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Novel therapies for diabetic kidney disease.

The number of people diagnosed with diabetes is rising throughout the world, which in turn drives upward the global frequency of diabetic kidney disease (DKD). Individuals with DKD are at an increased risk for premature death, cardiovascular disease, and other severe illnesses that result in frequent hospitalizations and increased health-care utilization. Current treatments concentrate on controlling hyperglycemia and hypertension with the specific use of renin-angiotensin system inhibitors. Although such measures reduce the risk of progressive kidney disease, DKD remains the leading cause of

Advances in the management of pediatric pulmonary hypertension.

Pulmonary hypertension is a rare disease in neonates, infants, and children, and is associated with substantial morbidity and mortality. An adequate understanding of the controlling pathophysiologic mechanisms is lacking. Moreover, a minority of research is focused specifically on neonatal and pediatric populations. Although therapeutic options have increased over the past several decades, they remain limited. In advanced pulmonary hypertension, progressive pulmonary vascular functional and structural changes ultimately cause increased pulmonary vascular impedance, right-ventricular failure, a

[Evidence-based therapy of Raynaud's syndrome].

Raynaud's syndrome has a prevalence of 3-5% in the general population. Despite its high frequency, the majority of available therapies have not been validated in randomized controlled trials. Effective therapies with a high level of evidence include the calcium channel blocker nifedipine. As analyzed by meta-analyses, nifedipine showed improvement of the peripheral circulation, as well as reduction of both the intensity and frequency of attacks in patients with primary and secondary Raynaud's syndrome as compared to placebo. Similar results in a metaanalysis were obtained for intravenous infus

[Study on the effect of Xiaoqinglong decoction on vascular endothelin inpulmonary hypertension rat based on Jiebiaokuoluo method].

OBJECTIVE: To discuss the effect of Xiaoqinglong decoction on vascular endothelin (ET) in rats pulmonary hypertension (PAH) model based on t … nd the PAH model group were given equal volumes of normal saline; the positive drug group was given bosentan (100 mg/kg); Xiaoqinglong decoction 15, 10 and 5 g/kg was given, respectively, in the high, medium and low dose groups; once daily for 30 days. The mean pulmonary artery pressure (mPAP) and right ventricle systolic pressure (RVSP) were then measured …

Pulmonary hypertension in left heart disease.

Pulmonary hypertension (PH) is a frequent complication of left heart disease arising from a wide range of cardiac disorders. In the clinical classification, PH associated with left heart disease is classified as Group 2, which includes left heart systolic dysfunction, left heart diastolic dysfunction and left heart valvular disease. In the past, rheumatic mitral valve disease was the most common cause of PH in left heart disease; however, today it is more likely to be associated with hypertensive and/or ischaemic heart disease. As the incidence of these conditions is increasing, the number of

[Treatment of idiopathic pulmonary arterial hypertension].

BACKGROUND: In the past 5-10 years, drug treatment of idiopathic pulmonary arterial hypertension has evolved considerably. Experience and results from use of such updated treatment in Norway has not been reported. MATERIAL AND METHOD: 32 patients newly diagnosed with idiopathic pulmonary arterial hypertension, were consecutively assessed with respect to hemodynamics and physical capacity. The results after three months were compared with those after 12 months. Observed survival was compared with estimated survival from the time when only conventional treatment was available. RESULTS: The pat

Ongoing clinical trials and treatment options for patients with systemic sclerosis-associated interstitial lung disease.

SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available. CYC is included in treatment guidelines, but it has limited efficacy and is associated with toxicity. MMF is becoming the most commonly used medication in clinical practice in North America and the UK, but its use is not universal. Newer agents targeting the pathogenic mechanisms underlying SSc

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… (BUILD-2 [ 34 ]) | 12-month randomized, double-blind, placebo-controlled trial | Bosentan 125 mg twice a day; placebo | 163 | Change in 6MWD at 12 months | No significant difference in 6MWD change between treatment arms at month 12 (bosentan −12 months, placebo +9 months) FVC and DLCO remained stable … Patients were randomized to the ET-1 receptor antagonist bosentan (62.5 mg twice a day, increasing to 125 mg twice a day after 4 weeks) or placebo. …

Role of endothelins on lymphocyte accumulation in allergic pleurisy.

Endothelins participate in different aspects of inflammatory reactions, including edema formation and eosinophil accumulation in allergic reaction. In this study, we demonstrated a role for endogenous endothelins in eosinophil and T lymphocyte recruitment and cytokine secretion in a murine model of allergic inflammation. Intrathoracic stimulation with endothelin-1 triggered a neutrophil accumulation at 4 h, concomitant with an increase of CD4+ and CD8+ T lymphocyte populations. Antigen challenge in sensitized animals leads to an increase in eosinophil and mononuclear cell numbers at 24 h. Trea

Characteristics of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis and Anticentriole Autoantibodies.

Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly d

Effects of a rehabilitation program on skeletal muscle function in idiopathic pulmonary arterial hypertension.

INTRODUCTION: A majority of patients with idiopathic pulmonary arterial hypertension (IPAH) display persistent exercise intolerance despite current therapies. Whether a rehabilitation program elicits favorable changes in muscle function which would partly explain improvements in exercise tolerance of IPAH patients remains unknown. We performed this study to assess the effect of a 12-week rehabilitation program on skeletal muscle characteristics and exercise tolerance in patients with IPAH. METHODS: Exercise capacity measured by the 6-minute walk test and by the cycle endurance test (CET), lim

Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial.

BACKGROUND: Infused and inhaled treprostinil are effective for treatment of pulmonary arterial hypertension (PAH), although their administration routes have limitations. This study assessed the efficacy and safety of bid oral sustained-release treprostinil in the treatment of PAH with a concomitant endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor. METHODS: A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized to placebo or oral treprostinil. All patients were stable on background ERA, PDE-5 inhibitor, or

Platelet-derived growth factor inhibition--a new treatment of pulmonary hypertension in congenital diaphragmatic hernia?

Increased pulmonary vascular resistance causing pulmonary artery hypertension is a major problem in the treatment of congenital diaphragmatic hernia with a strong association to mortality. We here report a patient with intractable pulmonary hypertension at 4 weeks of age unresponsive to conventional treatment. After administration of the platelet-derived growth factor (PDGF) receptor antagonist imatinib, pulmonary artery pressure gradually decreased to acceptable levels and the patient's clinical condition gradually improved.

Neurogenic inflammation in the context of migraine.

Despite considerable research into the pathogenesis of idiopathic headaches, such as migraine, the pathophysiological mechanisms underlying them remain poorly understood. Although it is well established that the trigeminal nerve becomes activated during migraine, the consequences of this activation remain controversial. One theory, based on preclinical observations, is that activation of trigeminal sensory fibers leads to a painful neurogenic inflammation within the meningeal (dural) vasculature mediated by neuropeptide release from trigeminal sensory fibres and characterized by plasma protein

Pharmacological inactivation of the endothelin type A receptor in the early chick embryo: a model of mispatterning of the branchial arch derivatives.

In the present study, we have applied an antagonist treatment to the chick embryo in ovo in order to demonstrate and dissect the essential roles of the endothelin type A (ETA) receptor in the embryonic development. We have cloned, sequenced and expressed the cDNA of the chick ETA receptor and shown that its affinity for endothelin antagonists is very similar to that shown by its mammalian counterparts. We have studied the spatio-temporal expression pattern of this receptor by in situ hybridization and shown that there is a high level of its mRNA within the mesenchyme of the branchial arches at

Efficacy of phosphodiesterase type 5 inhibitors in univentricular congenital heart disease: the SV-INHIBITION study design.

AIMS: In univentricular hearts, selective lung vasodilators such as phosphodiesterase type 5 (PDE5) inhibitors would decrease pulmonary resistance and improve exercise tolerance. However, the level of evidence for the use of PDE5 inhibitors in patients with a single ventricle (SV) remains limited. We present the SV-INHIBITION study rationale, design, and methods. METHODS AND RESULTS: The SV-INHIBITION trial is a nationwide multicentre, randomized, double blind, placebo-controlled, Phase III study, aiming to evaluate the efficacy of sildenafil on the ventilatory efficiency during exercise, in

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… The effect of bosentan in patients with a failing Fontan circulation. Cardiol Young 2009; 19: 331–339. 6. Mori H, Park IS, Yamagishi H, Nakamura M, Ishikawa S, Takigiku K, Yasukochi S, Nakayama T, Saji T, Nakanishi T. … Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial. Eur J Heart Fail 2013; 15: 690–698. 27. …

Drug repurposing-a promising approach for patients with angina but non-obstructive coronary artery disease (ANOCA).

In today's era of individualized precision medicine drug repurposing represents a promising approach to offer patients fast access to novel treatments. Apart from drug repurposing in cancer treatments, cardiovascular pharmacology is another attractive field for this approach. Patients with angina pectoris without obstructive coronary artery disease (ANOCA) report refractory angina despite standard medications in up to 40% of cases. Drug repurposing also appears to be an auspicious option for this indication. From a pathophysiological point of view ANOCA patients frequently suffer from vasomoto

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… Apart from the awaited results of the PRIZE trial, there are already a few published case reports demonstrating a good therapeutic response to bosentan in patients with coronary spasm ( 51 – 53 ). … A new hope in the treatment of coronary vasospasm: bosentan. Turk Kardiyol Dern Ars. (2013) 41(7):633–7. 10.5543/tkda.2013.37998 52. Vermeltfoort IAC, Raijmakers PGHM, Kamphuisen PW. Improved myocardial perfusion preceding clinical response on bosentan treatment for coronary vasospasm. …

Assessing two methods of repair of duodenal defects, jejunal serosal patch and jejunal pedicled flap, (an experimental animal study).

A large proportion of patients with congenital heart disease (CHD), in particular those with relevant systemic-to-pulmonary shunts, will dev … ort- and long-term outcomes of treatment with the orally active dual endothelin receptor antagonist bosentan in patients with Eisenmenger's syndrome. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation are options for Eisenmenger's syndrome patients with a poor prognosis. A treatment algorithm based on the one used …