Effects of ProstagIand in F2a on the Spontaneous Contractions and Electrical Activities in the Circular Smooth MuscIe of the Guinea-Pig Stomach

Effects of PGF2a and indomethacin on the mechanical and electrical membrane properties of guinea-pig antral smooth muscle were studied using microeletrodes and tension recording technique and whole cell patch clamp technique. In this tissue, indomethacin inhibited the contractility and such an effect was reversed by PGF2a. PGF2a increased spontaneous contractions potently and the frequency and amplitudes of slow waves were also enhanced. PGF2a-induced contractions were not abolished by the pretreatment with nifedipine or by the nominal Ca2+-free condition but were abolished by pretreatment with La3+ or absolute Ca2+-free condition. Ionic currents were also measured by whole cell voltage clamp technique. PGF2a increased the size of voltage operated Ca2+ inward currents, and Ca-dependent K+ outward currents, but had no effect on sustained outward currents. From the above results, it is assumed that PGF2 a acts as an endogenous prostaglandin in the gastric antrum of the guinea-pig. PGF2a has promoting effects on electrical activities and such effects seem to contribute to the increase of contraction, but the greatest part of the increase of contraction is due to receptor-mediated increase of [Ca2+]i. Several possible mechanisms were suggested for the receptor-mediated [Ca2+]i increase

Choice of recipient vessels in muscle-sparing transverse rectus abdominis myocutaneous flap breast reconstruction: A comparative study

Background Thoracodorsal vessels (TDVs) and internal mammary vessels (IMVs) have both been widely employed as recipient vessels for use in free muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps. However, whether TDVs or IMVs are preferable as recipient vessels for autologous breast reconstruction with a free MS-TRAM flap remains controversial. The purpose of this study was to compare the clinical outcomes when TDVs were used as recipient vessels to those obtained when IMVs were used as recipient vessels for autologous breast reconstruction with a free MS-TRAM flap. Methods A retrospective matched-cohort study was performed. We retrospectively reviewed data collected from patients who underwent a free MS-TRAM flap for autologous breast reconstructions after mastectomy between March 2003 and June 2013. After a one-to-one matching using age, 100 autologous breast reconstructions were selected in this study. Of the 100 breast reconstructions, 50 flaps were anastomosed to TDVs and 50 to IMVs. Patient demographics and clinical outcomes including operation time, length of hospital stay, postoperative complications, and aesthetic score were compared between the two groups. Results No statistically significant differences were found between the two groups in patient demographics and clinical outcomes, including the complication rates and aesthetic scores. There were no major complications such as total or partial flap loss in either group. Conclusions The results of our study demonstrate that both TDVs and IMVs were safe and efficient as recipient vessels in terms of the complication rates and aesthetic outcomes

Helical tomotherapy with concurrent capecitabine for the treatment of inoperable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Helical tomotherapy, an advanced intensity-modulated radiation therapy with integrated CT imaging, permits highly conformal irradiation with sparing of normal tissue. Capecitabine, a pro-drug of 5-FU that induces thymidine phosphorylase can achieve higher levels of intracellular 5-FU when administered concurrently with radiation. We evaluated the feasibility as well as the clinical outcome of concurrent administration of capecitabine with tomotherapy in patients with advanced pancreatic cancer.</p> <p>Methods</p> <p>Nineteen patients with advanced pancreatic cancer including primarily unresectable disease and recurrence after curative surgery were included in the study. Two planning target volumes (PTV) were entered: PTV1 is gross tumor volume; and PTV2, the volume of the draining lymph nodes. The total doses to target 1 and target 2 were 55 and 50 Gy, respectively. Capecitabine at 1600 mg/m²/day was administered on each day of irradiation.</p> <p>Results</p> <p>Twenty six measurable lesions were evaluated. Overall in-field response rate was 42.3%; partial responses were achieved in 53.3% of the pancreatic masses, 28.6% of distant metastatic lesions and 25.0% of regional lymph nodes. The median duration of follow-up after tomotherapy was 6.5 months. None of the lesions showed in-field progression. Treatment was well tolerated with only minor toxicities such as grade 1 nausea (one patient), grade 1 hand-foot syndrome (one patient) and grade 1/2 fatigue (three patients).</p> <p>Conclusions</p> <p>Helical tomotherapy with concurrent capecitabine is a feasible option without significant toxicities in patients with advanced pancreatic cancer. We achieved excellent conformal distribution of radiation doses and minimal treatment-related toxicities with promising target volume responses.</p

The Impact of Intima-media Thickness of Radial Artery on Early Failure of Radiocephalic Arteriovenous Fistula in Hemodialysis Patients

This study was performed to investigate the impact of intima-media thickness (IMT) of radial artery on early failure of radiocephalic arteriovenous fistula (AVF) in hemodialysis (HD) patients. Ninety uremic patients undergoing radiocephalic AVF operation were included in this study. During the operation, 10-mm long partial arterial walls were removed with elliptical form for microscopic analysis. Specimens were stained with trichrome and examined by a pathologist blinded to the clinical data. And then AVF patency was followed up for 1 yr after the operation. Of the total 90 patients, 31 patients (34%) had AVF failure within 1 yr after the operation. Mean IMT was thicker in failed group (n=31) than in patent group (n=59) (486±130 µm vs. 398±130 µm, p=0.004). The AVF patency rate within 1 yr after the operation was lower in patients with IMT ≥500 µm (n=26) than in patients with IMT <500 µm (n=64) (p=0.017). Age was an independent risk factor of IMT. Diabetes mellitus tended to be independent risk factor but not statistically significant. Our data suggest that increased radial artery IMT is closely associated with early failure of radiocephalic AVF in HD patients

Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates.

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing

Endoscopic Pancreatic Sphincterotomy: Indications and Complications

Background/Aims: Although a few recent studies have reported the effectiveness of endoscopic pancreatic sphincterotomy (EPST), none has compared physicians' skills and complications resulting from the procedure. Thus, we examined the indications, complications, and safety of EPST performed by a single physician at a single center. Methods: Among 2,313 patients who underwent endoscopic retrograde cholangiopancreatography between January 1996 and March 2008, 46 patients who underwent EPST were included in this retrospective study. We examined the indications, complications, safety, and effectiveness of EPST, as well as the need for a pancreatic drainage procedure and the concomitant application of EPST and endoscopic sphincterotomy (EST). Results: Diagnostic indications for EPST were chronic pancreatitis (26 cases), pancreatic divisum (4 cases), and pancreatic cancer (8 cases). Therapeutic indications for EPST were removal of a pancreaticolith (10 cases), stent insertion for pancreatic duct stenosis (9 cases), nasopancreatic drainage (7 cases), and treatment of sphincter of Oddi dysfunction (1 case). The success rate of EPST was 95.7% (44/46). Acute complications of EPST included five cases (10.9%) of pancreatitis and one of cholangitis (2.2%). EPST with EST did not reduce biliary complications. Endoscopic pancreatic drainage procedures following EPST did not reduce pancreatic complications. Conclusions: EPST showed a low incidence of complications and a high rate of treatment success; thus, EPST is a relatively safe procedure that can be used to treat pancreatic diseases. Pancreatic drainage procedures and additional EST following EPST did not reduce the incidence of procedure-related complications

Crossed Cerebellar Diaschisis in Cerebral Infarction: Correlation of SPECT and Clinical Features

Patients with supratentorial cerebral infarction frequently show depressed metabolic activity in the contralateral cerebellar hemisphere which is known as crossed cerebellar diaschtsisfCt.D). In order to investigate the relationship between this phenomenon and the characteristics of the supratentorial lesion, we retrospectively evaluated the findings of 99mTc-HMPAO single photon emission computed tomography(SPECT) in 26 patients with a single supratentorial infarction lesion. A cerebellar asymmetry index (AIcbll), percent difference between both cerebellar hemispherestzx'Scbll],SPECT volume deficit (SVD), and magnetic resonance volume deficit (MVD) were quantitated. A CCD, defined as AIcbll >12%, was observed in 12 of the 26 patients (46.2%). No correlation was found between the ~%cbll and duration of disease, SVD, or MVD. SVD and MVD values showed no significant difference between CCD positive and negative groups (71+47ml \IS. 70+68ml and 90+84ml \IS. 67+77ml, respectively). Patients with frontoparietal lobe or deep middle cerebral artery territory infarctions showed a significantly higher incidence of CCD and lower ~%cbll values. Patients with severe hemiparesis had a higher incidence of CCD and lower ~%cbll values than those with milder or no hemiparesis (incidence, 5/5 \IS. 6/18, p=0.008; ~ %cbll,-21. 4+3.8% \IS -8. 3±11. 1%, p=O. 014). None of the 12 patients with CCD showed clinical signs of cerebellar dysfunction. In conclusion, the location rather than the extent of the lesion appears to be the major determinant for the occurrence and magnitude of CCD in stroke patients

Comparison of Early and Late Conversion of Sirolimus in Experimental Model of Chronic Cyclosporine Nephropathy

Sirolimus (SRL) is a promising drug for replacing calcineurin inhibitors. We performed this study to determine the optimal time of conversion from cyclosporine (CsA) to SRL in an experimental model of chronic CsA nephropathy. Three separate studies were performed. In the first study, SRL was given to rats with or without CsA for 4 weeks. In the second study, rats were treated initially with CsA for 1 week, and then switched to SRL (early conversion). In the third study, CsA was given for 4 weeks and then replaced by SRL for 4 weeks treatment of CsA (late conversion). The influence of SRL on CsA-induced renal injury was evaluated by assessing renal function, histopathology (interstitial inflammation and fibrosis), and apoptotic cell death. Combined CsA and SRL treatment significantly impaired renal function, increased apoptosis, and interstitial fibrosis and inflammation compared with CsA or SRL treatment alone. Early conversion to SRL did not change renal function, histopathology, or apoptosis compared with early CsA withdrawal. By contrast, late conversion to SRL significantly aggravated these parameters compared with late CsA withdrawal. In conclusion, early conversion from CsA to SRL is effective in preventing CsA-induced renal injury in a setting of CsA-induced renal injury

β-Glucan enhanced apoptosis in human colon cancer cells SNU-C4

The apoptotic effect of bacteria-derived β-glucan was investigated in human colon cancer cells SNU-C4 using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcription-polymerase chain reaction (RT-PCR) expressions of Bcl-2, Bax, and Caspase-3 genes, and assay of caspase-3 enzyme activity. β-Glucan of 10, 50, and 100 µg/mL decreased cell viability in a dose-dependent manner with typical apoptotic characteristics, such as morphological changes of chromatin condensation and apoptotic body formation from TUNEL assay. In addition, β-glucan (100 µg/mL) decreased the expression of Bcl-2 by 0.6 times, whereas the expression of Bax and Caspase-3 were increased by 3.1 and 2.3 times, respectively, compared to untreated control group. Furthermore, the caspase-3 activity in the β-glucan-treated group was significantly increased compared to those in control group (P < 0.05). Bacterial derived β-glucan could be used as an effective compound inducing apoptosis in human colon cancer