Emerging Progress in Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum: Challenges and Opportunities

Nausea and vomiting of pregnancy (NVP) is a common condition that affects up to 70% of pregnant women. Hyperemesis gravidarum (HG) is considered the serious form of NVP, which is reported in 0.3–10.8% of pregnant women. NVP has a relatively benign course, but HG can be linked with some poor maternal, fetal, and offspring outcomes. The exact causes of NVP and HG are unknown, but various factors have been hypothesized to be associated with pathogenesis. With the advance of precision medicine and molecular biology, some genetic factors such as growth/differentiation factor 15 (GDF15) have become therapeutic targets. In our review, we summarize the historical hypotheses of the pathogenesis of NVP and HG including hormonal factors, Helicobacter pylori, gastrointestinal dysmotility, placenta-related factors, psychosocial factors, and new factors identified by genetics. We also highlight some approaches to the management of NVP and HG, including pharmacological treatment, complementary treatment, and some supporting treatments. Looking to the future, progress in understanding NVP and HG may reduce the adverse outcomes and improve the maternal quality of life during pregnancy.

A Rare Case of Mitochondrial Neurogastrointestinal Encephalopathy

Mitochondrial Neuro Gastrointestinal Encephalopathy (MNGIE) is rare genetic disorer. It is characteristic by progressive gastrointestinal dysmotility, cachexia, opthalmoplegia and leucoencephalopathy.We hereby report a case of MNGIE in a female.

Light-Mediated Inhibition of Colonic Smooth Muscle Constriction and Colonic Motility via Opsin 3

Opsin photoreceptors outside of the central nervous system have been shown to mediate smooth muscle photorelaxation in several organs. We hypothesized that opsin receptor activation in the colon would have a similar effect and influence colonic motility. We detected Opsin 3 (OPN3) protein expression in the colonic wall and demonstrated that OPN3 was present in enteric neurons in the muscularis propria of the murine colon. Precontracted murine colon segments demonstrated blue light (BL) -mediated relaxation ex vivo. This photorelaxation was wavelength specific and was increased with the administration of the chromophore 9-cis retinal and a G protein receptor kinase 2 (GRK2) inhibitor. Light-mediated relaxation of the colon was not inhibited by L-NAME or tetrodotoxin (TTX). Furthermore, BL exposure in the presence of 9-cis retinal decreased the frequency of colonic migrating motor complexes (CMMC) in spontaneously contracting mouse colons ex vivo. These results demonstrate for the first time a receptor-mediated photorelaxation of colonic smooth muscle and implicate opsins as possible new targets in the treatment of spasmodic gastrointestinal dysmotility.

The Advantages and Disadvantages of Prokinetics

Prokinetics are medications that enhance gastrointestinal contractility; they improve the symptoms of patients with delayed gastrointestinal motility. Prokinetics have conventionally been used to stimulate gastrointestinal propulsion and to treat symptoms correlated with motility problems, including gastroparesis and constipation. 5-Hydroxytryptamine receptor 4 (5-HT4) agonists, such as cisapride, very effectively increased human gastrointestinal tract motility. However, cisapride sometimes induced serious tachyarrhythmia; the drug was thus withdrawn from the market. Thereafter, many prokinetics have been developed to treat delayed gastrointestinal motility. However, some exhibit serious side-effects. Recently, a new, highly selective serotonin receptor agonist, prucalopride, has been introduced; there is as yet no evidence of serious cardiac side- effects. The drug has been approved by the Food and Drug Administration to treat chronic constipation. Thus, recently introduced, highly selective agents appear to show promise as treatments for gastrointestinal dysmotility; there seem to be no serious side-effects.

Constipation and Syncope

A 43-year-old woman sought care for severe constipation associated with syncopal episodes. Her constipation alternated with explosive diarrhea. Chronic left-sided abdominal pain and severe bloating developed after eating. She was diagnosed with irritable bowel syndrome. After the initial onset of symptoms, nausea, bloating, and intractable vomiting developed. Symptoms were exacerbated by food and were partially relieved with vomiting. She had multiple episodes of bilious, undigested emesis per day. Trials of antiemetics and motility agents provided no substantial relief. She adopted a liquid diet, avoided solid foods, and eventually had a gastrostomy tube placed. She lost at least 15.9 kg over 2 years. Review of systems was significant for generalized fatigue and a burning sensation in her hands and feet. Her medical history was pertinent for Graves disease previously treated with remote thyroid radioablation, and she was now taking thyroid hormone replacement therapy. Neurologic examination findings were normal except for unreactive pupillary light reflexes. A gastrointestinal tract transit study showed persistently delayed colonic transit with mildly delayed gastric emptying. Autonomic reflex screening showed diffuse postganglionic sympathetic sudomotor, severe cardiovagal, and severe cardiovascular adrenergic impairment. Thermoregulatory sweat testing showed diffuse anhidrosis. Creatinine value was mildly increased. The serum was strongly positive for ganglionic (alpha 3) acetylcholine receptor-immunoglobulin G. The findings strongly suggested an autonomic autoimmune polyganglionopathy, with autoimmune gastrointestinal dysmotility as the predominant phenotype. She received intravenous immunoglobulin. She had complete resolution of her previous constipation, nausea, and vomiting. She regained 22.7 kg. Her gastrostomy tube was removed. Repeated gastrointestinal tract transit studies approached normal findings. Repeated autonomic testing and thermoregulatory sweat testing showed improvement. Over several months, the intravenous immunoglobulin dose was tapered. The patient remained asymptomatic for 8 years on long-term immunosuppression with azathioprine, she had a recurrence of her previous symptoms. Repeated gastrointestinal tract transit studies again showed delayed gastrointestinal tract emptying. Another intravenous immunoglobulin course controlled her symptoms, with normalization of gastrointestinal tract transit studies. Autoimmune gastrointestinal dysmotility can manifest as either hypomotility or hypermotility but most often presents as gastroparesis or pseudo-obstruction. Symptoms include nausea, vomiting, bloating, early satiety, diarrhea, constipation, and involuntary weight loss. It can be idiopathic or paraneoplastic. Risk factors for idiopathic cases include personal or family histories of autoimmunity.

Oropharyngeal Dysphagia and Impaired Motility of the Upper Gastrointestinal Tract—Is There a Clinical Link in Neurocritical Care?

Patients in the neurological ICU are at risk of suffering from disorders of the upper gastrointestinal tract. Oropharyngeal dysphagia (OD) can be caused by the underlying neurological disease and/or ICU treatment itself. The latter was also identified as a risk factor for gastrointestinal dysmotility. However, its association with OD and the impact of the neurological condition is unclear. Here, we investigated a possible link between OD and gastric residual volume (GRV) in patients in the neurological ICU. In this retrospective single-center study, patients with an episode of mechanical ventilation (MV) admitted to the neurological ICU due to an acute neurological disease or acute deterioration of a chronic neurological condition from 2011–2017 were included. The patients were submitted to an endoscopic swallowing evaluation within 72 h of the completion of MV. Their GRV was assessed daily. Patients with ≥1 d of GRV ≥500 mL were compared to all the other patients. Regression analysis was performed to identify the predictors of GRV ≥500 mL/d. With respect to GRV, the groups were compared depending on their FEES scores (0–3). A total of 976 patients were included in this study. A total of 35% demonstrated a GRV of ≥500 mL/d at least once. The significant predictors of relevant GRV were age, male gender, infratentorial or hemorrhagic stroke, prolonged MV and poor swallowing function. The patients with the poorest swallowing function presented a GRV of ≥500 mL/d significantly more often than the patients who scored the best. Conclusions: Our findings indicate an association between dysphagia severity and delayed gastric emptying in critically ill neurologic patients. This may partly be due to lesions in the swallowing and gastric network.

Moderate Physical Exercise Activates ATR2 Receptors, Improving Inflammation and Oxidative Stress in the Duodenum of 2K1C Hypertensive Rats

Background: In addition to the cardiovascular and renal systems, the gastrointestinal tract also contains angiotensin ATR1a, ATR1b, and ATR2. We previously observed that the 2Kidney-1Clip hypertension model elicits physical exercise and gastrointestinal dysmotility, which is prevented by renin-angiotensin system blockers. Here, we investigate the effect of physical exercise on inflammation, stress biomarkers, and angiotensin II receptors in the duodenum of 2K1C rats.Methods: Arterial hypertension was induced by the 2K1C surgical model. The rats were allocated in Sham, 2K1C, or 2K1C+Exercise groups. One week after surgery, they were submitted to a physical exercise protocol (running 5x/week, 60min/day). Next, we assessed their intestinal contractility, cytokine levels (TNF-α, IL-1β, and IL-6), oxidative stress levels (MPO, GSH, MDA, and SOD), and the gene expression of angiotensin receptors (ATR1A, ATR1B, and ATR2).Results: In comparison with the Sham group, the 2K1C arterial hypertension decreased (p<0.05) the intestinal contractility. In comparison with 2K1C, the 2K1C+Exercise group exhibited lower (p<0.05) MPO activity (22.04±5.90 vs. 78.95±18.09 UMPO/mg tissue) and higher (p<0.05) GSH concentrations in intestinal tissues (67.63±7.85 vs. 31.85±5.90mg NPSH/mg tissue). The 2K1C+Exercise group showed lower (p<0.05) cytokine levels in the intestine than 2K1C rats. In comparison with the Sham group, the 2K1C+Exercise rats showed higher (p<0.05) gene expression of ATR2 in the duodenum.Conclusion: 2K-1C hypertension elicits an oxidative stress and inflammation process in the duodenum. Physical exercise modulates the expression twice as much of ATR2 receptors, suggesting possible anti-inflammatory and antioxidant effects induced by exercise.