Formulation of novel dry powder inhalation for fluticasone propionate and salmeterol xinafoate with capsule-based device.

The aim of this study was to develop a novel fluticasone propionate (FP) and salmeterol xinafoate (SX)-loaded dry powder inhaler (DPI) system, which was composed of powder formulation and performance. The air flow resistances were determined with various types of DPI device, showing that the modified RS01 device gave the specific resistance similar to the commercial DPI device. The particle properties of FP, SX, and inhalation grade lactose particles, such as particle size, size distribution, and fine content, were assessed. Subsequently, the aerodynamic behaviors of the DPI powder formulations were evaluated by the in vitro deposition of drugs in the DPI products using Andersen cascade impactor. Amongst the DPI powder formulations tested, the formulation composed of FP, SX, Respitose® SV003, Respitose® SV010, and Respitose® ML006 at the weight ratio of 0.5/0.145/19/19/2 gave depositions, emitted dose, fine particle dose, fine particle fraction, and mass median aerodynamic diameter of drugs similar to the commercial product, suggesting that they had similar aerodynamic behaviors. Furthermore, it gave excellent content uniformity. Thus, this DPI using the modified RS01 device would be recommended as a candidate for FP and SX-loaded pharmaceutical DPI products.

Risk Factors of On-Pump Conversion during Off-Pump Coronary Artery Bypass Graft.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCABG) procedures can avoid the complications of an on-pump bypass. However, some cases unexpectedly require conversion to cardiopulmonary bypass during OPCABG. The risk factors associated with a sudden need for cardiopulmonary bypass were analyzed. METHODS: This retrospective study included 283 subjects scheduled for OPCABG from 2001 to 2010. These were divided into an OPCABG group and an on-pump conversion group. Preoperative, operative, and postoperative variables were compared between the 2 groups. RESULTS: Of the 283 patients scheduled for OPCABG, 47 (16%) were switched to on-pump coronary artery bypass grafting (CABG). The mortality of the both the OPCABG and on-pump conversion groups was not significantly different. The major risk factors for conversion to on-pump CABG were congestive heart failure (CHF) (odds ratio [OR], 3.5; p=0.029), ejection fraction (EF) <35% (OR, 4.4; p=0.012), and preoperative beta-blocker (BB) administration (OR, 0.3; p=0.007). The use of intraoperative (p=0.007) and postoperative (p=0.021) inotropics was significantly higher in the conversion group. The amount of postoperative drainage (p<0.001) and transfusion (p<0.001) also was significantly higher in the conversion group. There were no significant differences in stroke or cardiovascular complications between the groups over the course of short-term and long-term follow-up. CONCLUSION: Patients who undergo OPCABG and have CHF or a lower EF (<35%) are more likely to undergo on-pump conversion, while preoperative BB administration could help prevent conversions from OPCABG to on-pump CABG.

Novel dabigatran etexilate hemisuccinate-loaded polycap: Physicochemical characterisation and in vivo evaluation in beagle dogs.

The purpose of this study was to develop a novel dabigatran etexilate hemisuccinate (DEH) salt-loaded polycap with bioequivalence to the dabigatran etexilate mesylate (DEM)-loaded commercial product. DEH prepared with dabigatran etexilate base (DE) and succinic acid was less hygroscopic but less soluble than DEM. Numerous micronized DEHs and DEH-loaded solid dispersions were prepared employing the spiral jet-milling and spray-drying techniques, respectively. Among the formulations prepared, a micronized DEH prepared with the injection air at 1.5bar and the grinding air at 2bar, and a DEH-loaded solid dispersion prepared with 6g HPMC most improved the drug solubility, respectively. Moreover, the micronized DEH provided more increased drug solubility and dissolution compared with the solid dispersion, even though its drug solubility was still lower than that of DEM. Unlike the situation in other studies, the enhanced solubility and dissolution of DEH was more due to particle size reduction than to a change to the amorphous form. The micronized DEH prepared with Myrj 52S had greater drug solubility than preparations with other surfactants. Among the organic acids investigated, only fumaric acid (128.8mg) showed a similar pattern in pH changes to the DEM-loaded commercial product. Furthermore, in order to make the environment acidic while preventing the direct contact of the drug with fumaric acid, the polycap was composed of a tablet containing the micronized DEH, Myrj 52S and other ingredients, and separate fumaric acid. This micronized DEH-loaded polycap was dissolution- and bio-equivalent to the DEM-loaded commercial product in beagle dogs. Thus, the novel micronized DEH-loaded polycap would be a promising alternative to the DEM-loaded commercial product.

Clinical Effect of Left Ventricular Dysfunction in Patients with Mitral Stenosis after Mitral Valve Replacement.

BACKGROUND: Mitral stenosis (MS) remains one of the important heart diseases. There are many factors that influence the clinical outcomes, and little is known about how left ventricular (LV) dysfunction clinically affects the prognosis of the patient with MS after mitral valve replacement (MVR). We reviewed our clinical experiences of MVR in patients with MS who had LV dysfunction. METHODS: Between January 1991 and January 2013, 110 patients with MS who underwent MVR were analyzed and divided into two groups according to ejection fraction (EF). Group 1 (EF≤45%) included 13 patients and group 2 (EF>45%) included 97 patients. RESULTS: Thromboembolism occurred in 8 patients after MVR (group 1: n=3, 23.1%; group 2: n=5, 5.2%) and its incidence was significantly higher in group 1 than in group 2 (p=0.014). There were 3 deaths each in groups 1 and 2 during follow-up. The overall rate of cardiac-related death in group 1 was significantly higher than in group 2 (group 1: n=3, 23.1%; group 2: n=3, 3.1%; p=0.007). The cumulative survival rate at 1 and 15 years was 83.9% and 69.9% in group 1 and 97.9% and 96.3% in group 2 (p=0.004). The Cox regression analysis revealed that survival was significantly associated with postoperative stroke (p=0.011, odds ratio=10.304). CONCLUSION: This study identified postoperative stroke as an adverse prognostic factor in patients with MS after MVR, and as more prevalent in patients with LV dysfunction. Postoperative stroke should be reduced to improve clinical outcomes for patients. Preventive care should be made in multiple ways, such as management of LV dysfunction, atrial fibrillation, and anticoagulation.

Development of novel prasugrel base microsphere-loaded tablet with enhanced stability: Physicochemical characterization and in vivo evaluation in beagle dogs.

The objective of this study was to develop a novel prasugrel base microsphere-loaded tablet (PBMST) with enhanced stability as a bioequivalent to the commercial prasugrel hydrochloride-loaded tablet. Numerous prasugrel base-loaded microspheres were prepared with hydroxypropylmethyl cellulose (HPMC), colloidal silica and various acidifying agents using a spray-drying process, and the physicochemical properties, solubility and stability were investigated. The PBMSTs were prepared and their dissolution, pharmacokinetics in beagle dogs and stability were evaluated compared to commercial prasugrel hydrochloride-loaded tablets. Among the acidifying agents tested, phosphoric acid provided the greatest increase in drug solubility, by as much as 110-fold. The prasugrel base-loaded microspheres composed of prasugrel base, HPMC, colloidal silica and phosphoric acid at a weight ratio of 10/10/5/2.5 provided an amorphous drug and reduced particle size of about 11.3µm. Moreover, it exhibited excellent solubility and improved stability compared to prasugrel base and hydrochloride. Moreover, PBMST drug dissolution was improved in comparison to the prasugrel base-loaded tablet (PBT), with similar dissolution to the commercial prasugrel hydrochloride-loaded tablet at pH 1.2 and 4.0. PBMST provided significantly higher plasma concentrations of AUC and Cmax in beagle dogs compared to PBT. In particular, the AUC of PBMST was approximately four times greater than PBT, leading to improved oral bioavailability. There were no significant differences observed for all pharmacokinetic parameters between PBMST and the commercial prasugrel hydrochloride-loaded tablet, suggesting their bioequivalence in beagle dogs. Furthermore, the prepared PBMSTs were stable for at least six months. Therefore, this novel prasugrel base microsphere-loaded tablet could be a potential alternative for enhancing the stability and bioavailability of prasugrel.

Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor.

The purpose of this study was to develop HM30181 mesylate salt (HM30181M)-loaded microcapsules as a novel P-glycoprotein inhibitor for enhancing the oral absorption of paclitaxel. The effect of various carriers including hydrophilic polymers and solvents on the solubility of HM30181M were evaluated. Among the hydrophilic polymers and solvents tested, HPMC and methylene chloride (and ethanol) provided the highest HM30181M solubility. Numerous HM30181M-loaded microcapsules were prepared with HPMC, silicon dioxide and acidifying agents using a spray-drying technique, and their solubility, dissolution and physicochemical properties were evaluated. Furthermore, a pharmacokinetic study was performed after oral administration of paclitaxel alone, simultaneously with HM30181M powder or HM30181M-loaded microcapsules to rats. Among the acidifying agents investigated, phosphoric acid provided the best improvement in the solubility and dissolution of HM30181M. Moreover, the microcapsule composed of HM30181M, HPMC, silicon dioxide and phosphoric acid at a weight ratio of 3:6:3:2 remarkably enhanced the solubility and dissolution of HM30181M compared with the HM30181M powder alone. The microcapsules were spherical in shape, had a reduced particle size of about 7µm, and contained HM30181M in an amorphous state. Furthermore, this microcapsule significantly enhanced HM30181M absorption, making it about 1.7-fold faster and 1.6-fold greater after simultaneous administration, leading to about 70- and 2-fold improved oral bioavailability of paclitaxel compared with paclitaxel alone and the simultaneous administration with HM30181M powder, respectively. Thus, this novel microcapsule could be a potential candidate for effective P-glycoprotein inhibition during oral administration of paclitaxel.

Effect of magnesium carbonate on the solubility, dissolution and oral bioavailability of fenofibric acid powder as an alkalising solubilizer.

To investigate the possibility of developing a novel oral pharmaceutical product using fenofibric acid instead of choline fenofibrate, the powder properties, solubility, dissolution and pharmacokinetics in rats of fenofibrate, choline fenofibrate and fenofibric acid were compared. Furthermore, the effect of magnesium carbonate, an alkalising agent on the solubility, dissolution and oral bioavailability of fenofibric acid was assessed, a mixture of fenofibric acid and magnesium carbonate being prepared by simple blending at a weight ratio of 2/1. The three fenofibrate derivatives showed different particle sizes and melting points with similar crystalline shape. Fenofibric acid had a significantly higher aqueous solubility and dissolution than fenofibrate, but significantly lower solubility and dissolution than choline fenofibrate. However, the fenofibric acid/magnesium carbonate mixture greatly improved the solubility and dissolution of fenofibric acid with an enhancement to levels similar with those for choline fenofibrate. Fenofibric acid gave lower plasma concentrations, AUC and Cmax values compared to choline fenofibrate in rats. However, the mixture resulted in plasma concentrations, AUC and Cmax values levels not significantly different from those for choline fenofibrate. Specifically, magnesium carbonate increased the aqueous solubility, dissolution and bioavailability of fenofibric acid by about 7.5-, 4- and 1.6-fold, respectively. Thus, the mixture of fenofibric acid and magnesium carbonate at the weight ratio of 2/1 might be a candidate for an oral pharmaceutical product with improved oral bioavailability.

Novel montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats.

To develop a montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats, several montelukast sodium-loaded suspensions were prepared with a suspending agent, stabilizers and anti-aggregation agents, and their stabilities were investigated by visually observing the sedimentation phenomenon and determining the concentration of the degradation product. Moreover, dissolution and pharmacokinetic studies of the optimized formulation were examined in rats compared to commercial montelukast sodium-loaded granules. Avicel RC-591 (Avicel), a suspending agent, prevented the sedimentation of these suspensions at >2.496 (w/v) per cent composition. Amongst the stabilizers tested, fumaric acid provided the lowest concentration of montelukast sulphoxide (a degradation product) in these suspensions at 40 °C, demonstrating its excellent stabilizing activity. Furthermore, as an anti-aggregation agent, glycerin gave lower amounts of degradation product than those with poloxamer 407 and Tween 80. In particular, montelukast-loaded oral suspension, an aqueous suspension containing montelukast sodium/Avicel/fumaric acid/glycerin at a concentration of 312/2496/15.6/62.4 (mg/100 ml), and the commercial granules exhibited similar dissolution profiles in 0.5% (w/v) aqueous solution of sodium lauryl sulphate. Moreover, the pharmacokinetics in rats provided by this suspension was comparable to that of the commercial granules, suggesting that they were bioequivalent. In addition, it was physically and chemically stable at 40 °C for at least 6 months. Thus, this montelukast sodium-loaded oral suspension, with bioequivalence to the commercial granules and excellent stability, could be a prospective dosage form for the treatment of asthma.

Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells.

Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling. [BMB Reports 2016; 49(4): 220-225].

A Rare Cause of Secondary Hypertension in A Young Adult.

Reninoma is a rare, renin-secreting, benign renal neoplasm that can cause secondary hypertension. We report a case of a 21-year-old man who suffered from progressively worsening headache for 2 months with a history of hypertension for 7 years. Laboratory studies showed normal potassium level, increased basal plasma renin activity, and normal serum aldosterone level. Abdominal computed tomography and magnetic resonance imaging revealed a small mass in the middle region of the right kidney. Partial nephrectomy was performed; immunohistochemical results demonstrated typical features of reninoma. Postoperatively, blood pressure and potassium level were normal at the 2-month follow-up.

Novel fenofibric acid-loaded controlled release pellet bioequivalent to choline fenofibrate-loaded commercial product in beagle dogs.

The objective of this study was to develop a novel fenofibric acid-loaded controlled release pellet showing enhanced, or equivalent to, bioavailability compared with two commercially available products containing fenofibrate or choline fenofibrate. The effect of solubilizing agents on drug solubility and the impact of fillers on core properties were investigated. Among them, magnesium carbonate most improved drug solubility, and κ-carrageenan provided the best spherical cores. The fenofibric acid-loaded pellet was prepared with magnesium carbonate and κ-carrageenan employing the extrusion/spheronizing technique followed by coating with ethylcellulose. Furthermore, dissolution and pharmacokinetic study in beagle dogs were performed compared to the fenofibrate-loaded commercial tablet (FCT) and choline fenofibrate-loaded commercial mini-tablet (CFCM). This fenofibric acid-loaded pellet showed controlled release of the drug in phosphate buffer (pH 6.8) and 0.025 M sodium laurylsulfate within 4h. Furthermore, this pellet and CFCM exhibited similar dissolution profiles. Plasma concentrations greater than 1,000 ng/ml were maintained from 30 min to 8h, suggesting a sustained release pattern. Also, the fenofibric acid-loaded pellet gave significantly higher AUC and Cmax values than FCT, indicating that it improved the bioavailability of fenofibrate due to enhanced solubility and sustained release. In addition, this pellet and CFCM were not significantly different in terms of pharmacokinetic parameters including AUC, Cmax and Tmax. Thus, this pellet was bioequivalent to CFCM in beagle dogs. In conclusion, this fenofibric acid-loaded controlled release pellet would be a potential alternative to the choline fenofibrate-loaded commercial product.

Enhanced oral bioavailability of paclitaxel by solid dispersion granulation.

The main objective of this study was to develop novel orally administrable tablets containing solid dispersion granules (SDG) of amorphous paclitaxel (PTX) prepared by fluid bed technology, and to evaluate its in vitro dissolution and in vivo pharmacokinetics (PK) in beagle dogs. The SDG were prepared using optimized composition by fluid bed technology, and characterized for solid-state properties. The release study of SDG tablet (SDG-T) in simulated gastric fluid showed a rapid release of PTX, reaching maximum dissolution within 20 min. Finally, the PK profile of SDG-T and a reference formulation Oraxol™ (oral solution formulation used in Phase I clinical study) at a dose of 60 mg orally with co-administration of P-gp inhibitor HM38101, and Taxol® at a dose of 10 mg intravenously (i.v.) was investigated in beagle dogs. The mean absolute BA% of PTX following SDG-T and Oraxol™ solution was 8.23 and 6.22% in comparison to i.v. administration of Taxol®. The relative BA% of PTX from SDG-T in comparison to Oraxol™ solution was 132.25% at a dose of 60 mg following oral administration. In conclusion, we have successfully prepared PTX tablets with solid dispersion granules (SDG) of amorphous PTX using fluid bed technology that could provide plasma PTX concentration in the range of 10-150 ng/mL for a period of 24 h following oral administration in dogs with a P-gp inhibitor. Hence, this could be a promising formulation for PTX oral delivery and could be used in our intended clinical studies following pre-clinical efficacy studies.

Development of a novel bi-coated combination capsule containing mosapride and probiotics for irritable bowel syndrome.

The objective of this study was to develop a novel combination product containing mosapride and probiotics for the treatment of irritable bowel syndrome. Enteric-coated hard gelatin capsules containing probiotics were prepared to protect acid-labile probiotics from the stomach by spray coating with hydroxypropylmethylcellulose phthalate, and then coated with various hydrophilic polymer solutions containing mosapride. The influence of different hydrophilic polymers on the aqueous solubility and dissolution of sparingly soluble mosapride from the capsule was investigated to select the one which imparted highest solubility to mosapride in an aqueous solution. The physicochemical properties of the hydrophilic polymer coating were assessed using SEM and DSC. In addition, the bioavailability of the mosapride-coated capsule in beagle dog was evaluated and compared to that of conventional mosapride tablet (CMT). Based on DSC studies, the mosapride in polymer coating underwent amorphization or molecular dispersion. The enteric-capsule coated with mosapride/HPMC exhibited improved solubility of mosapride at acidic pH and showed significantly improved AUC (1.5-fold) and Cmax (1.6-fold) compared to the CMT. In conclusion, drug/polymer coated enteric gelatin capsule can be an alternative technique for co-delivery of sparingly water-soluble drug and acid-labile drug for enhanced solubility and bioavailability as well as for protection from acid degradation.

Ginsenoside fractions regulate the action of monocytes and their differentiation into dendritic cells.

BACKGROUND: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosides-the major active components of ginseng-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). METHODS: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on CD14(+) monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect CD4(+) T cell activity. RESULTS: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-α production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes. We confirmed that DCs derived from CD14(+) monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-γ) production by CD4(+) T cells with the coculture of Gin-DCs with CD4+ T cells. CONCLUSION: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate CD4(+) T cells.

Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet.

The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-ß-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule.

Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation.

AIM: The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS). METHODS: Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated. RESULTS: The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127 ± 0.020 g, 98.25 ± 2.50%, 2.5 ± 0.08 kg and 9 ± 1.0 min, respectively. The release of sildenafil from the SVS was more than 90% at 30 min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n = 0.464). The plasma PK study demonstrated a significantly lower Cmax (∼10 times) and AUC0-24 h (∼13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher Cmax (∼40 times) and AUC0-24 h (∼20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution. CONCLUSION: This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.

A case of right sinus of valsalva rupture with dissection into interventricular septum causing left ventricular outflow tract obstruction.

Sinus of Valsalva aneurysm (SVA) is an uncommon anomaly of the aorta. Rupture of SVA often precipitates dramatic clinical complications, including heart failures. Right SVAs are the most common type, and when they rupture, they usually rupture into the right ventricle or right atrium. Rupture into left ventricle or interventricular septum is rare. Herein, we report a case of right SVA rupture with dissection into interventricular septum, which produced significant left ventricular outflow tract obstruction and aortic regurgitation. The case was successfully treated by surgical operation.

Left atrial myxoma presenting with unusual cystic form.

Cardiac myxomas are the most common primary benign tumors of uncertain etiology. They usually present as polypoid or oval-shaped masses projecting into a heart chamber from the interatrial septum and have a soft, gelatinous consistency without a cystic structure. We report a case of left atrial myxoma with a single cystic form.

Zanamivir oral delivery: enhanced plasma and lung bioavailability in rats.

The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol(®), sodium cholate, sodium caprate, hydroxypropyl ß-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and Papp of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the AUC0-24 h of ZMR in the lungs following oral administration of PO-SC was 125.22 ± 27.25 ng hr ml(-1) with a Cmax of 156.00 ± 24.00 ng/ml reached at 0.50±0.00 h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the IC50 concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.

Outcomes of Mitral Valve Repair: Quadrangular Resection versus Chordal Replacement.

BACKGROUND: Mitral valve repair for posterior mitral leaflet (PML) prolapse has been considered to be a standard treatment because of its high success rate and high level of patient satisfaction. The aim of this study was to evaluate the clinical results of two different techniques of PML prolapse, quadrangular resection (QR) and chordal replacement (CR). MATERIALS AND METHODS: The subjects consisted of 56 patients who had undergone mitral valve repair for PML prolapse between November 1997 and December 2010. The patients were divided into two groups according to surgical technique. Among them, 31 patients underwent QR (group QR) and 25 patients had CR (group CR). We reviewed the medical records of the patients retrospectively to compare the clinical outcomes of both groups. RESULTS: After mitral valve repair, the degree of mitral regurgitation (MR) in both groups decreased to the to a mild degree or less and the amount of remnant MR was slightly higher in the CR group but it was not statistically different. Three patients received mitral valve-related reoperation (2 in the QR group and 1 in the CR group). Freedom from mitral valve-related reoperation at 7 years was 93% for the QR group and 96% for the CR group and was not significantly different between the two groups. CONCLUSION: Both QR and CR showed excellent long-term results and were considered equally effective methods for PML prolapse.