Pregnancy-induced hypertension--a particular pathogenic model. Similarities with other forms of arterial hypertension

Hypertension is in 85 to 90% of cases of unknown etiology, in spite of efforts undertaken by modern medicine to elucidate it. Numerous experimental studies were conducted in order to explain the pathogeny of this disease. Recent observations revealed that during therapy with anti-VEGF medication,used in treating different forms of cancer, hypertension and proteinuria occur, and at kidney level endothelial injuries appear similar to pregnancy-related hypertension. Antiangiogenic factors, such as sFlt-1, are produced during pregnancy-induced hypertension, especially in preeclampsia. They block the circulating VEGF. Consequently, proteinuria, and sometimes oedema occur together with hypertension. Renal injuries are of glomerular endotheliosis type. It is appreciated that one can draw a parallel between these pathologic situations, as is ablative treatment of antiangiogenic medication (anti-VEGF) and pregnancy-induced hypertension, preeclampsia, respectively. Since in pregnancy-induced hypertension angiogenic factors have an important role, we analyse their implication in other types of hypertension, in myocardial infarction, and in endothelial dysfunction in the course of CKD. The main pathogenic mechanism of pregnancy-induced hypertension that causes the disease is placental ischaemia. This is followed by the placental release of pressor substances that are involved both in generalised endotheliosis that characterizes the disease, and in hypertension. The prototype hypertension caused by renal ischaemia is renal artery stenosis. Both pregnancy-induced hypertension and hypertension in renal artery stenosis have a similar factor in their pathogeny, that is organ ischaemia with production of consecutive pressor substances. Since this ischaemic factor can intervene in other forms of hypertension, its characterisation becomes of importance at present. Thus, pregnancy-induced hypertension in pregnancy can represent a real pathogenic model of hypertension that is reflected in non-pregnancy hypertension. The paper presents the particularities of pregnancy-induced hypertension, as well as its parallelism with other types of hypertension that are determined by organ ischaemia or that produce ablation of angiogenic factors.     

Functional relevance of T helper 17 (Th17) cells and the IL-17 cytokine family in inflammatory bowel disease

The recent discovery and characterization of T helper 17 cells (Th17) and their signature cytokines (IL-17) represents a hallmark in T-cell immunobiology by providing a new distinctive pathway for the communication between adaptive and innate immunity. From the six members of the IL-17 cytokine family presently known, at least two have evident proinflammatory qualities and are involved in several chronic inflammatory disorders, including inflammatory bowel disease (IBD). IL-17A and IL-17F are abundantly found in inflamed IBD mucosa, suggesting their pivotal role in IBD. However, the precise implication of IL-17 cytokine family members in IBD pathogenesis and the mechanisms regulating their secretion are incompletely understood. Importantly, recent findings suggest that beyond IL-17 production-Th17 cells may secret a plethora of other effector cytokines such as IL-21, IL-22, and IL-9- which is in part induced by its own IL-9 production. However, the use of anti-IL-17 therapeutic strategies in experimental models of chronic inflammation results in disease-ameliorating effects suggesting their potential use in IBD patients. In this review article we discuss the latest findings on the role of Th17 cells and IL-17 family members in IBD immunopathology, as well as research perspectives.     

A novel peroxisome proliferator--activated receptor alpha/gamma dual agonist ameliorates dyslipidemia and insulin resistance in prediabetic rhesus monkeys

TAK-559, a newly developed non-thiazolidinedione, activates both peroxisome proliferator-activated receptors alpha and gamma. We investigated the effects of TAK-559 on dyslipidemia and insulin resistance in nonhuman primates. Five adult male obese prediabetic rhesus monkeys were studied on vehicle and after TAK-559 treatment (0.3, 1.0, 3.0 mg/kg per day) for a total of 12 weeks. No significant changes were observed in body weight and fasting plasma glucose, total plasma cholesterol, very low-density lipoprotein-triglyceride, and low-density lipoprotein cholesterol levels. TAK-559 treatment resulted in significant elevation of circulating high-density lipoprotein (HDL) cholesterol levels, consisting of an increase in large HDL particles and a decrease in small dense HDL particles. Nuclear magnetic resonance data exhibited a less atherogenic lipoprotein profile with treatment. Plasma triglyceride and apolipoprotein B-100 levels decreased, whereas apolipoprotein A-I increased during TAK-559 treatment. Hyperinsulinemia and insulin resistance (quantitative insulin sensitivity check index and homeostasis model assessment) were significantly corrected with the highest dose of 3.0 mg/kg per day in these prediabetic monkeys. In addition, no adverse effects on representative liver function parameters were observed during the study period. These results suggest that TAK-559 had beneficial effects on lipoprotein profiles and insulin sensitivity, without any side effect on body weight, which suggests that TAK-559 may provide a potentially safe approach for delaying the onset of type 2 diabetes mellitus and may reduce the risk of cardiovascular disease. The positive effects of TAK-559 in nonhuman primates have led to further clinical trials of TAK-559 in Europe and the United States.     

Change of appetite in patients with functional digestive disorder. Association with psychological disorders: A cross‐sectional study

Background and Aims

Changes in appetite are a frequent complaint in patients with functional gastrointestinal disorders (FGIDs). The aims of this study are to evaluate whether the changes in appetite are associated with specific FGIDs and to explore associations of these changes with symptoms of anxiety or depression.

Methods

This study included 1009 consecutive FGID patients (71% female), aged 48.9 years who all filled out a Rome III questionnaire for the evaluation of FGIDs, submitted to a psychological evaluation of symptoms of anxiety, and completed the Beck Depression Inventory questionnaire. The patients were classified according to their appetite change using a 7‐point grading scale and split into three groups: those with appetite loss, those with no change in appetite, and those with increased appetite.

Results

Among the 1009, 496 patients (49%) reported a change in appetite, of which 332 (33%) patients reported a decrease in appetite and 164 (16%) patients reported an increase in appetite. Appetite was not affected in 51% of patients. Changes in appetite depended on gender, body mass index and psychometric evaluation scores. Increased appetite did not have specific FGIDs associations, while decreased appetite was associated with esophageal, gastroduodenal, bowel, and anorectal symptoms. The presence of depressive symptoms was also a predictor for the majority of FGIDs in decreased appetite, while anxiety trait was significant for globus and dysphagia.

Conclusions

Decreased appetite was associated with FGIDs, especially in the presence of depressive symptoms. A reduced appetite would help to predict psychological disorders associated with FGIDs.

Financial disclosure

None declared.

Legal registration

This study was a registered study in the French National Drug Agency (ANSM, Agence Nationale de Securité du Medicamentet des produits de santé, Study Number 2016‐A01120‐51).

Competing interests

Michel Bouchoucha, Marinos Fysekidis, Florence Mary, Gheorghe Airinei, Cyriaque Bon, and Robert Benamouzig have no competitive interests.     

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

Background

Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed.

Living donor liver transplantation and hepatitis C

Preliminary results indicate that living donor liver transplantation (LDLT) recipients infected with HCV develop earlier and more severe recurrence than their cadaveric counterparts. The mechanisms underlying this observation are unknown, but could include hepatic regeneration, differences in LDLT recipient demographics, immune homology between donor and recipient, or other factors not previously considered. The optimum clinical approach is to consider LDLT in HCV-infected recipients only as a life-saving procedure and to attempt to eradicate HCV before LT to prevent recurrent infection.