Effects of ketogenic diet and ketone bodies on the cardiovascular system: Concentration matters

Ketone bodies have emerged as central mediators of metabolic health, and multiple beneficial effects of a ketogenic diet, impacting metabolism, neuronal pathologies and, to a certain extent, tumorigenesis, have been reported both in animal models and clinical research. Ketone bodies, endogenously produced by the liver, act pleiotropically as metabolic intermediates, signaling molecules, and epigenetic modifiers. The endothelium and the vascular system are central regulators of the organism’s metabolic state and become dysfunctional in cardiovascular disease, atherosclerosis, and diabetic micro- and macrovascular complications. As physiological circulating ketone bodies can attain millimolar concentrations, the endothelium is the first-line cell lineage exposed to them. While in diabetic ketoacidosis high ketone body concentrations are detrimental to the vasculature, recent research revealed that ketone bodies in the low millimolar range may exert beneficial effects on endothelial cell (EC) functioning by modulating the EC inflammatory status, senescence, and metabolism. Here, we review the long-held evidence of detrimental cardiovascular effects of ketoacidosis as well as the more recent evidence for a positive impact of ketone bodies—at lower concentrations—on the ECs metabolism and vascular physiology and the subjacent cellular and molecular mechanisms. We also explore arising controversies in the field and discuss the importance of ketone body concentrations in relation to their effects. At low concentration, endogenously produced ketone bodies upon uptake of a ketogenic diet or supplemented ketone bodies (or their precursors) may prove beneficial to ameliorate endothelial function and, consequently, pathologies in which endothelial damage occurs.     

Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies

Growth arrest and DNA damage-inducible gene 34 (GADD34) is an inducible cofactor of protein phosphatase 1, which has an important role in the unfolded protein response. GADD34 has been shown to be necessary for type I interferon and proinflammatory cytokine production in response to viral infection in murine models. We investigate the expression of GADD34 in rheumatoid arthritis (RA), in which proinflammatory cytokines have an important pathogenic role. The objective of this study was to evaluate the potential of GADD34 expression as a biomarker in RA patients. We report a case–control study on GADD34 gene expression in peripheral blood mononuclear cells of patients (n?=?75) with RA and age- and sex-matched healthy controls (n?=?25). The study was approved by the relevant local ethics committees. GADD34 gene expression level in peripheral blood mononuclear cells was measured by quantitative PCR and analyzed with Mann–Whitney test. The relation between GADD34 gene overexpression and clinical or biological characteristics was analyzed with univariate and multivariate analysis. GADD34 gene expression was significantly higher in RA patients compared with healthy controls (p?≤?0.001). Interestingly, GADD34 overexpression in PBMC of patients was related to the presence of circulating anti-citrullinated protein antibodies (p?=?0.030). Data of this study strengthen the evidence of an unfolded protein response during the course of RA and provide an insight of the potential interest in GADD34 as a relevant marker for RA.     

Long-term (up to 18 years) clinical and echocardiographic results of mitral balloon valvuloplasty in children in comparison with adult population

AIMS: The purpose of this study was to assess the safety, efficacy, and long-term results (up to 18 years) of mitral balloon valvuloplasty (MBV) in children in comparison to adults. METHODS: 57 children age < or = 18 years (group A) and 474 adult patients (group B) who underwent successful MBV and were followed up for a mean 8.5 +/- 4.8 (range 1.5-18) years were analyzed. RESULTS: Patients in group A had a lower mitral echocardiographic score (echo score), 7.6 +/- 1.3 vs. 8.1 +/- 1 (P = 0.0005); smaller Doppler mitral valve area (MVA), 0.82 +/- 0.16 cm(2) vs. 0.92 +/- 0.17 cm(2) (P < 0.0001); and higher mitral valve gradient, 15.2 +/- 2.3 mmHg vs. 14.3 +/- 2.1 mmHg (P = 0.0003), than group B. Immediately after MBV, group A had larger MVA whether measured by catheter, 1.99 +/- 0.57 cm(2) vs. 1.8 +/- 0.52 cm(2) (P < 0.001), or by Doppler, 2.0 +/- 0.27 cm(2) vs. 1.97 +/- 0.28 cm(2) (P < 0.01), and similar complication rates, compared to group B. After a mean follow-up of 8.5 +/- 4.8 (range 1.5-18 years), restenosis in group A was 26% vs. 31% for group B (P = 0.41). Echo score > 8 (P = 0.046) was a predictor of restenosis in children and echo score > 8 (P < 0.0001) and previous surgery (P = 0.043) were predictors of restenosis in adults. Actuarial freedom from restenosis at 10, 15, and 18 years for groups A and B were 78%+/- 7%, 64%+/- 9%, and 18%+/- 14% and 77%+/- 2%, 43%+/- 4%, and 17%+/- 4%, respectively (P = 0.26). Event-free survival rates at 10, 15, and 18 years were 87%+/- 6%, 62%+/- 1%, and 20%+/- 2% versus 87%+/- 1%, 51%+/- 4%, and 20%+/- 5% for groups A and B, respectively (P = 0.51). Postprocedure MVA < 2.0 cm(2) (P = 0.043) and previous surgery (P = 0.03) were identified as predictors of events in children. Echo score > 8 (P < 0.0001) and prevalvuloplasty AF (P = 0.03) were identified as predictors of events in adults. CONCLUSION: MBV is safe and effective in children with rheumatic MS. It provides better immediate results than in adults and excellent long-term results that are comparable to those seen in adults.     

Hepatitis B and E Co-Primary Infections in an HIV-1-Infected Patient

We report an autochthonous hepatitis E virus (HEV)-hepatitis B virus co-primary infection in a 41-year-old man having sex with men and infected with human immunodeficiency virus (HIV). This case prompts testing for HEV in HIV-infected patients with acute hepatitis even if primary infection with another hepatitis virus is diagnosed.     

Evaluation of healing activity of PVA/chitosan hydrogels on deep second degree burn: Pharmacological and toxicological tests

Hydrogel based on poly(vinyl alcohol) containing 0.25% of chitosan was synthesized by gamma irradiation and evaluated as wound dressing material in a burn rat model. Histological analyses, Primary Irritation Index (P.I.I.) and Ocular Irritation Index (O.I.I.) were investigated. The comparative study showed that the wounds treated with PVA/chitosan hydrogel healed on the 9th day, while those treated with paraffin gauze dressing and cotton gauze healed on the 16th day. Histological analysis showed that new granulation tissue and epithelialization progressed better in wound treated with hydrogel PVA/chitosan. The determined values of P.I.I. and O.I.I. of the PVA/chitosan hydrogel were, respectively 0.5 and zero. These values indicate that the PVA/chitosan hydrogel can be considered as non-irritating to the skin.     

Evolution of wild cereals during 28 years of global warming in Israel

Climate change is a major environmental stress threatening biodiversity and human civilization. The best hope to secure staple food for humans and animal feed by future crop improvement depends on wild progenitors. We examined 10 wild emmer wheat (Triticum dicoccoides Koern.) populations and 10 wild barley (Hordeum spontaneum K. Koch) populations in Israel, sampling them in 1980 and again in 2008, and performed phenotypic and genotypic analyses on the collected samples. We witnessed the profound adaptive changes of these wild cereals in Israel over the last 28 y in flowering time and simple sequence repeat allelic turnover. The revealed evolutionary changes imply unrealized risks present in genetic resources for crop improvement and human food production.     

First report of natural infection in hedgehogs with Leishmania major, a possible reservoir of zoonotic cutaneous leishmaniasis in Algeria

We report here the first known cases of natural infection of hedgehogs with Leishmania major. Cutaneous leishmaniasis is an important public health problem in the area of M'sila, a semi-arid province in Algeria's northern Sahara, where two species of hedgehog live, Atelerix algirus and Paraechinus aethiopicus. The aim of this research was to survey Leishmania infection in these hedgehogs and evaluate whether they were reservoir hosts of Leishmania in an endemic zoonotic focus of leishmaniasis. Serological and molecular methods were used to determine the presence of Leishmania in 24 hedgehogs caught directly by hand and identified at species level as 19 A. algirus and 5 P. aethiopicus. Specific anti-Leishmania antibodies were detected in 29.2% of individuals by Western blot and in 26.3% by ELISA. The real-time PCR performed in spleen, ear and blood samples detected Leishmania spp. DNA in 12.5% of the individuals, one A. algirus and two P. aethiopicus. Three skin and two spleen samples of these animals were found to be parasitized and were identified by molecular test as L. major. Considering our results, it is suggested that hedgehogs have a potential epidemiological role as reservoir hosts of L. major.     

Primary non-Hodgkin's lymphoma of the thyroid. A case report and review of the literature]

The authors report an observation of a non-Hodgkinien primitive lymphoma of the thyroid, developed on Hashimoto's thyroiditis. The 61 years old woman was operated on a total thyroidectomy for a multinodular goiter with dysphagia. The non-Hodgkinien high-grade lymphoma infiltrated the perithyroidal tissues. The extension' assessment was negative and the lymphoma was classified stage IE. The treatment was supplemented by 6 cures of standard chemotherapy CEOP. Based on this observation and on a literature' review, we will discuss the clinical and therapeutic characteristics of this thyroid cancer.