what risk factors may be associated with ADRD in Indigenous populations.

    METHODS: A search of all published literature was conducted in October 2016, March 2018, and July 2019 using Medline, Embase, and PsychINFO. Subject headings explored were inclusive of all terms related to Indigenous persons, dementia, and risk. All relevant words, phrases, and combinations were used. To be included in this systematic review, articles had to display an association of a risk factor and ADRD. Only studies that reported a quantifiable measure of risk, involved human subjects, and were published in English were included.

    RESULTS: Of 237 articles originally identified through database searches, 45 were duplicates and 179 did not meet a priori inclusion criteria, resulting in 13 studies eligible for inclusion in this systematic review.

    CONCLUSION: The large number of potentially modifiable risk factors reported relative to non-modifiable risk factors illustrates the importance of socioeconomic context in the pathogenesis of ADRD in Indigenous populations. The tendency to prioritize genetic over social explanations when encountering disproportionately high disease rates in Indigenous populations can distract from modifiable proximal, intermediate, and distal determinants of health.

    Matched MeSH terms: Sex Factors
  5. Rafique G, Bukhsh A, Gul A, Khiljee S, Ashraf M, Omer MO
    Pak J Pharm Sci, 2017 Jan;30(1):11-16.
    PMID: 28603106
    180 million people are affected by chronic Hepatitis C Virus infection globally and more than 50 million in South East Asia. Combination of Interferon and Ribavirin is the current anti-HCV therapy in practice and is associated with certain hematologic adverse effects. In this concurrent observational study the incidence rate of major hematologic adverse effects and efficacy outcomes of Interferon and Ribavirin combination therapy was evaluated in 288 chronic hepatitis C patients at Lahore General Hospital. Levels of Hb, TLC, and Platelets counts were monitored for hematologic adverse effects monitoring, whereas, ALT, AST and bilirubin levels were monitored for efficacy. PCR was done at week 4, 12 &36 for therapeutic success evaluation. A significant reduction in Hb levels (p<0.05) was observed after week 4, 8 and 12 of therapy. Frequency of anemia increased in both genders with body weight <65kg and platelet count <150,000/mm(3). End Treatment Response (ETR) was achieved in 64.5%. Anemia was the major side effect of the combination therapy particularly in the males. Higher ETR was observed in patients who achieved RVR and were <50 years of age.
    Matched MeSH terms: Sex Factors
  6. Tan CH, Tan KY, Yap MK, Tan NH
    Sci Rep, 2017 02 27;7:43237.
    PMID: 28240232 DOI: 10.1038/srep43237
    Tropidolaemus wagleri (temple pit viper) is a medically important snake in Southeast Asia. It displays distinct sexual dimorphism and prey specificity, however its venomics and inter-sex venom variation have not been thoroughly investigated. Applying reverse-phase HPLC, we demonstrated that the venom profiles were not significantly affected by sex and geographical locality (Peninsular Malaya, insular Penang, insular Sumatra) of the snakes. Essentially, venoms of both sexes share comparable intravenous median lethal dose (LD50) (0.56-0.63 μg/g) and cause neurotoxic envenomation in mice. LCMS/MS identified six waglerin forms as the predominant lethal principles, comprising 38.2% of total venom proteins. Fourteen other toxin-protein families identified include phospholipase A2, serine proteinase, snaclec and metalloproteinase. In mice, HPLC fractions containing these proteins showed insignificant contribution to the overall venom lethality. Besides, the unique elution pattern of approximately 34.5% of non-lethal, low molecular mass proteins (3-5 kDa) on HPLC could be potential biomarker for this primitive crotalid species. Together, the study unveiled the venom proteome of T. wagleri that is atypical among many pit vipers as it comprises abundant neurotoxic peptides (waglerins) but little hemotoxic proteinases. The findings also revealed that the venom is relatively well conserved intraspecifically despite the drastic morphological differences between sexes.
    Matched MeSH terms: Sex Factors
  7. Eskin M, AlBuhairan F, Rezaeian M, Abdel-Khalek AM, Harlak H, El-Nayal M, et al.
    Psychiatr Q, 2019 03;90(1):229-248.
    PMID: 30498939 DOI: 10.1007/s11126-018-9613-4
    There is a scarcity of research on suicidal phenomena in the Muslim world. Therefore, this study aimed at investigating the self-reported prevalence of suicidal thoughts, attempts and motives in 12 Muslim countries. A total of 8417 (54.4% women) university students were surveyed by means of a self-report questionnaire. Overall, 22% of the participants reported suicidal ideation and 8.6% reported attempting suicide. The odds of suicidal thoughts were elevated in Azerbaijan, Indonesia and Saudi Arabia, while reduced ORs were recorded in Egypt, Jordan, Lebanon and Malaysia. While odds of suicide attempts were high in Azerbaijan, Palestine and Saudi Arabia reduced odds ratios (OR) were detected in Indonesia, Iran, Jordan, Lebanon, Malaysia and Tunisia. Taking drugs and using a sharp instrument were the two most frequently used methods to attempt suicide. Only 32.7% of attempts required medical attention. Escape motives were endorsed more than social motives by participants who attempted suicide. Suicidal behaviors were more frequent in women than in men. Compered to men, fewer attempts by women required medical attention. Moreover, our results show that making suicide illegal does not reduce the frequency of suicidal behavior. Results from this comparative study show that suicidal thoughts and attempts are frequent events in young adults in countries where religious scripture explicitly prohibit suicide and the frequencies of nonfatal suicidal behavior show large variation in nations adhering to the same religion.
    Matched MeSH terms: Sex Factors
  8. Ahmad N, Shah SA, Abdul Gafor AH, Abdul Murad NA, Kamaruddin MA, Abd Jalal N, et al.
    Diabet Med, 2020 11;37(11):1890-1901.
    PMID: 32012348 DOI: 10.1111/dme.14257
    AIM: To examine the possible gene-environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease.

    METHODS: A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses.

    RESULTS: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI).

    CONCLUSIONS: Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.

    Matched MeSH terms: Sex Factors
  9. Chew SC, Khor GL, Loh SP
    J Nutr Sci Vitaminol (Tokyo), 2011;57(2):150-5.
    PMID: 21697634 DOI: 10.3177/jnsv.57.150
    Folate is of prime interest among investigators in nutrition due to its multiple roles in maintaining health, especially in preventing neural tube defects and reducing the risk of cardiovascular diseases. We investigated the effect of dietary folate intake on blood folate, vitamin B(12), vitamin B(6), and homocysteine status. One hundred subjects consisting of Chinese and Malay subjects volunteered to participate in this cross-sectional study. Dietary folate intake was assessed by 24-h dietary recall and a food-frequency questionnaire (FFQ). Serum and red blood cell folate were analyzed using a microbiological assay, while serum vitamin B(12) was determined by electrochemiluminescence immunoassay (ECLIA), and high-performance liquid chromatography (HPLC) was used for the determination of serum vitamin B(6) and homocysteine. The mean folate intake, serum folate, RBC folate, serum vitamin B(12), and B(6), were higher in female subjects, with the exception of serum homocysteine. The Chinese tended to have higher folate intake, serum folate, RBC folate, and vitamin B(12). A positive association was found between folate intake and serum folate while a negative association was found between folate intake and serum homocysteine. Stepwise linear regression of serum folate showed a significant positive coefficient for folate intake whilst a significant negative coefficient was found for serum homocysteine when controlling for age, gender, and ethnicity. In conclusion, high dietary folate intake helps to increase serum folate and to lower the homocysteine levels.
    Matched MeSH terms: Sex Factors
  10. Peltzer K, Pengpid S, Sychareun V, Ferrer AJG, Low WY, Huu TN, et al.
    BMC Cardiovasc Disord, 2017 08 23;17(1):230.
    PMID: 28835205 DOI: 10.1186/s12872-017-0666-3
    BACKGROUND: Existing evidence suggests that the cardiovascular morbidities are increasing among pre-hypertensive individuals compared to normal. The aim of this study was to evaluate the prevalence of prehypertension, hypertension and to identify psychosocial risk factors for prehypertension among university students in Association of South East Asian Nation (ASEAN) countries.
    METHODS: Based on a cross-sectional survey, the total sample included 4649 undergraduate university students (females = 65.3%; mean age 20.5, SD = 2.9, age range of 18-30 years) from 7 ASEAN countries (Indonesia, Laos, Malaysia, Myanmar, Philippines, Thailand and Vietnam). Blood pressure, anthropometric, health behaviour and psychosocial variables were measured.
    RESULTS: Overall, 19.0% of the undergraduate university students across ASEAN countries had prehypertension, 6.7% hypertension and 74.2% were normotensives. There was country variation in prehypertension prevalence, ranging from 11.3% in Indonesia and 11.5% in Malaysia to above 18% in Laos, Myanmar and Thailand. In multivariate analysis, sociodemographic variables (male gender, living in an upper middle income country, and living on campus or off campus on their own), nutrition and weight variables (not being underweight and obese, having once or more times soft drinks in a day and never or rarely having chocolate or candy), heavy drinking and having depressive symptoms were associated with prehypertension.
    CONCLUSION: The study found a high prevalence of prehypertension in ASEAN university students. Several psychosocial risk factors including male gender, obesity, soft drinks consumption, heavy drinking and depression symptoms have been identified which can help in intervention programmes.
    Matched MeSH terms: Sex Factors
  11. Gao F, Lam CS, Yeo KK, Machin D, de Carvalho LP, Sim LL, et al.
    J Am Heart Assoc, 2016 10 06;5(10).
    PMID: 27792637
    BACKGROUND: We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort.

    METHODS AND RESULTS: For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22-101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age-adjusted hazard ratio [HR] 1.3, 95% CI 1.2-1.4) but a similar risk of noncardiovascular death (HR 0.9, 95% CI 0.8-1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (HR 1.4, 95% CI 1.2-1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (HR 3.4 [95% CI 1.9-6.0] versus HR 1.5 [95% CI 0.6-3.6] for Indian women). Compared with same-age Malay men, Malay women aged 22 to 49 years had a 2.5-fold (95% CI 1.6-3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the HR comparing cardiovascular death of Indian women and men decreased from 1.9 (95% CI 1.5-2.4) at 30 days to 0.9 (95% CI 0.5-1.6) at 10 years.

    CONCLUSION: Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.

    Matched MeSH terms: Sex Factors
  12. Chye JK, Lim CT
    Singapore Med J, 1999 Sep;40(9):565-70.
    PMID: 10628243
    To determine the survival rates and risk factors associated with mortality in premature very low birth weight or VLBW (< or = 1500 grams) infants.
    Matched MeSH terms: Sex Factors
  13. Global Burden of Disease Child and Adolescent Health Collaboration, Kassebaum N, Kyu HH, Zoeckler L, Olsen HE, Thomas K, et al.
    JAMA Pediatr, 2017 Jun 01;171(6):573-592.
    PMID: 28384795 DOI: 10.1001/jamapediatrics.2017.0250
    IMPORTANCE: Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.

    OBJECTIVE: To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.

    EVIDENCE REVIEW: Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.

    FINDINGS: Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3% (95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.

    CONCLUSIONS AND RELEVANCE: Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

    Matched MeSH terms: Sex Factors
  14. Rahman MM, Mahadeva S, Ghoshal UC
    World J Gastroenterol, 2017 Oct 07;23(37):6788-6801.
    PMID: 29085223 DOI: 10.3748/wjg.v23.i37.6788
    Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder, common in clinic and in the community. It has a significant impact on both society and patients' quality of life. The epidemiology, clinical presentation, and management of IBS may vary in different geographical regions due to differences in diet, gastrointestinal infection, socio-cultural and psycho-social factors, religious and illness beliefs, symptom perception and reporting. Although previous reviews and consensus reports on IBS in Asia have been published, Asia is quite diverse socio-demographically. In this context, India, Bangladesh and Malaysia share some similarities, including: (1) large proportion of the population living in rural areas; (2) rapid development and associated lifestyle changes in urban areas; and (3) dietary, cultural and religious practices. The present review explores the clinical and epidemiological data on IBS from these three major nations in South and South-East Asia. In-depth review of the literature revealed important differences between IBS in the East, as revealed by studies from these three countries, and the West; these include a predominantly rural profile, differences in bowel habit and symptom profile, raising concern with regards to diagnostic criteria and subtyping of IBS, higher dietary fiber consumption, frequent lactose malabsorption, parasitosis, and possible overlap between post-infectious IBS and tropical sprue. Moreover, the current perception on difference in prevalence of the disorder in these countries, as compared to the West, might be related to variation in survey methods.
    Matched MeSH terms: Sex Factors
  15. Sazlina SG, Zaiton A, Nor Afiah MZ, Hayati KS
    J Nutr Health Aging, 2012 May;16(5):498-502.
    PMID: 22555798
    OBJECTIVES: To determine the health related quality of life and its predictive factors among older people with non-communicable diseases attending primary care clinics.

    DESIGN: Cross-sectional study.

    SETTING: Three public primary care clinics in a district in Selangor, Malaysia.

    PARTICIPANTS: Registered patients aged 55 years and above.

    MEASUREMENTS: A face-to-face interview was conducted using a validated questionnaire of Medical Outcome Study 36-item short form health survey (SF-36). The outcome measure was the health related quality of life (HRQoL) and other factors measured were socio demography, physical activity, social support (Duke-UNC Functional Social Support Questionnaire), and presence of non-communicable diseases.

    RESULTS: A total of 347 participants had non-communicable diseases which included hypertension (41.8%), type 2 diabetes (33.7%), asthma (4.8%), hyperlipidaemia (1.7%), coronary heart disease (1.2%), and osteoarthritis (0.2%). Age ≥ 65 years old (OR =2.23; 95%CI=1.42, 3.50), single (OR=1.75; 95%CI=1.06,2.90), presence of co-morbid condition (OR=1.66; 95%CI=1.06, 2.61), and poorer social support (OR=2.11; 95%CI=1.27, 3.51; p=0.002) were significant predictors of poorer physical component of HRQoL . In predicting lower mental health component of HRQoL, the significant predictors were women (OR=2.28; 95%CI=1.44, 3.62), Indian ethnicity (OR=1.86; 95%CI=1.08, 3.21) and poorer social support (OR=2.71; 95%CI=1.63, 4.51). No interactions existed between these predictors.

    CONCLUSION: Older people with non-communicable diseases were susceptible to lower health related quality of life. Increasing age, single, presence of co-morbid conditions, and poorer social support were predictors of lower physical health component of HRQoL. While the older women, Indian ethnicity and poorer social support reported lower mental health component of HRQoL.

    Matched MeSH terms: Sex Factors
  16. Hemmati F, Dargahi L, Nasoohi S, Omidbakhsh R, Mohamed Z, Chik Z, et al.
    Behav Brain Res, 2013 Sep 1;252:415-21.
    PMID: 23777795 DOI: 10.1016/j.bbr.2013.06.016
    Alzheimer's disease (AD) as a neurodegenerative brain disorder is the most common cause of dementia. To date, there is no causative treatment for AD and there are few preventive treatments either. The sphingosine-1-phosphate receptor modulator FTY720 (fingolimod) prevents lymphocytes from contributing to an autoimmune reaction and has been approved for multiple sclerosis treatment. In concert with other studies showing the anti-inflammatory and protective effect of FTY720 in some neurodegenerative disorders like ischemia, we have recently shown that FTY720 chronic administration prevents from impairment of spatial learning and memory in AD rats. Here FTY720 was examined on AD rats in comparison to the only clinically approved NMDA receptor antagonist, Memantine. Passive avoidance task showed significant memory restoration in AD animals received FTY720 comparable to Memantine. Upon gene profiling by QuantiGene Plex, this behavioral outcomes was concurrent with considerable alterations in some genes transcripts like that of mitogen activated protein kinases (MAPKs) and some inflammatory markers that may particularly account for the detected decline in hippocampal neural damage or memory impairment associated with AD. From a therapeutic standpoint, our findings conclude that FTY720 may suggest new opportunities for AD management probably based on several modulatory effects on genes involved in cell death or survival.
    Matched MeSH terms: Sex Factors
  17. Park SC, Lee MS, Shinfuku N, Sartorius N, Park YC
    Aust N Z J Psychiatry, 2015 Sep;49(9):833-41.
    PMID: 25829482 DOI: 10.1177/0004867415579464
    The purpose of this study was to investigate whether there were gender-specific depressive symptom profiles or gender-specific patterns of psychotropic agent usage in Asian patients with depression.
    Matched MeSH terms: Sex Factors
  18. Brunton PJ, Donadio MV, Yao ST, Greenwood M, Seckl JR, Murphy D, et al.
    J Neurosci, 2015 Jan 14;35(2):666-77.
    PMID: 25589761 DOI: 10.1523/JNEUROSCI.5104-13.2015
    Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1β; IL-1β) in adulthood, compared with controls. IL-1β acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3β-androstanediol (3β-diol; 5α-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the "programmed" hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1β (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3β-diol normalized HPA axis responses to IL-1β in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5α-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5α-reductase and 3α-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1β. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5α-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner.
    Matched MeSH terms: Sex Factors
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