Alterations in microbiota and fermentation products in equine large intestine in response to dietary variation and intestinal disease.

We aimed to determine the effects of variations in dietary composition on equine gut microbiota and their fermentation products, and proposed that dietary modifications profoundly affect microbial ecosystems and their metabolites. Bacterial communities within the large intestine of three groups of horses were compared using oligonucleotide-RNA hybridisation methodology. Each group consisting of six horses was maintained on (1) a grass-only diet, (2) a concentrate diet (i.e. supplemented with hydrolysable carbohydrates) and (3) a concentrate diet but horses were affected by simple colonic obstruction and distension (SCOD), a prevalent form of dietary-induced intestinal disease. We show that in response to dietary change and intestinal disease, there is a progressive and significant increase in Lachnospiraceae, the Bacteroidetes assemblage and the lactic acid-producing, Bacillus-Lactobacillus-Streptococcus (BLS) group. In contrast, there is a corresponding decrease in the proportion of obligate fibrolytic, acid-intolerant bacteria, Fibrobacter and Ruminococcaceae. Assessment of monocarboxylic acids indicated that there are significantly higher concentrations of lactic acid in the colonic contents of horses maintained on a concentrate diet and those suffering from SCOD, correlating with the observed increase in the population abundance of the BLS group. However, the population size of the Veillonellaceae (lactate utilisers) remained constant in each study group. The inability of this group to respond to increased lactic acid may be a contributory factor to the build-up of lactic acid observed in horses fed a concentrate diet and those suffering from SCOD

Alterations in microbiota and fermentation products in equine large intestine in response to dietary variation and intestinal disease.

We aimed to determine the effects of variations in dietary composition on equine gut microbiota and their fermentation products, and proposed that dietary modifications profoundly affect microbial ecosystems and their metabolites. Bacterial communities within the large intestine of three groups of horses were compared using oligonucleotide-RNA hybridisation methodology. Each group consisting of six horses was maintained on (1) a grass-only diet, (2) a concentrate diet (i.e. supplemented with hydrolysable carbohydrates) and (3) a concentrate diet but horses were affected by simple colonic obstruction and distension (SCOD), a prevalent form of dietary-induced intestinal disease. We show that in response to dietary change and intestinal disease, there is a progressive and significant increase in Lachnospiraceae, the Bacteroidetes assemblage and the lactic acid-producing, Bacillus-Lactobacillus-Streptococcus (BLS) group. In contrast, there is a corresponding decrease in the proportion of obligate fibrolytic, acid-intolerant bacteria, Fibrobacter and Ruminococcaceae. Assessment of monocarboxylic acids indicated that there are significantly higher concentrations of lactic acid in the colonic contents of horses maintained on a concentrate diet and those suffering from SCOD, correlating with the observed increase in the population abundance of the BLS group. However, the population size of the Veillonellaceae (lactate utilisers) remained constant in each study group. The inability of this group to respond to increased lactic acid may be a contributory factor to the build-up of lactic acid observed in horses fed a concentrate diet and those suffering from SCOD

Mechanisms of vascular damage in systemic sclerosis

Although being classified as autoimmune connective tissue disease, dominant components of the pathophysiology of systemic sclerosis (SSc) consists of mechanisms of vascular damage, which can occur early in the course of the disease. Amongst them are abnormal vasoreactivity, hypoxia, insufficient neoangiogenesis and direct damage of vascular and perivascular cells. They result in a decreased capillary blood flow, and subsequently in clinically overt symptoms such as Raynaud's syndrome and fingertip ulcers. In addition, in active disease vascular pathology can affect various other organs, predominantly the lung, the kidney, the heart but also the gastrointestinal tract. Vascular pathology contributes also significantly to overall morbidity and mortality in SSc patients and reduces life expectancy by at least a decade. Fortunately, molecular biology has revealed a number of underlying pathways on the cellular and subcellular levels, including key factors of the aberrant function of (peri)vascular cells and autoimmune effector cells, the dysregulation of vasoconstrictive molecules and their receptors, the upregulation of intracellular signaling kinases and the altered balance of hypoxia-induced vascular growth factors. This increasing knowledge of vascular pathology in SSc has also resulted in novel therapeutic approaches ranging from endothelin antagonists to application of progenitor cells to counteract this aberrant vascular pathology and to support the repair of the dysfunctional vasculature

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified