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Augustin G, Krstulović J, Tavra A, Hrgović Z. Perforated peptic ulcer in pregnancy and puerperium: A systematic review. World J Gastrointest Surg 2025; 17:101682. [DOI: 10.4240/wjgs.v17.i4.101682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 02/18/2025] [Accepted: 03/05/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Peptic ulcer disease (PUD) during pregnancy is extremely rare. Perforated peptic ulcer (PPU) during pregnancy has high maternal and fetal mortality. Symptoms attributed to pregnancy and other diagnoses make the diagnosis of preoperative PPU during pregnancy and puerperium challenging.
AIM To identify predictive factors for early diagnosis and treatment, and the association between the diagnosis and maternal/neonatal outcomes.
METHODS We searched PubMed, PubMed Central, and Google Scholar. Articles were analyzed following preferred reporting items for systematic reviews and meta-analysis. The search items included: ‘ulcer’, ‘PUD’, ‘pregnancy’, ‘puerperium’, ‘postpartum’, ‘gravid’, ‘labor’, ‘perforated ulcer’, ‘stomach ulcer’, ‘duodenal ulcer’, ‘peptic ulcer’. Additional studies were extracted by reviewing reference lists of retrieved studies. We included all available full-text cases and case series. Demographic, clinical, obstetric, diagnostic and treatment parameters, and outcomes were collected.
RESULTS Forty-three cases were collected. The mean maternal age was 30.9 years; 36.6% were multiparous, and 63.4% were nulliparous or primiparous, with multiparas being older than primiparas. Peptic ulcer perforated in 44.2% of postpartum and 55.8% of antepartum patients. Antepartum PPU incidence increased with advancing gestation 2.3% in the first, 7% in the second, and 46.5% in the third trimester. The most common clinical findings were abdominal tenderness (72.1%), rigidity (34.9%), and distension (48.8%). Duodenal ulcer predominated (76.7%). In 79.5%, the time from delivery to surgery or vice versa was > 24 hours. The maternal mortality during the third trimester and postpartum was 10% and 31.6%, respectively. The trimester of presentation did not influence maternal mortality. The fetal mortality was 34.8%, with all deaths in gestational weeks 24-32.
CONCLUSION Almost all patients with PPU in pregnancy or puerperium presented during the third trimester or the first 8 days postpartum. Early intervention reduced fetal mortality but without influence on maternal mortality. Maternal mortality did not depend on the use of X-ray imaging, perforation location, delivery type, trimester of presentation, and maternal age. Explorative laparoscopy was never performed during pregnancy, only postpartum.
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Affiliation(s)
- Goran Augustin
- Department of Surgery, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Jure Krstulović
- Department of Surgery, University Hospital of Split, Split 21000, Croatia
- University of Split School of Medicine, Split 21000, Croatia
| | - Ante Tavra
- University of Split School of Medicine, Split 21000, Croatia
| | - Zrinka Hrgović
- University of Split School of Medicine, Split 21000, Croatia
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2
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Gastroparesis in pregnancy. Am J Obstet Gynecol 2022; 228:382-394. [PMID: 36088986 DOI: 10.1016/j.ajog.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 08/21/2022] [Accepted: 09/05/2022] [Indexed: 01/30/2023]
Abstract
Gastroparesis is a functional gastrointestinal disorder that more commonly affects women, with most cases being diagnosed during childbearing age. However, there is a paucity of data and guidelines to specifically highlight the epidemiology, disease course, maternal and fetal impact, and the management of existing gastroparesis during pregnancy. Apart from metoclopramide, there is no approved therapy specifically indicated for gastroparesis. More importantly, pregnant and breastfeeding women are excluded from clinical trials evaluating pharmacologic agents in the management of gastroparesis. This poses a real challenge to healthcare providers in counseling and managing patients with gastroparesis. In this systematic review, we summarize the current available literature and the knowledge gaps in the impact of pregnancy on gastroparesis and vice versa. We also highlight the efficacy and safety profiles of available pharmacologic and nonpharmacologic therapies in the management of patients with gastroparesis, with emphasis on judicious use of dietary approaches that are deemed relatively safe during pregnancy.
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Huang H, Zhang EB, Yi OY, Wu H, Deng G, Huang YM, Liu WL, Yan JY, Cai X. Sex-related differences in safety profiles, pharmacokinetics and tissue distribution of sinomenine hydrochloride in rats. Arch Toxicol 2022; 96:3245-3255. [PMID: 36040703 DOI: 10.1007/s00204-022-03368-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 12/12/2022]
Abstract
Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum (Thunb.) Rehd. et Wils which exhibits significant analgesic, anti-inflammatory, and immunosuppressive effects. Sinomenine hydrochloride (SH) preparations, classified as natural disease-modifying antirheumatic drugs, are currently available for the treatment of rheumatoid arthritis and other rheumatic diseases. Our toxicity evaluation demonstrated that the median lethal dose of SH in female Sprague-Dawley (SD) rats was over 11 times greater than that in male SD rats, revealing striking sex-linked differences in the safety profile of SH. The present study was designed to investigate differences in the pharmacokinetics (PKs) and tissue distribution of SH between male and female SD rats after a single oral dose of 25 mg/kg. PK and tissue distribution studies were performed using a validated UPLC-MS/MS method. The results showed that SH-treated SD female rats displayed markedly greater drug exposure, and SH exhibited a longer half-life and slower clearance rate than comparable studies in male rats. Moreover, the tissue distribution study confirmed that the sinomenine concentration in female rats was considerably greater in the internal organs than in male rats. Our study demonstrates, for the first time, significant sex-related differences in the safety profile and PKs of SH, which may be associated with a distinct sex-dependent metabolic mechanism of sinomenine.
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Affiliation(s)
- Hong Huang
- Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China
| | - Er-Bing Zhang
- Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.,Shenzhen Institute for Drug Control, Shenzhen, 518057, Guangdong, China
| | - Ou-Yang Yi
- Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China
| | - Han Wu
- Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China
| | - Guiming Deng
- Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China
| | - Yu-Ming Huang
- Hunan Zhengqing Pharmaceutical Group Co., Ltd., Huaihua, 418000, Hunan, China
| | - Wen-Liang Liu
- Shenzhen Institute for Drug Control, Shenzhen, 518057, Guangdong, China.
| | - Jian-Ye Yan
- Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
| | - Xiong Cai
- Department of Rheumatology of the First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
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Overduin TS, Page AJ, Young RL, Gatford KL. Adaptations in gastrointestinal nutrient absorption and its determinants during pregnancy in monogastric mammals: a scoping review protocol. JBI Evid Synth 2022; 20:640-646. [PMID: 35165214 DOI: 10.11124/jbies-21-00025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE The aim of this review is to characterize the current state of literature and knowledge regarding adaptations of gastrointestinal nutrient absorption, and the determinants of this absorption during pregnancy in monogastric mammals. INTRODUCTION Energy demands increase significantly during pregnancy due to the metabolic demands associated with placental and fetal growth, and the deposition of fat stores that support postnatal lactation. Previous studies have examined anatomical changes within the small intestine, but have focused on specific pregnancy stages or specific regions of the small intestine. Importantly, little is known about changes in nutrient absorption during pregnancy, and the underlying mechanisms that lead to these changes. An understanding of these adaptations will inform research to improve pregnancy outcomes for both mothers and newborns in the future. INCLUSION CRITERIA This review will include primary literature that describes gastrointestinal nutrient absorption and/or its determinants during pregnancy in monogastric mammals, including humans and rodents. Only data for normal pregnancies will be included, and models of pathology and illness will be excluded. Studies must include comparisons between pregnant animals at known stages of pregnancy, and non-pregnant controls, or compare animals at different stages of pregnancy. METHODS The following databases will be searched for literature on this topic: PubMed, Scopus, Web of Science, Embase, MEDLINE, and ProQuest Dissertations and Theses. Evidence screening and selection will be carried out independently by two reviewers, and conflicts will be resolved through discussion with additional members of the review team. Data will be extracted and presented in tables and/or figures, together with a narrative summary.
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Affiliation(s)
- Teunis Sebastian Overduin
- Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Nutrition, Diabetes and Gut Health, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
| | - Amanda J Page
- Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Nutrition, Diabetes and Gut Health, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Richard L Young
- Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Nutrition, Diabetes and Gut Health, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Kathryn L Gatford
- Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Nutrition, Diabetes and Gut Health, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
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Kovacic K, Zhang L, Nugent Liegl M, Pawela L, Simpson P, Sood MR. Gastric emptying in healthy children using the Spirulina breath test: The impact of gender, body size, and pubertal development. Neurogastroenterol Motil 2021; 33:e14063. [PMID: 33300658 DOI: 10.1111/nmo.14063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 10/10/2020] [Accepted: 11/17/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND There are no pediatric norms for gastric emptying (GE) measured by nuclear scintigraphy. The 13 C-labeled, stable isotope GE breath test (GEBT) is a non-radioactive alternative. We aimed to determine normative GEBT ranges in a cohort of healthy children and examine the influence of age, gender, puberty, and body surface area (BSA). METHODS Healthy children ages 8-18 years completed the [13 C]-Spirulina platensis GEBT after an overnight fast. Breath samples were collected at baseline, every 15 min × 1 h, then every 30 min for 4 h total. The 13 CO2 excretion rate was determined by the change in 13 CO2 /12 CO2 over time in each breath sample, expressed as kPCD (Percent 13 C Dose excreted/min). A mixed model with random time was used for multivariable analysis and outcome fit into a quadratic model. KEY RESULTS The 100 subjects completed the test meal within allotted time. Median (IQR) age was 13.5 (11.3-15.5) years; 51% were female. Females had lower 13 CO2 excretion rates (slower GE) than males across time (p < 0.001) while decreased excretion rates correlated with higher BSA (p = 0.015). Gender differences were also noted within pubertal stages with females showing slower GE. Multivariable analysis suggested that pre-pubertal children have faster GE than both peri- and post-pubertal groups (p < 0.0001). CONCLUSIONS & INFERENCES Gender, puberty, and BSA influence GE rates in healthy children more than age. Although further data are needed, pubertal stage and hormonal influences may be unique factors to consider when assessing GE in children.
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Affiliation(s)
- Katja Kovacic
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Liyun Zhang
- Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Melodee Nugent Liegl
- Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Louis Pawela
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Pippa Simpson
- Division of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Manu R Sood
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Medical College of Wisconsin, Milwaukee, WI, USA
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Alnoman A, Badeghiesh AM, Baghlaf HA, Dahan MH. Pregnancy, delivery, and neonatal outcomes among women with irritable bowel syndrome (IBS) an evaluation of over 9 million deliveries. J Matern Fetal Neonatal Med 2021; 35:5935-5942. [PMID: 33823718 DOI: 10.1080/14767058.2021.1903421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVE Evaluate the associations between irritable bowel syndrome (IBS) and pregnancy, delivery, and neonatal outcomes, using a population database cohort. METHODS We conducted a retrospective analysis utilizing the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database over 11 years from 2004 to 2014. A delivery cohort was created using ICD-9 codes. ICD-9 code 564.1 was used to extract the cases of IBS. Pregnant women with IBS (study group) were compared to pregnant women without IBS (control). A multivariate logistic regression model was used to adjust for statistically significant variables (p value <.05). RESULTS There were a total of 9,096,788 deliveries during the study period. Of those, 8962 pregnant women were found to have IBS. The prevalence of IBS increased from 47.96 to 172.68 per 100,000 women during the study period. Compared to the control group, women with IBS were more likely to be Caucasian, older, have higher incomes and private insurance plans (p < .0001, in all cases). In addition, they were more likely to be obese, smokers, hypertensive, IVF pregnancies, have multiple gestations, thyroid disorders, chronic interstitial cystitis, fibromyalgia and have psychiatric disorders (p < .0001 in all cases). Women with IBS were more likely to experience pregnancy-induced hypertension (aOR 1.11, 95% CI 1.02-1.21), preeclampsia (aOR 1.23, 95% CI 1.09-1.38), deep venous thrombosis (aOR 2.26, 95% CI 1.12-4.57), and gestational diabetes (aOR 1.1, 95% CI 1.002-1.22) compared to the non-IBS group. Congenital anomalies were encountered in 1.7% of the IBS group compared to 0.4% in the control group (aOR 2.57, 95% CI 2.13-3.09). CONCLUSION When controlling for confounding effects, IBS is associated with an increased risk for preeclampsia, DVT and increased risk for congenital malformation.
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Affiliation(s)
- Abdullah Alnoman
- Department of Obstetrics and Gynaecology, McGill University, Montreal, Canada.,Department of Obstetrics and Gynecology, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ahmad M Badeghiesh
- Department of Obstetrics and Gynaecology, McGill University, Montreal, Canada.,Department of Obstetrics and Gynecology, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Haitham A Baghlaf
- Division of Maternal-Fetal Medicine, Obstetrics & Gynaecology Department, University of Toronto, Toronto, Canada.,Department of Obstetrics and Gynecology, University of Tabuk, Tabuk, Saudi Arabia
| | - Michael H Dahan
- Division of Reproductive Endocrinology and Infertility, MUHC Reproductive Center, McGill University, Montreal, Canada
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7
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Gonzalez Z, Loganathan P, Sarosiek I, McCallum RW. Gender-Related Differences in Gastroparesis. Am J Med Sci 2020; 360:474-483. [DOI: 10.1016/j.amjms.2020.04.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 04/01/2020] [Accepted: 04/17/2020] [Indexed: 02/07/2023]
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Sprouse JC, Sampath C, Gangula PR. Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice. Antioxidants (Basel) 2020; 9:E582. [PMID: 32635208 PMCID: PMC7402187 DOI: 10.3390/antiox9070582] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 06/25/2020] [Accepted: 07/01/2020] [Indexed: 12/13/2022] Open
Abstract
Gastroparesis (Gp) is a multifactorial condition commonly observed in females and is characterized by delayed or rapid gastric emptying (GE). The role of ovarian hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus (T2DM) is completely unknown. The aims of our study are to investigate whether supplementation of 17β-estradiol (E2) or progesterone (P4) restores impaired nuclear factor erythroid 2-related factor 2 (Nrf2, an oxidative stress-responsive transcription factor) and nitric oxide (NO)-mediated gastric motility in ovariectomized (OVX) mice consuming a high-fat diet (HFD, a model of T2DM). Groups of OVX+HFD mice were administered daily subcutaneous doses of either E2 or P4 for 12 weeks. The effects of E2 and P4 on body weight, metabolic homeostasis, solid GE, gastric antrum NO-mediated relaxation, total nitrite levels, neuronal nitric oxide synthase (nNOSα), and its cofactor expression levels were assessed in OVX+HFD mice. HFD exacerbated hyperglycemia and insulinemia while accelerating GE (p < 0.05) in OVX mice. Exogenous E2, but not P4, attenuated rapid gastric emptying and restored gastric nitrergic relaxation, total nitrite levels, nNOSα, and cofactor expression via normalizing Nrf2-Phase II enzymes, inflammatory response, and mitogen-activated protein kinase (MAPK) protein expression in OVX+HFD mice. We conclude that E2 is beneficial in normalizing metabolic homeostasis and gastric emptying in obese, diabetic OVX mice consuming a fat-rich diet.
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Affiliation(s)
- Jeremy C. Sprouse
- School of Graduate Studies, Meharry Medical College, Nashville, TN 37208, USA;
| | - Chethan Sampath
- Department of ODS & Research, School of Dentistry, Nashville, TN 37208, USA;
| | - Pandu R. Gangula
- Department of ODS & Research, School of Dentistry, Nashville, TN 37208, USA;
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Al-Shboul OA, Mustafa AG, Omar AA, Al-Dwairi AN, Alqudah MA, Nazzal MS, Alfaqih MA, Al-Hader RA. Effect of progesterone on nitric oxide/cyclic guanosine monophosphate signaling and contraction in gastric smooth muscle cells. Biomed Rep 2018; 9:511-516. [PMID: 30546879 DOI: 10.3892/br.2018.1161] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 10/10/2018] [Indexed: 01/22/2023] Open
Abstract
Previous studies have shown that progesterone could inhibit muscle contraction in various sites of the gastrointestinal tract. The underlying mechanisms responsible for these inhibitory effects of progesterone are not fully known. The aim of the current study was to investigate the effect of progesterone on the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway and muscle contraction in the stomach. Single gastric smooth muscle cells from female Sprague-Dawley rats were used. The expression of progesterone receptor (PR) mRNA was analyzed by reverse transcription polymerase chain reaction. NO and cGMP levels were measured via specific ELISAs. Acetylcholine (ACh)-induced contraction of single gastric muscle cells preincubated with progesterone was measured via scanning micrometry in the presence or absence of the NO synthase inhibitor, Nω-Nitro-L-arginine (L-NNA), or guanylyl cyclase inhibitor, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and expressed as percent shortening from resting cell length. PR expression was detected in the stomach muscle cells. Progesterone inhibited ACh-induced gastric muscle cell contraction. Furthermore, progesterone increased NO and cGMP levels in single gastric muscle cells. Most notably, pre-incubation of muscle cells with either L-NNA or ODQ abolished the inhibitory action of progesterone on muscle contraction. These present observations suggest that progesterone promotes muscle cell relaxation in the stomach potentially via the NO/cGMP pathway.
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Affiliation(s)
- Othman A Al-Shboul
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Ayman G Mustafa
- Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Amal Abu Omar
- Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Ahmed N Al-Dwairi
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Mohammad A Alqudah
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Mona S Nazzal
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Rami A Al-Hader
- Department of Physiology and Biochemistry, Princess Basma Teaching Hospital, Faculty of Medicine, Jordan University of Science and Technology, Irbid 21110, Jordan
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Cross TWL, Kasahara K, Rey FE. Sexual dimorphism of cardiometabolic dysfunction: Gut microbiome in the play? Mol Metab 2018; 15:70-81. [PMID: 29887245 PMCID: PMC6066746 DOI: 10.1016/j.molmet.2018.05.016] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 05/22/2018] [Accepted: 05/24/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Sex is one of the most powerful modifiers of disease development. Clear sexual dimorphism exists in cardiometabolic health susceptibility, likely due to differences in sex steroid hormones. Changes in the gut microbiome have been linked with the development of obesity, type 2 diabetes, and atherosclerosis; however, the impact of microbes in sex-biased cardiometabolic disorders remains unclear. The gut microbiome is critical for maintaining a normal estrous cycle, testosterone levels, and reproductive function. Gut microbes modulate the enterohepatic recirculation of estrogens and androgens, affecting local and systemic levels of sex steroid hormones. Gut bacteria can also generate androgens from glucocorticoids. SCOPE OF REVIEW This review summarizes current knowledge of the complex interplay between sexual dimorphism in cardiometabolic disease and the gut microbiome. MAJOR CONCLUSIONS Emerging evidence suggests the role of gut microbiome as a modifier of disease susceptibility due to sex; however, the impact on cardiometabolic disease in this complex interplay is lacking. Elucidating the role of gut microbiome on sex-biased susceptibility in cardiometabolic disease is of high relevance to public health given its high prevalence and significant financial burden.
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Affiliation(s)
- Tzu-Wen L Cross
- Cardiovascular Research Center, University of Wisconsin-Madison, Madison, WI, 53705, United States; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, 53706, United States.
| | - Kazuyuki Kasahara
- Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, 53706, United States.
| | - Federico E Rey
- Cardiovascular Research Center, University of Wisconsin-Madison, Madison, WI, 53705, United States; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, 53706, United States.
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Gender-based personalized pharmacotherapy: a systematic review. Arch Gynecol Obstet 2017; 295:1305-1317. [PMID: 28378180 DOI: 10.1007/s00404-017-4363-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 03/29/2017] [Indexed: 01/03/2023]
Abstract
PURPOSE In general, male and female are prescribed the same amount of dosage even if most of the cases female required less dosage than male. Physicians are often facing problem on appropriate drug dosing, efficient treatment, and drug safety for a female in general. To identify and synthesize evidence about the effectiveness of gender-based therapy; provide the information to patients, providers, and health system intervention to ensure safety treatment; and minimize adverse effects. METHODS We performed a systematic review to evaluate the effect of gender difference on pharmacotherapy. Published articles from January 1990 to December 2015 were identified using specific term in MEDLINE (PubMed), EMBASE, and the Cochrane library according to search strategies that strengthen the reporting of observational and clinical studies. RESULTS Twenty-six studies fulfilled the inclusion criteria for this systematic review, yielding a total of 6309 subjects. We observed that female generally has a lower the gastric emptying time, gastric PH, lean body mass, and higher plasma volume, BMI, body fat, as well as reduce hepatic clearance, difference in activity of Cytochrome P450 enzyme, and metabolize drugs at different rate compared with male. Other significant factors such as conjugation, protein binding, absorption, and the renal elimination could not be ignored. However, these differences can lead to adverse effects in female especially for the pregnant, post-menopausal, and elderly women. CONCLUSION This systematic review provides an evidence for the effectiveness of dosage difference to ensure safety and efficient treatment. Future studies on the current topic are, therefore, recommended to reduce the adverse effect of therapy.
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12
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Matos JF, Americo MF, Sinzato YK, Volpato GT, Corá LA, Calabresi MFF, Oliveira RB, Damasceno DC, Miranda JRA. Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats. World J Gastroenterol 2016; 22:5761-5768. [PMID: 27433089 PMCID: PMC4932211 DOI: 10.3748/wjg.v22.i25.5761] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 05/07/2016] [Accepted: 06/02/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant (estrous cycle) and pregnant rats using noninvasive techniques.
METHODS: Female rats (n = 23) were randomly divided into (1) non-pregnant, (contractility, n = 6; transit, n = 6); and (2) pregnant (contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry (ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination.
RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions (3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying (168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control (54.23 ± 15.14 ng/mL and 129.96 ± 30.52 ng/mL vs 13.25 ± 6.31 ng/mL). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0 (44.3 ± 15.18 pg/mL vs 24.96 ± 5.96 pg/mL).
CONCLUSION: Gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying.
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13
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Estrogen alleviates acetic acid-induced gastric or colonic damage via both ERα- and ERβ-mediated and direct antioxidant mechanisms in rats. Inflammation 2015; 37:694-705. [PMID: 24323397 DOI: 10.1007/s10753-013-9786-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In order to demonstrate the possible protective effects of estrogen receptor (ER)-α and ERβ receptor subtypes in the pathogenesis of colonic and gastric oxidant damage, experimental ulcer and colitis were induced by acetic acid, and the animals were randomly divided as colitis, ulcer, and their corresponding non-ulcer and non-colitis control groups. Each group of rats was treated intramuscularly with the vehicle, selective ERα agonist propylpyrazole-triol (1 mg/kg), ERβ agonist diarylpropionitrile (1 mg/kg), non-selective ER agonist 17β estradiol (E2; 1 mg/kg), or E2 plus non-selective ER antagonist ICI-182780 (1 mg/kg). The results revealed that induction of ulcer or colitis resulted in systemic inflammation as assessed by increased levels of plasma TNF-α and IL-6 levels. In both tissues, the presence of oxidant damage was verified by histological analysis and elevated myleoperoxidase activity. In the colitis and ulcer groups, both ER agonists and the non-selective E2 reversed the oxidative damage in a similar manner. These findings indicate that estrogen acts via both ERα- and ERβ-mediated and direct antioxidant mechanisms, where both ER subtypes play equal and efficient roles in the anti-inflammatory action of estrogen, in limiting the migration of neutrophils to the inflamed tissue, reducing the release and activation of cytokines and thereby alleviating tissue damage.
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14
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Li TY, Li YK, Chan CM. Who are Prone to Develop Adverse Effects with Oral Tramadol? a Retrospective Cohort Study. HONG KONG J EMERG ME 2014. [DOI: 10.1177/102490791402100101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective Oral tramadol is a commonly prescribed analgesic in Hong Kong. Significant adverse effects are frequently observed in our locality. Our study aims to describe the rate of significant adverse effect that warrant discontinuation of oral tramadol and identify the risk factors for development of adverse effect. Design Retrospective cohort study. Methods Adult patients aged greater than 18 years old admitted to the emergency medicine ward of a large-scale local hospital in Hong Kong being prescribed with oral tramadol during in-hospital stay were recruited. Significant adverse effects during the hospital stay were observed as the outcome of interest. Results A total of 575 subjects were recruited. 29.9% experienced significant adverse effects likely related to tramadol. Age (p=0.006; odds ratio [OR] = 1.017, 95% confidence interval [CI] = 1.005-1.029) and sex (p=0.006; OR=1.696, 95% CI= 1.166-2.465) were statistically significant predictors of adverse effects after oral tramadol. Conclusion Our study suggests that female and increasing age patients are significant predictors for the development of adverse effect after taking oral tramadol. Possible adverse effects should be explained to the patients careful especially the higher risk groups. (Hong Kong j. emerg.med. 2014;21:3-9)
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Affiliation(s)
| | - YK Li
- Princess Margaret Hospital, Accident and Emergency Department, 2-10 Princess Margaret Hospital Road, Kwai Chung, N.T., Hong Kong
| | - CM Chan
- Princess Margaret Hospital, Accident and Emergency Department, 2-10 Princess Margaret Hospital Road, Kwai Chung, N.T., Hong Kong
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15
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Al-Shboul O, Mustafa A, Al-hashimi F. Non-genomic effects of progesterone on Rho kinase II in rat gastric smooth muscle cells. J Smooth Muscle Res 2013; 49:55-62. [PMID: 24133695 PMCID: PMC5137272 DOI: 10.1540/jsmr.49.55] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Various studies have shown that pregnancy is associated with gastrointestinal complaints
that might result from disturbance of the normal contractile pattern of smooth muscle.
Progesterone is an important steroid hormone, which plays a crucial role in female
pregnancy. Progesterone affects muscle cells by genomic mechanisms, through nuclear
receptors, and non-genomic mechanisms, through unidentified pathways. Non-genomic actions
were defined as those occurring within 10 min of progesterone exposure. The aim of the
present study was to investigate the non-genomic effect of progesterone on Rho kinase II
activity in gastric smooth muscle. Single smooth muscle cells of the stomach obtained from
Sprague Dawley rats were used. Dispersed gastric smooth muscle cells were treated with
progesterone or acetylcholine (ACh) separately. Cells designated for progesterone
treatment were incubated with 1 μM progesterone for 10 min. Rho kinase II expression and
both basal and ACh-induced Rho kinase II activity were measured via specifically designed
enzyme-linked immunosorbent assay (ELISA) and activity assay kits respectively in both
control and progesterone-treated groups. Progesterone inhibited the ACh-induced, but not
the basal, Rho kinase II activity in dispersed gastric smooth muscle cells without
affecting its expression level. This study suggested that progesterone can rapidly affect
the contractile activity of isolated gastric smooth muscle cells in rats via inhibition of
the Rho kinase II pathway.
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16
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Martin SA, McLanahan ED, El-Masri H, LeFew WR, Bushnell PJ, Boyes WK, Choi K, Clewell HJ, Campbell JL. Development of multi-route physiologically-based pharmacokinetic models for ethanol in the adult, pregnant, and neonatal rat. Inhal Toxicol 2012; 24:698-722. [DOI: 10.3109/08958378.2012.712165] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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17
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Freire AC, Basit AW, Choudhary R, Piong CW, Merchant HA. Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. Int J Pharm 2011; 415:15-28. [DOI: 10.1016/j.ijpharm.2011.04.069] [Citation(s) in RCA: 128] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2011] [Revised: 04/01/2011] [Accepted: 04/04/2011] [Indexed: 12/14/2022]
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18
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Marino M, Masella R, Bulzomi P, Campesi I, Malorni W, Franconi F. Nutrition and human health from a sex-gender perspective. Mol Aspects Med 2011; 32:1-70. [PMID: 21356234 DOI: 10.1016/j.mam.2011.02.001] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2010] [Revised: 01/25/2011] [Accepted: 02/18/2011] [Indexed: 02/07/2023]
Abstract
Nutrition exerts a life-long impact on human health, and the interaction between nutrition and health has been known for centuries. The recent literature has suggested that nutrition could differently influence the health of male and female individuals. Until the last decade of the 20th century, research on women has been neglected, and the results obtained in men have been directly translated to women in both the medicine and nutrition fields. Consequently, most modern guidelines are based on studies predominantly conducted on men. However, there are many sex-gender differences that are the result of multifactorial inputs, including gene repertoires, sex steroid hormones, and environmental factors (e.g., food components). The effects of these different inputs in male and female physiology will be different in different periods of ontogenetic development as well as during pregnancy and the ovarian cycle in females, which are also age dependent. As a result, different strategies have evolved to maintain male and female body homeostasis, which, in turn, implies that there are important differences in the bioavailability, metabolism, distribution, and elimination of foods and beverages in males and females. This article will review some of these differences underlying the impact of food components on the risk of developing diseases from a sex-gender perspective.
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Affiliation(s)
- Maria Marino
- Department of Biology, University Roma Tre, Viale Guglielmo Marconi 446, I-00146 Roma, Italy
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19
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Scandlyn MJ, Stuart EC, Rosengren RJ. Sex-specific differences in CYP450 isoforms in humans. Expert Opin Drug Metab Toxicol 2008; 4:413-24. [PMID: 18524030 DOI: 10.1517/17425255.4.4.413] [Citation(s) in RCA: 128] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The activity of various CYP isoforms is critical for maintaining the clinical effectiveness of many medications. Therefore, determining the sex-dependent activity of clinically relevant CYP families is highly important for optimal therapeutic effectiveness. OBJECTIVE This review examined the sex-dependent activity of CYP3A, CYP1A2, CYP2D6, CYP2C9, CYP2C19 and CYP2E1. METHODS This review searched for studies performed in humans and hormonal status was not a limiting factor. RESULTS/CONCLUSIONS The current evidence suggests that CYP2E1 and CYP1A2 activity is higher in males than females, while CYP3A, one of the most clinically relevant CYP isoforms, appears to have greater activity in females. Overall, more studies are needed to fully support these conclusions as there are many factors that influence drug metabolism and thus it is very difficult to isolate gender as a sole modulator of CYP activity.
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Affiliation(s)
- Marissa J Scandlyn
- University of Otago, Department of Pharmacology & Toxicology, Dunedin, New Zealand
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20
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Beckett EAH, McCloskey C, O'Kane N, Sanders KM, Koh SD. Effects of female steroid hormones on A-type K+ currents in murine colon. J Physiol 2006; 573:453-68. [PMID: 16581861 PMCID: PMC1779718 DOI: 10.1113/jphysiol.2006.107375] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K(+) channels serve to set the excitability of colonic muscles. We investigated regulation of Kv 4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv 4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.
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Affiliation(s)
- Elizabeth A H Beckett
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, MS 352, Reno, NV 89557, USA.
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21
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Güal O, Bozkurt A, Deniz M, Sungur M, Yeğen BC. Effect of sex steroids on colonic distension-induced delay of gastric emptying in rats. J Gastroenterol Hepatol 2004; 19:975-81. [PMID: 15304112 DOI: 10.1111/j.1440-1746.2004.03409.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM The objective of the present study was to examine the effect of gonadal hormones on gastric motor response to non-noxious and noxious stimuli of colonic distension. METHODS Male Wistar albino rats were used. Under ketamine anesthesia some rats underwent castration (n = 24), while the rest of the rats were sham-operated (n = 67) and divided into different groups (n = 7-8 per group). On the 15th day of surgery, liquid gastric emptying studies were commenced. RESULTS Non-noxious (P < 0.05) or noxious (P < 0.01) colonic distension inhibited gastric emptying rate. Estradiol pretreatment (20 micro g/kg per day, for 5 days, s.c.) inhibited gastric motility, while estradiol pretreatment or castration of the rats prior to noxious distension prevented the delay in gastric emptying. In contrast, blockade of testosterone receptors had no effect on the delay in gastric emptying induced by either modes of distension. CONCLUSIONS The results suggest that sex steroids have a modulatory role on the feedback control of gastric motility induced by noxious colonic distension.
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Affiliation(s)
- Omer Güal
- Department of General Surgery, Düzce School of Medicine, Abant Izzet Baysal University, Düzce, Turkey
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22
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Baccari MC, Bani D, Bigazzi M, Calamai F. Influence of relaxin on the neurally induced relaxant responses of the mouse gastric fundus. Biol Reprod 2004; 71:1325-9. [PMID: 15215200 DOI: 10.1095/biolreprod.104.029579] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The peptide hormone relaxin has been reported to depress the amplitude of contractile responses in the mouse gastric fundus by upregulating nitric oxide (NO) biosynthesis at the neural level. In the present study, we investigated whether relaxin also influenced nonadrenergic, noncholinergic (NANC) gastric relaxant responses in mice. Female mice in proestrus or estrus were treated for 18 h with relaxin (1 microg s.c.) or vehicle (controls). Mechanical responses of gastric fundal strips were recorded via force-displacement transducers. In carbachol precontracted strips from control mice and in the presence of guanethidine, electrical field stimulation (EFS) elicited fast relaxant responses that may be followed by a sustained relaxation. All relaxant responses were abolished by tetrodotoxin. Relaxin increased the amplitude of the EFS-induced fast relaxation without affecting either the sustained one or the direct smooth muscle response to papaverine. In the presence of the NO synthesis inhibitor L-N(G)-nitro arginine (L-NNA), that abolished the EFS-induced fast relaxation without influencing the sustained one, relaxin was ineffective. In strips from relaxin-pretreated mice, EFS-induced fast relaxations were enhanced in amplitude with respect to the controls, while sustained ones as well as direct smooth muscle responses to papaverine were not changed. Further addition of relaxin to the bath medium did not influence neurally induced fast relaxant responses, whereas L-NNA did. In conclusion, in the mouse gastric fundus, relaxin enhances the neurally induced nitrergic relaxant responses acting at the neural level.
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23
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Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol 2004; 44:499-523. [PMID: 14744256 DOI: 10.1146/annurev.pharmtox.44.101802.121453] [Citation(s) in RCA: 374] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The importance of reviewing and studying sex-based differences in pharmacologic parameters is demonstrated by the increasing data on gender variation in drug efficacy and toxicity profiles. Sex-based differences in the four major factors that contribute to interindividual pharmacokinetic variability--bioavailability, distribution, metabolism, and elimination--are theorized to stem from variations between men and women in factors such as body weight, plasma volume, gastric emptying time, plasma protein levels, cytochrome P450 activity, drug transporter function, and excretion activity. Sex-determined variations in pharmacodynamics have traditionally been more difficult to study, but a number of recent studies have explored these differences. This review examines the biologic basis of differences in pharmacokinetics and pharmacodynamics between the sexes and summarizes studies that have addressed these differences. As an example, sex-based variation in the efficacy and toxicity of antiretroviral therapy in human immunodeficiency virus (HIV)-infected patients is explored more thoroughly to illustrate some of the factors underlying sex-based differences in drug therapy.
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Affiliation(s)
- Monica Gandhi
- Division of Infectious Diseases, Department of Medicine, University of California San Francisco, San Francisco, California 94143-1352, USA.
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24
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Abstract
The irritable bowel syndrome (IBS) is characterized by altered bowel habits and abdominal discomfort in the absence of organic disease. No markers exist for IBS, and the definition of IBS is based on the presence of specific symptoms. The Rome II criteria for defining IBS include abdominal pain or discomfort for 12 weeks or longer, which need not be continuous, over the past 12 months plus two of the following: (1) relief of discomfort with defecation; (2) association of discomfort with altered stool frequency; and (3) association of discomfort with altered stool form. Nine percent to 22% of the population report symptoms consistent with IBS. IBS is the most prevalent digestive disease, representing 12% of visits to primary care physicians and 28% of referrals to gastroenterologists.
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Affiliation(s)
- William L Hasler
- Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, USA.
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25
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Liu CY, Chen LB, Liu PY, Xie DP, Wang PS. Effects of progesterone on gastric emptying and intestinal transit in male rats. World J Gastroenterol 2002; 8:338-41. [PMID: 11925620 PMCID: PMC4658379 DOI: 10.3748/wjg.v8.i2.338] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility.
METHODS: In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3 mL/kg) containing Na251CrO4 (0.5 μCi/mL) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol.
RESULTS: Low does of P (1 mg/kg, i.p.) enhanced the gastric emptying (75% ± 3%, P < 0.05) and high dose of P (5 mg/kg, i.p.) inhibit it (42% ± 11.2%, P < 0.01). P (1 mg/kg) increased the intestinal transit (4.2 ± 0.3, P < 0.05) while the higher dose (10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p.) inhibited the gastric emptying (23.5% ± 9.8%, P < 0.01). The inhibitory effects of P (20 mg/kg) (32% ± 9.7%, P < 0.05) and OT (0.8 mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17% ± 9.4%, P < 0.01).
CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.
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Affiliation(s)
- Chuan-Yong Liu
- Department of Physiology, School of Medicine, Shandong University, Jinan 250012, Shandong Province, China.
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26
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Bani D, Baccari MC, Quattrone S, Nistri S, Calamai F, Bigazzi M, Bani Sacchi T. Relaxin depresses small bowel motility through a nitric oxide-mediated mechanism. Studies in mice. Biol Reprod 2002; 66:778-84. [PMID: 11870086 DOI: 10.1095/biolreprod66.3.778] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Gastrointestinal motility is reduced and the incidence of functional gastrointestinal disorders is increased in pregnancy, possibly due to hormonal influences. This study aims to clarify whether the hormone relaxin, which attains high circulating levels during pregnancy and has a nitric oxide-mediated relaxant action on vascular and uterine smooth muscle, also reduces bowel motility and, if it does, whether nitric oxide is involved. Female mice in proestrous or estrous were treated for 18 h with relaxin (1 microg s.c.) or vehicle (controls). Isolated ileal preparations from both groups were used to record contractile activity, either basal or after acute administration of relaxin (5 x 10(-8) M). Drugs inhibiting nitric oxide biosynthesis or neurotransmission were used in combination with relaxin. Expression of nitric oxide synthase isoforms by the ileum was assessed by immunocytochemistry and Western blot analysis. Relaxin caused a clear-cut decay of muscle tension and a reduction in amplitude of spontaneous contractions upon either chronic administration to mice or acute addition to isolated ileal preparations. These effects were significantly blunted by N(G)-nitro-L-arginine, but not by the neural blockers we used. Moreover, relaxin increased the expression of nitric oxide synthases II and III, but not synthase I. Relaxin markedly inhibits ileal motility in mice by exerting a direct action on smooth muscle through the activation of intrinsic nitric oxide biosynthesis.
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Affiliation(s)
- Daniele Bani
- Department of Anatomy, Histology, and Forensic Medicine, University of Florence, Florence, Italy.
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Shah S, Nathan L, Singh R, Fu YS, Chaudhuri G. E2 and not P4 increases NO release from NANC nerves of the gastrointestinal tract: implications in pregnancy. Am J Physiol Regul Integr Comp Physiol 2001; 280:R1546-54. [PMID: 11294780 DOI: 10.1152/ajpregu.2001.280.5.r1546] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In women, during pregnancy, there is decreased motility of the gastrointestinal tract leading to a delay in gastric emptying and an increase in colonic transit time. Whether the rise in estradiol (E2) or progesterone (P4) is responsible for this effect is controversial. As the nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves is responsible for modulating gastrointestinal motility in vivo, the purpose of this study was to evaluate whether the increased release of nitric oxide (NO) from the nitrergic component of the NANC nerves innervating the gastric fundus and colon that occurs during late pregnancy in rats is mediated by E2 or P4. Ovariectomized rats treated with E2 or P4 alone or in combination were used for our studies. We also wanted to assess the cellular and molecular mechanisms involved. The NANC activity was studied by assessing changes in tone after application of electric field stimulation (EFS). The role of NO was determined by observing the effects of EFS in the presence and absence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the reversibility of the effects of L-NAME by L-arginine. Our studies indicated that there was increased magnitude of relaxation of isolated strips of rat gastric fundus and rat colon after application of EFS to tissues obtained from animals treated with E2 alone or a combination of E2 + P4 but not from those treated with P4 alone. L-NAME attenuated relaxation responses in E2- and E2 + P4-treated animals. To elucidate whether the increased NO release may be due to an increase in neuronal NOS (nNOS) protein, we used both Western blot analysis and immunohistochemistry. We also used RT-PCR to determine whether there was an increase in nNOS mRNA after treatment with sex steroids. In nonpregnant animals, nNOS was detected by Western blot in the fundus and the colon and was barely detectable in the ileum. In pregnancy, there was an increase in nNOS in both the gastric fundus and the colon. The nNOS protein was also increased in ovariectomized animals treated with either E2 alone or E2 + P4 but not P4 alone when compared with ovariectomized animals receiving vehicle. Our results indicated that there was an increase in nNOS protein that was localized to the neurons of the myenteric plexus in the gastric fundus and colon in E2- and E2 + P4-treated animals, but this increase was not observed in animals treated with P4 alone. This increase in nNOS protein was accompanied by an increase in nNOS mRNA. These results suggest the possibility that E2, rather than P4, may be responsible for the delay in gastric emptying and increase in colonic transit time observed in pregnancy.
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Affiliation(s)
- S Shah
- Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, California 90095, USA
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28
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Shah S, Hobbs A, Singh R, Cuevas J, Ignarro LJ, Chaudhuri G. Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves. Am J Physiol Regul Integr Comp Physiol 2000; 279:R1478-85. [PMID: 11004018 DOI: 10.1152/ajpregu.2000.279.4.r1478] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
This study evaluated whether increased release of nitric oxide (NO) from the nitrergic component of the nonadrenergic, noncholinergic (NANC) nerves may be partly responsible for the decrease in gastrointestinal motility observed during pregnancy. Segments of fundal strip, ileum, and colon were obtained from nonpregnant rats, rats in midpregnancy (days 9-11), and rats in late pregnancy (days 18-20). NANC activity was studied by assessing changes in tone after application of electric field stimulation (EFS). The role of NO was determined by observing the effects of EFS in the presence and absence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and the reversibility of the effects of L-NAME by L-arginine. The magnitude of change in cGMP levels in the tissues after application of EFS was also assessed. Our studies indicate that there was increased magnitude of relaxation of isolated strips of rat gastric fundus and rat colon, after application of EFS to tissues obtained only from animals in late pregnancy. These results paralleled the changes in cGMP levels in tissues. NOS activity in the gastric fundus was significantly increased in animals in late pregnancy compared with nonpregnant controls. Our studies suggest that the delay in gastric emptying and increase in colonic transit time observed in rats during pregnancy may be caused in part by increased activity of the nitrergic component of the NANC nerves innervating these organs.
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Affiliation(s)
- S Shah
- Department of Obstetrics and Gynecology, University of California, Los Angeles, California 90095-1740, USA
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29
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Grewal M, Cuevas J, Chaudhuri G, Nathan L. Effects of calcitonin gene-related peptide on vascular resistance in rats: role of sex steroids. THE AMERICAN JOURNAL OF PHYSIOLOGY 1999; 276:H2063-8. [PMID: 10362688 DOI: 10.1152/ajpheart.1999.276.6.h2063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
It has been demonstrated in reflex-intact animals that the sensitivity to calcitonin gene-related peptide (CGRP) is increased during pregnancy and that this action is mediated by sex steroids but not by nitric oxide (NO). We assessed the effects of CGRP in the following groups of anesthetized ganglion-blocked rats: 1) pregnant, 2) ovariectomized, and 3) ovariectomized and treated with estradiol and progesterone. Changes in mean arterial pressure (MAP) were assessed after the administration of varying doses of CGRP. Decreases in MAP after CGRP administration were significantly greater in pregnant rats and ovariectomized rats administered sex steroids than in ovariectomized controls. The CGRP antagonist CGRP8-37 produced a pressor response of similar magnitude in both pregnant and ovariectomized rats. We also assessed the effects of CGRP and the modulating role of NO in the isolated uterine vascular bed preparation. CGRP reduced perfusion pressure to a greater degree in ovariectomized animals treated with sex steroids than in ovariectomized animals. This response was attenuated by pretreatment with an NO synthesis inhibitor. CGRP8-37 produced a similar increase in perfusion pressure in both groups. We conclude that 1) the increased vascular sensitivity observed during pregnancy or after treatment with sex steroids is in part mediated by NO, and 2) CGRP8-37 has a vasoconstrictor action of its own.
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Affiliation(s)
- M Grewal
- Department of Obstetrics and Gynecology, University of California, Los Angeles, California 90095, USA
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30
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Günal O, Yeğen C, Aktan AO, Yalin R, Yeğen BC. Gastric functions in portal hypertension. Role of endothelin. Dig Dis Sci 1996; 41:585-90. [PMID: 8617140 DOI: 10.1007/bf02282345] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This study investigated the effects of portal hypertension on gastric motor and secretory functions and the role of endothelin in rats. Control; sham-operated; endothelin-A receptor blocker, BQ 485 (1 microgram/kg)-treated; portal hypertensive; and portal hypertension +, endothelin-A receptor blocker-treated rats were subjected to tests of gastric secretory, motor, and mucosal function studies as well as gastric wall polymorphonuclear infiltration. Portal hypertension was induced by partial portal vein ligation. Portal hypertension suppressed gastric acid and total fluid secretion and delayed gastric emptying. An increase in mucosal permeability and no alteration in gastric wall myeloperoxidase activity were observed. The effects of portal hypertension on gastric secretory, motor, and mucosal functions were reversed by treatment with endothelin-A receptor blocker, BQ-485. It is concluded that portal hypertension suppresses the gastric motor and secretory functions and endothelin plays an important role in the pathophysiology of gastric alterations associated with portal hypertension.
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Affiliation(s)
- O Günal
- Department of General Surgery, Marmara University, School of Medicine, Istanbul, Turkey
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