Isosorbide Di-(Linoleate/Oleate) Stimulates Prodifferentiation Gene Expression to Restore the Epidermal Barrier and Improve Skin Hydration.

The breakdown of the epidermal barrier and consequent loss of skin hydration is a feature of skin aging and eczematous dermatitis. Few treatments, however, resolve these underlying processes to provide full symptomatic relief. In this study, we evaluated isosorbide di-(linoleate/oleate) (IDL), which was generated by esterifying isosorbide with sunflower fatty acids. Topical effects of IDL in skin were compared with those of ethyl linoleate/oleate, which has previously been shown to improve skin barrier function. Both IDL and ethyl linoleate/oleate downregulated inflammatory gene expression, but IDL more effectively upregulated the expression of genes associated with keratinocyte differentiation (e.g., KRT1, GRHL2, SPRR4). Consistent with this, IDL increased the abundance of epidermal barrier proteins (FLG and involucrin) and prevented cytokine-mediated stratum corneum degradation. IDL also downregulated the expression of unhealthy skin signature genes linked to the loss of epidermal homeostasis and uniquely repressed an IFN-inducible coexpression module activated in multiple skin diseases, including psoriasis. In a double-blind, placebo-controlled trial enrolling females with dry skin, 2% IDL lotion applied over 2 weeks significantly improved skin hydration and decreased transepidermal water loss (NCT04253704). These results demonstrate mechanisms by which IDL improves skin hydration and epidermal barrier function, supporting IDL as an effective intervention for the treatment of xerotic pruritic skin.

Computer-based formulation design and optimization using Hansen solubility parameters to enhance the delivery of ibuprofen through the skin.

Trial-and-error approach to formulation development is long and costly. With growing time and cost pressures in the pharmaceutical industry, the need for computer-based formulation design is greater than ever. In this project, emulgels were designed and optimized using Formulating for Efficacy™ (FFE) for the topical delivery of ibuprofen. FFE helped select penetration enhancers, design and optimize emulgels and simulate skin penetration studies. pH, viscosity, spreadability, droplet size and stability of emulgels were evaluated. Franz cell studies were performed to test in vitro drug release on regenerated cellulose membrane, drug permeation in vitro on Strat-M® membrane and ex vivo on porcine ear skin, a marketed ibuprofen gel served as control. Emulgels had skin compatible pH, viscosity and spreadability comparable to a marketed emulgel, were opaque and stable at 25 °C for 6 months. Oleyl alcohol (OA), combined with either dimethyl isosorbide (DMI) or diethylene glycol monoethyl ether (DGME) provided the highest permeation in 24 h in vitro, which was significantly higher than the marketed product (p < 0.01). OA + DGME significantly outperformed OA ex vivo (p < 0.05). The computer predictions, in vitro and ex vivo penetration results correlated well. FFE was a fast, valuable and reliable tool for aiding in topical product design for ibuprofen.

Prevention of contrast-induced nephropathy by adequate hydration combined with isosorbide dinitrate for patients with renal insufficiency and congestive heart failure.

BACKGROUND: Adequate hydration remains the mainstay of contrast-induced nephropathy prevention, and nitrates could reduce cardiac preload. HYPOTHESIS: This study aimed to explore the adequate hydration with nitrates for patients with chronic kidney disease (CKD) and congestive heart failure (CHF) to reduce the risk of contrast-induced nephropathy (CIN) and at the same time avoid the acute heart failure. METHODS: Three hundred and ninty-four consecutive patients with CKD and CHF undergoing coronary procedures were randomized to either adequate hydration with nitrates (n = 196) or to routine hydration (control group; n = 198). The adequate hydration group received continuous intravenous infusion of isosorbide dinitrate combined with intravenous infusion of isotonic saline at a rate of 1.5 mL/kg/h during perioperative period. The definition of CIN was a 25% or 0.5 mg/dL rise in serum creatinine over baseline. This trial is registered with www.clinicaltrials.gov, number NCT02718521. RESULTS: Baseline characteristics were well-matched between the two groups. CIN occurred less frequently in adequate hydration group than the control group (12.8% vs 21.2%; P = 0.018). The incidence of acute heart failure did not differ between the two groups (8 [4.08%] vs 6[3.03%]; P = 0.599). Cumulative major adverse events (death, myocardial infarction, stoke, hospitalization for acute heart failure) during the 90-day follow-up were lower in the adequate hydration with nitrates group (P = 0.002). CONCLUSIONS: Adequate hydration with nitrates can safely and effectively reduce the risk of CIN in patients with CKD and CHF.

Isosorbide and nifedipine for Chagas' megaesophagus: A systematic review and meta-analysis.

BACKGROUND: Chagas disease is a neglected tropical disease. About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders, including megaesophagus. Treatment focuses on improving symptoms, and isosorbide and nifedipine may be used for this purpose. METHODOLOGY: We conducted a systematic review to evaluate the effectiveness of pharmacological treatment for Chagas' megaesophagus. We searched MEDLINE, Embase and LILACS databases up to January 2018. We included both observational studies and RCTs evaluating the effects of isosorbide or nifedipine in adult patients with Chagas' megaesophagus. Two reviewers screened titles and abstracts, selected eligible studies and extracted data. We assessed the risk of bias using NIH 'Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group' and RoB 2.0 tool. Overall quality of evidence was assessed using GRADE. PRINCIPAL FINDINGS: We included eight studies (four crossover RCTs, four before-after studies). Three studies evaluated the effect of isosorbide on lower esophageal sphincter pressure (LESP), showing a significant reduction (mean difference -10.52mmHg, 95%CI -13.57 to-7.47, very low quality of evidence). Three studies reported the effect of isosorbide on esophageal emptying, showing a decrease in esophageal retention rates (mean difference -22.16%, 95%CI -29.94 to -14.38, low quality of evidence). In one study, patients on isosorbide reported improvement in the frequency and severity of dysphagia (moderate quality of evidence). Studies evaluating nifedipine observed a decrease in LESP but no effect on esophageal emptying (very low and low quality of evidence, respectively). Isosorbide had a higher incidence of headache as a side effect than nifedipine. CONCLUSIONS: Although limited, available evidence shows that both isosorbide and nifedipine are effective in reducing esophageal symptoms. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile. TRIAL REGISTRATION: PROSPERO CRD42017055143. ClinicalTrials.gov CRD42017055143.

Retarder action of isosorbide in a microemulsion for a targeted delivery of ceramide NP into the stratum corneum.

Ceramide [NP] is an integral component of the stratum corneum (SC) lipid matrix and is capable of forming tough and stable lamellar structures. It was proven, that in skin diseases as psoriasis or atopic dermatitis different ceramide (CER) classes, including [NP], are degraded. It is obvious that topically application of CER on impaired skin is useful for repairing the skin barrier but a tendency for low penetration due to its poor solubility in conventional dosage forms was observed. Therefore, a stable and physiologic compatible colloidal carrier system, a microemulsion (ME), was developed and characterized. The increasing knowledge of the new colloidal systems in this last decade shows their benefits in dermal application. Isosorbide (Polysorb P) was incorporated into the ME developed. It was expected that Polysorb P has a retarder potential in order to accumulate the CER in the SC, the outermost layer of the skin. Thereby the CER [NP] would be able to interact with the affected skin layers to strengthen the skin barrier. The release and penetration behavior of the CER [NP] from the ME was assessed ex vivo in a Franz diffusion cell. The results of the study showed that CER [NP] penetrate largely in the upper layers of the skin (from SC to stratum basale), which was the desired region. A recovery in the acceptor could not be detected that underlines an accumulation in upper layers. Furthermore, significantly increased values for the SC for the ME with retarder were not received. No differences in the concentrations of CER [NP] were observed. However, the toxicity of MEs was investigated using hens egg test chorioallantoic membrane (HET-CAM). For the isosorbide-containing ME no difference was obtained in comparison to the non-containing. The results showed that both MEs are safe to be used on the skin for the controlled penetration of CER [NP] into the skin. The isosorbide had no effect on the irritating effect as well as on the penetration of the used CER.

An outbreak of pyrimethamine toxicity in patients with ischaemic heart disease in Pakistan.

We investigated an outbreak of darkening of skin, bleeding from multiple sites, leucopenia and thrombocytopenia in ischaemic heart disease patients. Case patients were defined as patients who had received medicines from the pharmacy of Punjab Institute of Cardiology between 1 December 2011 and 12 January 2012 and who developed any one of the following: darkening of skin, bleeding from any site, thrombocytopenia and leucopenia. Clinical and drug-related data were abstracted. All 664 case patients had received iso-sorbide-mono-nitrate contaminated with about 50 mg of pyrimethamine, and 151 (23%) died. The median age of 117 patients admitted at Jinnah Hospital Lahore was 57 years (range, 37-100) and 92 (79%) were male. The median time from intake of medicine to presentation was 37 days (range 13-72). Symptoms and signs included bleeding (in 95% of the patients), skin hyperpigmentation (in 61%), diarrhoea (in 53%) and abdominal pain (in 48%). At presentation, the median white cell count was 2.3 × 10(9) /L (range, 0.1 × 10(9) -16.0 × 10(9) ), the median hemoglobin concentration was 109 g/L (range 58-169) and the median platelet count was 18 × 10(9) /L (range, 0 × 10(9) -318 × 10(9) ). Bone marrow examination revealed trileneage dysplasia and severe megaloblastosis. The predictors of mortality included presentation prior to 15 January 2012, age more than 57 years, hypotension and leukocyte count less than 1.5 × 10(9) /L. None of the patients who died received Calcium folinate because all deaths occurred prior to contaminant identification. We describe an outbreak of pyrimethamine toxicity in ischaemic heart disease patients receiving medicines from a single pharmacy due to accidental contamination of iso-sorbide mono-nitrate tablets at industrial level. Late recognition of illness resulted in high mortality.

Effects of oral isosorbide and glycerol on intraocular pressure, serum osmolality, and blood glucose in normal dogs.

OBJECTIVE: To evaluate and compare the effects of oral isosorbide and glycerol on intraocular pressure (IOP), serum osmolality (SOSM), and blood glucose (BG) in normal dogs. METHODS: Ten normal dogs were administered an oral dose of either isosorbide (1.5 g/kg), glycerol (1.5g/kg) or control (water, 2 mL/kg) in a double blind protocol. Prior to dosing, baseline IOP, SOSM, and BG were measured in all dogs. IOP was subsequently evaluated every 30 min for 6h post-dosing. BG and SOSM were reassessed at times 1, 2, 4, and 6h post-dosing. After 1-week washout periods, every dog was subject to each of the three treatments. The dogs were held NPO for 4h after dosing. RESULTS: The maximal decrease in IOP was 17% by 1h and 13.5% by 30min after glycerol and isosorbide administration, respectively. However, the overall changes in IOP were not significant when compared to the controls. SOSM increased above baseline after dosing with glycerol but decreased after isosorbide, which difference was significant at 1, 2, and 4 h post-administration. BG significantly increased after administration of glycerol relative to the control but was not significantly affected by isosorbide. CONCLUSIONS: Neither glycerol nor isosorbide significantly affected IOP when compared to the control. However, glycerol induced significant elevations in both BG relative to the control and SOSM relative to isosorbide.

Trial of Chinese medicine Wu-Ling-San for acute low-tone hearing loss.

PURPOSE: We used new criteria to elucidate the demographics of acute low-tone sensorineural hearing loss (ALHL) and tested the Chinese medicine Wu-Ling-San as a treatment for ALHL. PROCEDURES: We reviewed the medical records of patients with ALHL seen at the outpatient clinic of the Social Insurance Central General Hospital in Tokyo from April 2006 through August 2011. Patients were treated with an oral steroid, a diuretic, or Wu-Ling-San; alone or in combination. RESULTS: We identified 130 definite and 48 probable ALHL cases. The mean age and male-to-female ratio in probable cases were significantly higher than those in definite cases (p < 0.05). The steroid-Wu-Ling-San combination was significantly more effective (100% recovery) than the diuretic alone (59%), Wu-Ling-San alone (62%), or the steroid-diuretic combination (60%, p < 0.05). CONCLUSIONS: ALHL can develop in older patients more frequently than we expected. The steroid-Wu-Ling-San combination is a possible new treatment for ALHL.

Randomized controlled trial of the efficacy of isosorbide-SR addition to current treatment in medical expulsive therapy for ureteral calculi.

It has been suggested that nitrates are potent smooth muscle relaxants that may reduce pain and facilitate ureteral stone passage; therefore it may be an option for medical expulsive therapy in ureteral stones. In a prospective randomized controlled clinical trial, we evaluated the efficacy of medical expulsive therapy with isosorbide-SR 40 mg in patients with ureteral stones (≤10 mm). The patients with ureteral stones in KUB or urinary tract ultrasonography were randomized to receive methylprednisolone plus celecoxib without (control group), and with isosorbide-SR 40 mg (treatment group) for 21 days. 66 patients [33(50%) in control, 33(50%) in treatment group] were entered randomly to our study. The stone expulsion rate was not significantly different between two groups (54.5 vs. 45.5%) (P = 0.497). The need for surgical procedures were more common in control group within 21 days (9.4 vs. 6.1%) and more common in treatment group after 21 days (33.3 vs. 21.9%) (P = 0.756).Patients in the treatment group experienced more intractable pain (27.3 vs. 6.1%), intractable vomiting (3 vs. 0%) (P = 0.046) and hospitalization (3 vs. 0%) (P = 0.314). Drug side effects including headache and dizziness were more common in treatment group (39.4 vs. 9.1%) (P = 0.004). In our study, the use of isosorbide-SR in treatment group did not improve the stone expulsion rate in patients with ureteral stones (≤10 mm) but developed more side effects. Then it may not an appropriate alternative for medical expulsive therapy. Of course, further trials are recommended.

Endolymphatic hydrops and therapeutic effects are visualized in 'atypical' Meniere's disease.

A 53-year-old male with fluctuating low frequency sensorineural hearing loss and tinnitus, but without vertigo, was evaluated by MRI obtained by intratympanic injection of a gadolinium-based contrast agent (GBCA) before and after the administration of isosorbide. The endolymphatic hydrops was semi-quantitatively evaluated by a 3.0-T MR scanner. For quantification, the affected side/contralateral side ratios were calculated. A gadodiamide (a kind of GBCA)-enhanced space surrounding the endolymph in the affected side with a 0.50 ratio (which may have represented endolymphatic hydrops) improved after isosorbide therapy to a 0.98 ratio. Thus, endolymphatic hydrops was demonstrated in a patient with 'atypical' Meniere's disease (MD), suggesting that at least some atypical MD may share similar etiology with, and therefore be a continuum of, MD. Also, therapeutic effects could be visualized by using MRI. Therefore, MRI-based diagnosis of MD-related disease will be a powerful tool not only because of its precision but also its usefulness for therapeutic evaluation.

Endolymphatic hydrops as a cause of audio-vestibular manifestations in relapsing polychondritis.

Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant -SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP -- including the inner ear dysfunction -- were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.

[Usefulness of sublingual isosorbide to assess the reversibility of pulmonary hypertension in cardiac transplant candidates]. / Utilidad de isosorbide sublingual en la reversibilidad de la hipertensión pulmonar reactiva, en pacientes candidatos a trasplante cardíaco.

BACKGROUND: Continuous infusion of short life vasodilators are employed to test reversibility of pulmonary hypertension in cardiac transplant candidates. Sublingual isosorbide administration has not been described in the literature and it might be a simpler alternative. AIM: To evaluate sublingual isosorbide administration as a test of reversibility of pulmonary hypertension in heart failure. PATIENTS AND METHODS: Prospective evaluation of patients referred for cardiac transplant evaluation. Patients underwent right catheterization for hemodynamic measurements at baseline and after repeated doses of 5 mg sublingual isosorbide every 5 minutes until observing a decrease in pulmonary vascular resistance decrease or symptomatic hypotension. RESULTS: Twenty one patients, 18 men, age 49+/-15 years, were studied. Fourteen (66%) were transplanted. The mean sublingual isosorbide dose was 15+/-5 mg. After isosorbide administration, there was a significant decrease in mean arterial pressure (80+/-8.5 to 71+/-6.6 mmHg, p <0.0001), mean pulmonary artery pressure (38+/-11 to 26+/-7.8 mmHg, p <0.0001), systemic vascular resistance (1540+/-376 to 1277+/-332 dyn*s/cm5 p <0.001), pulmonary vascular resistance (3.5+/-2.2 to 2,5+/-1.6 Wood Units, p <0.05) and transpulmonary gradient (13+/-7 a 10+/-4 mmHg, p <0.004). The cardiac output increased from 3.96+/-0.7 to 4.38+/-0.9 L/min, p=0.05. The relation between pulmonary and systemic vascular resistance before and after isosorbide was 0.17 and 0.15, respectively (p=0.04). One transplanted patient with partial reversibility of pulmonary hypertension developed acute right heart failure. CONCLUSIONS: Sublingual isosorbide administration is useful and well tolerated to evaluate the reversibility of pulmonary hypertension prior cardiac transplant.

Coronary artery spasm and the polymorphisms of the endothelial nitric oxide synthase gene.

BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of vasospastic angina, and contributes to the development of several acute coronary syndromes. Endothelial nitric oxide synthase (ecNOS) catalyzes the synthesis of nitric oxide, which regulates vascular tone, and may be related to coronary vasospasm. The present study investigated whether coronary spasm is related to particular polymorphisms of the ecNOS gene. METHODS AND RESULTS: Spasm provocation by serial infusions of acetylcholine was performed on 165 patients who were clinically suspected of having angina. In both study patients and healthy controls (n=400), genomic polymorphisms of the ecNOS gene were determined by using polymerase chain reaction. Quantitative luminal diameter measurements of the 3 major coronary arteries were initially obtained before and after acetylcholine injection, and then after isosorbide dinitrate injection, by using a computer-assisted analysis system. Logistic multiple regression analysis identified the a/a or a/b genotype in intron 4 of ecNOS (NOS4a: p=0.0431, odds ratio (OR) 2.43) and diabetes mellitus (p=0.0060, OR 4.88) as significant predictors of coronary spasm. In the patients with NOS4a, both the induced and spontaneous contractions were augmented. CONCLUSION: The present study results indicated that NOS4a could be a good marker for coronary artery spasm.

Utilidad de isosorbide sublingual en la reversibilidad de la hipertensión pulmonar reactiva, en pacientes candidatos a trasplante cardíaco / Usefulness of sublingual isosorbide to assess the reversibility of pulmonary hypertension in cardiac transplant candidates

Background: Continuous infusion of short life vasodilators are employed to test reversibility of pulmonary hypertension in cardiac transplant candidates. Sublingual isosorbide administration has not been described in the literature and it might be a simpler alternative. Aim: To evaluate sublingual isosorbide administration as a test of reversibility of pulmonary hypertension in heart failure. Patients and Methods: Prospective evaluation of patients referred for cardiac transplant evaluation. Patients underwent right catheterization for hemodynamic measurements at baseline and after repeated doses of 5 mg sublingual isosorbide every 5 minutes until observing a decrease in pulmonary vascular resistance decrease or symptomatic hypotension. Results: Twenty one patients, 18 men, age 49±15 years, were studied. Fourteen (66%) were transplanted. The mean sublingual isosorbide dose was 15±5 mg. After isosorbide administration, there was a significant decrease in mean arterial pressure (80±8.5 to 71±6.6 mmHg, p <0.0001), mean pulmonary artery pressure (38±11 to 26±7.8 mmHg, p <0.0001), systemic vascular resistance (1540±376 to 1277±332 dyn*s/cm5 p <0.001), pulmonary vascular resistance (3.5±2.2 to 2,5±1.6 Wood Units, p <0.05) and transpulmonary gradient (13±7 a 10±4 mmHg, p <0.004). The cardiac output increased from 3.96±0.7 to 4.38±0.9 L/min, p=0.05. The relation between pulmonary and systemic vascular resistance before and after isosorbide was 0.17 and 0.15, respectively (p=0.04). One transplanted patient with partial reversibility of pulmonary hypertension developed acute right heart failure. Conclusions: Sublingual isosorbide administration is useful and well tolerated to evaluate the reversibility of pulmonary hypertension prior cardiac transplant.

Papel de los nitratos en el tratamiento de la enfermedad cardiovascular / Role of nitrates in the treatment of cardiovascular diseases

Los nitratos orgánicos, en sus diferentes presentaciones, han constituido uno de los pilares para el tratamiento de las enfermedades cardiovasculares durante más de 100 años. Los nitratos son donadores de óxido nítrico; por tanto, su efecto primordial es el de la relajación del músculo liso endotelial. Producen dilatación venosa y arterial, por lo que reducen la precarga y la poscarga. Sus principales indicaciones son el tratamiento sintomático de la angina de esfuerzo estable, el síndrome coronario agudo, y la insuficiencia cardíaca aguda y crónica. Asimismo, añadidos a la terapia convencional en pacientes afroamericanos con insuficiencia cardíaca crónica, en asociación con la hidralazina, producen una reducción de la mortalidad. Su papel actual en pacientes de otras razas aún se desconoce. La principal limitación de esta terapia es el desarrollo de tolerancia, que conduce a la atenuación de los efectos farmacológicos antiisquémicos, antianginosos y hemodinámicos con la utilización continuada. En la práctica clínica, lo más conveniente para reducir al mínimo la tolerancia es utilizar la menor dosis necesaria y dejar un intervalo libre de nitratos, para permitir la recuperación del endotelio (AU)

For more than 100 years, organic nitrates, in one form or another, have formed one the central pillars of the treatment of cardiovascular disease. As nitrates are nitric oxide donors, their main effect is to induce endothelial smooth muscle relaxation. Nitrates induce both venous and arterial dilatation, thereby reducing both preload and afterload. They are principally indicated for the symptomatic treatment of stable angina, acute coronary syndromes, and acute and chronic heart failure. Moreover, nitrates also reduce mortality in Afro-americans when given with hydralazine as an addition to conventional therapy. Their role in other ethnic groups is unknown. The main limitation of nitrate therapy is that its continued use leads to the development of tolerance, with reductions in anti-ischemic and hemodynamic effects. Clinically, the most appropriate way of minimizing tolerance is to use the lowest acceptable dose and to introduce nitrate-free periods to enable recovery of the endothelium (AU)

Tratamiento médico de la insuficiencia cardiaca por disfunción sistólica / Treatment of heart failure due to systolic dysfunction

La insuficiencia cardiaca por disfunción sistólica hace referencia a un síndrome clínico caracterizado por signos y/o síntomas de insuficiencia cardiaca en el contexto de una enfermedad estructural cardiaca que provoca una disminución de la función contráctil del ventrículo izquierdo. En las guías de tratamiento actuales se insiste en la importancia del diagnóstico y el tratamiento de la disfunción ventricular izquierda sin síntomas de insuficiencia cardiaca. Se hace necesaria la implementación de la evidencia científica disponible en el tratamiento de todos los pacientes atendidos por esta enfermedad, desde el consejo dietético hasta los dispositivos más complejos. Desconocemos con exactitud la respuesta al tratamiento en subgrupos de pacientes infrarrepresentados en los grandes ensayos clínicos. Tras la reciente publicación de las guías europeas y americanas, en el presente capítulo se hace una revisión del tratamiento médico indicado en los pacientes con insuficiencia cardiaca por disfunción sistólica (AU)

Heart failure due to systolic dysfunction is a clinical syndrome that is characterized by the appearance of the signs or symptoms of heart failure in the presence of structural heart disease that has led to decreased left ventricular contractility. Current clinical practice guidelines emphasize the importance of diagnosing and treating left ventricular dysfunction in patients without symptoms of heart disease. It is essential that currently available scientific findings are taken into account when treating all patients seen with this condition, from dietary advice to use of the most sophisticated devices. We do not know the precise treatment responses of patient belonging to subgroups that were underrepresented in large clinical trials. The present article, written after the recent publication of European and American clinical practice guidelines, provides a summary of recommended medical treatment for patients with heart failure due to systolic dysfunction (AU)

Prevention of Variceal Bleeding and Measurement of Hepatic Vein Pressure Gradient / 대한간학회지

No abstract available.

Treatment of aphthous stomatitis with saturated potassium nitrate/dimethyl isosorbide.

Concentrated potassium nitrate has been used to lessen the pain caused by aphthous stomatitis. The problem with this approach is that it can have difficulty penetrating into the deeper layers of mucosae or skin, and for this reason, its beneficial affects are not routinely predictable. When dimethyl isosorbide is added to potassium nitrate in an aqueous hydroxyethyl cellulose gel, it enhances the capacity of potassium nitrate to more completely permeate these tissues and predictably promote rapid pain control and aphthae healing.