Dietary nitrate attenuates high-fat diet-induced obesity via mechanisms involving higher adipocyte respiration and alterations in inflammatory status.

Emerging evidence indicates that dietary nitrate can reverse several features of the metabolic syndrome, but the underlying molecular mechanisms still remain elusive. The aim of the present study was to explore mechanisms involved in the effects of dietary nitrate on the metabolic dysfunctions induced by high-fat diet (HFD) in mice. Four weeks old C57BL/6 male mice, exposed to HFD for ten weeks, were characterised by increased body weight, fat content, increased fasting glucose and impaired glucose clearance. All these metabolic abnormalities were significantly attenuated by dietary nitrate. Mechanistically, subcutaneous primary mouse adipocytes exposed to palmitate (PA) and treated with nitrite exhibited higher mitochondrial respiration, increased protein expression of total mitochondrial complexes and elevated gene expression of the thermogenesis gene UCP-1, as well as of the creatine transporter SLC6A8. Finally, dietary nitrate increased the expression of anti-inflammatory markers in visceral fat, plasma and bone marrow-derived macrophages (Arginase-1, Egr-2, IL-10), which was associated with reduction of NADPH oxidase-derived superoxide production in macrophages. In conclusion, dietary nitrate may have therapeutic utility against obesity and associated metabolic complications possibly by increasing adipocyte mitochondrial respiration and by dampening inflammation and oxidative stress.

[Intra-cystic renal calcium milk]. / Le cas clinique du mois. Lait calcique intra-kystique renal.

Intra-cystic renal calcium milk is a rare entity. The authors report a clinical case, and describe the radiographic and tomodensitometric appearances. This 50 year old patient has been followed up for more than ten years for urinary lithiasis with recurrent pain.

Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis.

BACKGROUND AND PURPOSE: Pentoxifylline is in clinical trials for non-alcoholic fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of pentoxifylline were assessed in a murine model of obesity and type 2 diabetes. EXPERIMENTAL APPROACH: Pentoxifylline (100 mg·kg(-1) ·day(-1)) was administered for 4 days or 3 weeks in lean and obese/diabetic ob/ob mice. Plasma lipids, glucose, other metabolites and relevant enzymes were measured by standard assays. Hepatic lipids in vivo were assessed with magnetic resonance spectroscopy and by histology. Hepatic extracts were also analysed with RT-PCR and Western blotting. KEY RESULTS: Four days of pentoxifylline treatment slightly increased liver lipids in ob/ob mice. After 3 weeks, pentoxifylline exacerbated fatty liver and plasma transaminases in ob/ob mice but did not induce liver steatosis in lean mice. Plasma glucose was highest in fed, but not fasted, ob/ob mice treated with pentoxifylline. During the first 10 min of an oral glucose tolerance test, blood glucose increased more rapidly in pentoxifylline-treated mice. Jejunal expression of glucose transporter 2 isoform was increased in pentoxifylline-treated obese mice. Hepatic activity of carbohydrate response element binding protein (ChREBP) increased after pentoxifylline in ob/ob, but not lean, mice. Hepatic expression of lipogenic enzymes was highest in pentoxifylline-treated ob/ob mice. However, pentoxifylline reduced markers of oxidative stress and inflammation in ob/ob liver. CONCLUSION AND IMPLICATIONS: Pentoxifylline exacerbated fatty liver in ob/ob mice through enhanced intestinal glucose absorption, increased postprandial glycaemia and activation of hepatic lipogenesis. Long-term treatment with pentoxifylline could worsen fatty liver in some patients with pre-existing hyperglycaemia.

[Treatment of severe acute asthma in adults]. / Traitement des asthmes aigus graves de l'adulte.

Although abnormal blood gases are unusual in status asthmaticus, hypercapnia indicates a considerable increase in bronchial resistance. The authors report their experience of 106 personal cases of acute severe asthma. Emergency management of acute respiratory failure consisted in symptomatic therapy (low rate oxygen or mechanical ventilation after nasal intubation). Corticosteroids, rehydration, antibiotics and beta-2 adrenergic agents were associated. Mechanical ventilation was necessary in patients who developed alterations of consciousness or PaCO2 above 60 mm Hg (8 kPa). In respirator-patients, sedative drugs were needed. Terbutaline and salbutamol were occasionally beneficial but epinephrine remains the drug of choice. In our series of 106 cases (79 with hypercapnia) the overall mortality was 3.8 p. 100. Of the 33 cases who underwent mechanical ventilation, there were 4 deaths (12 p. 100). A review of the literature showed a much higher mortality in other series.

[Changes in the electrocardiogram in status asthmaticus]. / Les modifications de l'électrocardiogramme dans l'état de mal asthmatique.

The aim of this study, based on the electrocardiographic analysis of 42 patients in status asthmaticus, is to define the basic criteria which may be used as a basis for electrocardiographic differential diagnosis. The following ECG changes were observed: the pulmonary "p" wave is common, sometimes with exaggerated amplitude in peripheral leads, however, in the precordial leads, the voltage of the "p" wave is reduced; most cases have a vertical heart with clockwise rotation and mild right axis deviation, S1 Q2 Q3 and the transitional zone displaced to the left. Ten cases also had a S1 S2 S3 appearance and three cases showed Q1 Q2 Q3, simulating myocardial infarction; there is poor progression of the R wave in the precordial leads and marked persistence of the S wave in the left precordial leads. In some cases, a QS complex dominates the right precordial leads. A variation in the amplitude of the QRS with the respiratory rhythm is often seen in V1 and V2; ventricular repolarization shows a lowered J point with an upward oblique ST segment in the peripheral leads. However, in the precordial leads, the repolarization is normal except for three cases which presented a frank hypokalaemia. The mechanism of these electrocardiographic changes appears to depend on the vertical position of the heart caused by over expansion of the lungs and pulmonary arterial hypertension. The elements of the electrocardiographic differential diagnosis with myocardial infarction and pulmonary embolism are discussed.

[Surgically treated chronic aortic valve insufficiency. Long term results. Surgical indications]. / L'insuffisance aortique chronique opérée. Le devenir à long terme - Les indications opératoires.

The timing of surgery in chronic aortic regurgitation depends to a large extent on the operative results that may be expected in this type of valve disease. In 88 cases of chronic aortic regurgitation submitted to surgery there were 6 operative deaths (6.8%). Five years after operation the actuarial survival was 58% for the whole of the group and 68% for cases of rheumatic aortic regurgitation. Analysis of the causes of failures, late deaths, persistence or recurrence of severe impairment of activity, and of serious disturbances of ventricular rhythm, showed that the most important cause was myocardial dysfunction, which was responsible for two thirds of the bad results. Analysis of the late prognosis as a function of the various pre-operative parameters revealed the bad influence of cardiomegaly as measured by radiological examination (cardio-thoracic ratio and cineangiography) and of disturbances in left ventricular function. The actuarial survival curves showed very significant differences according to whether the cardiothoracic ratio was greater or smaller than 58%, and according to the amount of heart failure pre-operatively. Similarly, an end-diastolic volume index of 240 ml/m2 and an ejection fraction less than. 40 seemed to be serious findings. These facts, taken in conjunction with the natural history of this valve lesion, suggest that the indications for surgery should not only be symptomatic aortic regurgitation but also well tolerated regurgitation in which cardiomegaly, end-diastolic volume and/or the ejection fraction have reached a certain level.