Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.     

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.     

Extracardiac Direct Total Cavopulmonary Connection

We report a successful extracardiac direct total cavopulmonary connection without prosthetic materials performed in a 3-year-old boy with tricuspid atresia, infundibular pulmonary stenosis, and normally positioned great arteries. The transected pulmonary trunk was bought down posterolaterally with respect to the right atrium and was anastomosed end-to-end with the inferior vena cava.     

Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats

In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammutory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4g/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutroph il infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact ruts. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.     

ASO Visual Abstract: Influence of Damaged Stomach on Anastomotic Leakage After Cervical Esophagogastrostomy for Patients with Esophageal Cancer

Annals of Surgical Oncology -     

Effects of dorzolamide hydrochloride on ocular tissues.

We studied the intraocular pharmacokinetics of dorzolamide hydrochloride eye drops and the effect of dorzolamide on carbonic anhydrase activity and localization in ocular tissues. Carbonic anhydrase activity was detected in normal ocular tissues. The activity was inhibited in corneal endothelial cells, the ciliary body, lens epithelial cells, or the retina 1 to 8 hours after instillation of dorzolamide eye drops. In lens epithelial cells and the retina, the enzyme activity had not recovered even 10 hours after instillation of the drug. Immunostaining did not reveal any differences between the group administered dorzolamide eye drops and the control group administered a physiologically balanced solution. Time-related changes in dorzolamide concentrations in ocular tissues were measured by high-performance liquid chromatography (HPLC). In the cornea, anterior aqueous, iris, ciliary body and retina, drug concentrations increased 15 minutes after the instillation and peaked within 1 hour. These results suggest that dorzolamide immediately suppresses carbonic anhydrase activity in ocular tissues, and is rapidly distributed among the tissues of the eye when administered as eye drops.     

Development of Innovative Contra-angle Handpiece Device with Piston Movement for Root Canal Preparation

IntroductionThe purpose of this study was to assess the optimal amplitude and weight of the newly developed contra-angle handpiece. The handpiece uses piston movement without using an endodontic motor and enables a safe, quick, and reliable canal preparation.MethodsA prototype handpiece was designed. Instrumentation was performed on root canal resin blocks by 20 operators in 3 groups: the prototype handpiece with an H file (a stainless steel #25 manual H file, the piston group), a manually standardized technique with a K file (stainless steel #15–25 K files, the manual group), and a nickel-titanium (NiTi) reciprocating file with an endodontic motor (Reciproc Blue R25 [VDW, Munich, Germany], the NiTi group). Transportation of the canal center line and the time required for preparation were measured and statistically analyzed.ResultsThe optimal condition was an amplitude of 1.35 mm and a weight of 61.0 g. Transportation of the canal center was observed in all groups. A statistically significant difference was found at 2.0–3.0 mm from the apical foramen between the piston or NiTi group and the manual group, but no significant difference was found between the piston and NiTi groups. The least transportation was found in the NiTi and piston groups. The handpiece with a #25 H file demonstrated a good centering ability, similar to the NiTi file, which enabled speedy preparation. The time required for preparation between the piston or NiTi group and the manual group was statistically different. No significant difference was observed between the piston and NiTi groups (P < .05).ConclusionsWe concluded that the newly designed handpiece achieved efficient canal preparation and negotiation. The handpiece could avoid endodontic accidents, including ledge formation, instrument separation, and perforation.     

Steroid pulse therapy in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). Clinical symptoms of SFTS often involve encephalopathy and other central neurological symptoms, particularly in seriously ill patients; however, pathogenesis of encephalopathy by SFTSV is largely unknown. Herein, we present case reports of three patients with SFTS, complicated by encephalopathy, admitted to Tokushima University hospital: one patient was a 63-year-old man, while the other two were 83- and 86-year-old women. All of them developed disturbance of consciousness around the 7th day post onset of fever. After methylprednisolone pulse therapy of 500 mg/day, all of them recovered without any neurological sequelae. SFTSV genome was not detected in the cerebrospinal fluid of 2 out of the 3 patients that were available for examination. In these patients, disturbance of consciousness seemed to be an indirect effect of the cytokine storm triggered by SFTSV infection. We propose that short-term glucocorticoid therapy might be beneficial in the treatment of encephalopathy during early phase of SFTSV infection.     

Clinical characteristics of influenza virus-induced lower respiratory infection during the 2015 to 2016 season

Background

Influenza A(H1N1)pdm09 virus infections often manifest severe respiratory symptoms, particularly in patients with a past history of allergic disease. Most of these findings were reported during the 2009 pandemic. The purpose of this study was to detail the clinical characteristics of influenza virus-induced lower respiratory infection (LRI) during the A(H1N1)pdm09-predominant 2015–2016 season.

Self-assembly of photoresponsive azo-containing phospholipids with a polar group as the tail

Vesicles or micelles prepared from amphiphiles with azobenzene (Az) moieties and long alkyl chains have attracted much attention in drug delivery systems. To induce release behavior from smart carriers via trans–cis photoisomerization of the Az groups, UV light exposure is typically used, but it can damage DNA and hardly penetrates cells. In this paper, Az-containing phospholipids without long alkyl tails were designed and synthesized; in these compounds, the end group of the Az moiety was substituted with a –NO₂ and –OCH₃ group (abbreviated N6 and M6, respectively). N6 self-assembled into H-aggregates with an interdigitated bilayered structure in water through the antiparallel orientation due to π–π interactions of the Az group, the attractive van der Waals forces, and the interactions and bending behavior of the phosphocholine groups. Vesicles showing visible light stimuli-responsive behavior were obtained by mixing N6 and M6, and the release of encapsulated calcein was triggered by visible light.

A mixture of a nitro- and methoxy-substituted azo-containing phospholipids without long alkyl tails formed vesicles showing visible light stimuli-responsive behavior. Release of encapsulated calcein from the vesicles was triggered by visible light.