[A Trial of Practical Training on Online Medication Instructions in Clinical Preparatory Education: Development of Human Resources to Provide New Forms of Medical Care after the COVID-19 Pandemic].

The coronavirus disease 2019 (COVID-19) pandemic has considerably affected several social services. The Ministry of Health, Labour, and Welfare has partially revised the Pharmaceuticals and Medical Devices Law and established legislations on permanent online medication instructions. Based on these social needs, the development of human resources to provide online medication instructions is vital. Therefore, we developed a training program for providing online medication instructions in preparatory clinical education. Pharmacy students who had conducted medical interviews with standardized patients participated in the training. Educational outcomes were evaluated using an objective multiple-choice test and free description before and after practical training. The median number of correct answers on objective tests on the legislation on online medication instructions increased significantly. Based on the free description analysis, students were able to comprehend the influence of communication environment on the quality of medication instructions. Based on the results of the direct evaluation using objective testing and indirect evaluation by analyzing the free descriptions, they also acquired the skills necessary for providing online medication instructions. Therefore, this training program can contribute to mastering the provision of online medication instructions.

Comparison of the cost and outcomes following totally laparoscopic and laparoscopy-assisted distal gastrectomies for gastric cancer: a single-institution comparison.

OBJECTIVE: This study aimed to compare the short-term surgical outcomes and cost-benefits following totally laparoscopic distal gastrectomy (TLDG) and laparoscopy-assisted distal gastrectomy (LADG) for the treatment of gastric cancer. METHODS: Between April 2007 and December 2013, a total of 100 patients with gastric cancer underwent laparoscopic distal gastrectomy. The patients were classified into two groups according to whether intracorporeal anastomosis or extracorporeal anastomosis had been performed. The comparison between the groups was based on clinicopathological characteristics and surgical and economic outcomes. RESULTS: There were 57 and 43 patients who underwent TLDG and LADG, respectively. The patients' demographics and tumor characteristics did not show any statistically significant differences with the exception for tumor location. In the LADG group, tumors were localized to relatively higher positions (p = 0.024) and received Roux-en-Y reconstruction more frequently (p < 0.001). There were no differences in the incidence of morbidity. Anastomotic leakage was not recorded in either group, although anastomotic stenosis occurred in one patient (1.8 %) after TLDG and in two patients (4.7 %) after LADG. Compared with the LADG group, the TLDG group was associated with significantly less operative blood loss (p < 0.001), a shorter time to oral intake (p = 0.012), and hospital stay (p = 0.018). The median operation costs were greater in the TLDG group than in the LADG group (¥982,000 in TLDG vs. ¥879,830 in LADG; p < 0.001), whereas the median total hospital costs were similar between the two groups (¥1302,665 in LADG vs. ¥1383,322 in TLDG: p = 0.119). CONCLUSION: This study suggests that TLDG is as technically feasible, safe, and effective as LADG for treating patients with gastric cancer. Furthermore, TLDG is associated with equivalent total hospital costs compared with LADG. The increased operation cost is offset by the decreased costs associated with longer periods of hospitalization.

Laparoscopic gastrectomy for gastric cancer in the elderly patients.

BACKGROUND: This study aimed to investigate the short-term surgical outcomes of laparoscopic gastrectomy for gastric cancer in elderly patients in order to determine the safety, feasibility, and risk factors for postoperative complications associated with this procedure. METHODS: We retrospectively investigated 208 patients who underwent laparoscopic gastrectomy for gastric cancer between January 2007 and September 2014. After excluding 15 patients with unusual medical histories or surgical treatments, 193 were selected for this cohort study. We divided the patients into two cohorts: elderly patients (≥75 years old) and non-elderly patients (<74 years old). We compared these cohorts with respect to clinicopathological characteristics and intraoperative and postoperative parameters. RESULTS: The overall complication rates were 11.4% (8 of 70 patients) in the elderly cohort and 8.1% (10 of 123 patients) in the non-elderly cohort (P = 0.449). In a univariate analysis, Charlson comorbidity index (CCI) of ≥3, American Society of Anesthesiologists (ASA) score of 3, operative time of ≥330 min, and intraoperative blood loss of ≥50 ml were found to correlate significantly with postoperative complications. In a multivariate analysis, CCI of ≥3 (P = 0.034), ASA score of 3 (P = 0.019), and intraoperative blood loss of ≥50 ml (P = 0.016) were found to be independent risk factors of postoperative complications. In contrast, age was not found to significantly affect the risk of postoperative complications. CONCLUSIONS: Laparoscopic gastrectomy for gastric cancer can be successfully performed in elderly patients with an acceptable complication rate. This study suggested that high CCI, ASA score, and intraoperative blood loss volume were identified as independent predictors of postoperative complications after laparoscopic gastrectomy for gastric cancer.

Clinical significance of medial approach for suprapancreatic lymph node dissection during laparoscopic gastric cancer surgery.

OBJECTIVE: Suprapancreatic lymph node dissection is critical for gastric cancer surgery. Beginning in 2010, a medial approach was adopted for suprapancreatic lymph node dissection during laparoscopic gastrectomy for distal gastric cancer in our institution. The aim of this study was to compare surgical outcomes of the medial approach and conventional approach in laparoscopic gastric surgery. METHODS: Between January 2007 and December 2012, a total of 100 patients with clinical T1 or T2 tumors underwent laparoscopic distal gastrectomy involving suprapancreatic lymph node dissection by the medial approach (n = 44) and conventional approach (n = 56) with curative intent. The comparison was based on clinicopathological characteristics and surgical outcome. RESULTS: The laparoscopic procedure was not converted to laparotomy in any patient. The patients' demographics and tumor characteristics did not show any statistically significant difference, except for tumor location. In the conventional approach group, the tumors were at a higher position (p = 0.037) and more frequently received Roux-en-Y reconstruction (p < 0.001). Intracorporeal anastomosis was significantly more common in the medial approach group (p < 0.001). Compared with the conventional approach, the medial approach was associated with significantly less operative blood loss (p < 0.001), more retrieved suprapancreatic lymph nodes (p = 0.019), and a shorter hospital stay (p = 0.018). The rates of complications were comparable between the two groups. CONCLUSION: This study suggests that the medial approach to suprapancreatic lymph node dissection seems to be convenient and useful in laparoscopic gastric cancer surgery.

Expression, purification, and refolding of active recombinant human E-selectin lectin and EGF domains in Escherichia coli.

Attempts to obtain active E-selectin from Escherichia coli (E. coli) have not yet been successful. In this study, we succeeded in expressing the recombinant lectin and epidermal growth factor domain fragments of human E-selectin (rh-ESLE) in E. coli on a large-scale. The rh-ESLE protein was expressed as an inactive form in the inclusion bodies. The inactive form of rh-ESLE was denatured and solubilized by 6 M guanidine hydrochloride and then purified by Ni(2+) affinity chromatography under denaturing conditions. Denatured rh-ESLE was then refolded by a rapid-dilution method using a large amount of refolding buffer, which contained arginine and cysteine/cystine. The refolded rh-ESLE showed binding affinity for sLe(X) (K(d) = 321 nM, B(max) = 1.9 pmol/µg protein). This result suggests that the refolded rh-ESLE recovered its native and functional structure.

Lactate levels in the detection of preoperative bowel strangulation.

The aim of this retrospective study was to examine whether various laboratory parameters could predict viability of strangulation in patients with bowel obstruction. Forty patients diagnosed with bowel strangulation were included. We performed operations for all patients within 72 hours of the start of symptoms. Blood samples were obtained from all patients immediately before operation. Arterial blood was examined for pH and lactate levels using a blood gas analyzer. We also evaluated white blood cell count and serum levels of creatine phosphokinase, lactic dehydrogenase, amylase, and C-reactive protein. At surgery, 18 patients had viable strangulation and did not undergo resection, whereas 22 had nonviable strangulation and underwent resection of the necrotic bowel. None of the patients died. Bowel strangulation was caused most commonly by adhesions. In terms of diagnostic efficiency, lactate level was the only laboratory parameter significantly associated with viability (P < 0.01, Mann-Whitney test). Other laboratory data did not show statistically significant associations. These results suggest that arterial blood lactate level (2.0 mmol/L or greater) is a useful predictor of nonviable bowel strangulation.

Identification of a novel carbohydrate-mimicking octapeptide from chemical peptide library and characterization as selectin inhibitor.

We found a novel octapeptide (H-YRNWFGRW-NH2) mimicking sialyl Lewis X (sLe(X)) carbohydrate from a chemical peptide library with anti-sLe(X) monoclonal antibody (MAb) 2H5. The peptide libraries were constructed by Fmoc-based solid-phase methodology using the mix-split method. The octapeptide sequence was determined by the iterative deconvolution method using anti-sLe(X) MAb 2H5. To define the important residues for interaction with anti-sLe(X) MAb 2H5, alanine-scanning analogues of H-YRNWFGRW-NH2 were synthesized. Substitution of Tyr¹, Trp4, Arg7 and Trp8 to Ala resulted in a marked drop in affinity. This result indicates that aromatic and cationic amino residues have a key role in interacting with anti-sLe(X) MAb 2H5. The binding property of the octapeptide was evaluated with anti-sLe(X) MAb 2H5 and human E-selectin. The octapeptide showed high inhibitory potency (IC50=17.8 nM) for sLe(X) and competitively inhibited the binding of anti-sLe(X) MAb 2H5 in a dose-dependent manner. The octapeptide had high affinity (K(d)=0.168 µM) for E-selectin and this binding was inhibited by sLe(X). These results suggest that octapeptide binds to anti-sLe(X) MAb 2H5 or E-selectin at the sLe(X) binding site and sterically interferes with the recognition of anti-sLe(X) MAb 2H5 or E-selectin with sLe(X). This peptide may be a useful lead compound for an anti-inflammatory agent targeting selectin.

Structural basis for the design of novel Schiff base metal chelate inhibitors of trypsin.

The crystal structures of the complexes of bovine trypsin with m-guanidinosalicylidene-l-alaninato(aqua)copper(II) hydrochloride (inhibitor 1), [N,N'-bis(m-guanidinosalicylidene)ethylenediaminato]copper(II) (inhibitor 2), and [N,N'-bis(m-amidinosalicylidene)ethylenediaminato]copper(II) (inhibitor 4) have been determined. The guanidine-containing trypsin-inhibitors (1 and 2) bind to the trypsin active site in a manner similar to that previously reported for amidine-containing inhibitors, for example, m-amidinosalicylidene-l-alaninato(aqua)copper(II) hydrochloride (inhibitor 3). However, the binding mode of the guanidino groups of inhibitors 1 and 2 to Asp189 in the S1 pocket of trypsin was found to be markedly different from that of the amidino group of inhibitor 3. The present X-ray analyses revealed that the interactions of the metal ion of the inhibitors with the active site residues of trypsin play a crucial role in the binding affinity to the trypsin molecule. These structural information and inhibitory activity data for amidine- and guanidine-containing Schiff base metal chelate inhibitors provide new avenues for designing novel inhibitors against physiologically important trypsin-like serine proteases.

Role of estrogen receptors and aromatase on brain protein synthesis rates in ovariectomized female rats fed genistein.

We have reported that the dietary addition of genistein, a phytoestrogen found abundantly in soy products, stimulates brain protein synthesis rates of ovariectomized female rats. In the present study, we determine whether stimulation of brain protein synthesis rates in ovariectomized female rats by the dietary addition of genistein was conducted via estrogen receptors and aromatase-mediating actions. After ovariectomy, Wistar female rats were treated with genistein, the estrogen receptor antagonist ICI 182,780, and/or fadrozole a systemic aromatase inhibitor. In the cerebral cortex, the cerebellum and the hypothalamus, the fractional (Ks) rates of protein synthesis were increased by the dietary addition of genistein. These effects of genistein were inhibited by the administration of ICI 182,780 and fadrozole. However, the degrees to which ICI 182,780 and fadrozole inhibited the effects of genistein differed depending on the brain region. This result suggests that dietary genistein elevates the rate of protein synthesis in the brain of ovariectomized female rats. In addition, the estrogen receptors of the brain and the aromatase of the peripheral tissue and brain are, at least partly, related to the rate of brain protein synthesis caused by genistein.

How can we control intraoperative bacterial contamination and surgical-site infection during an anterior resection or Hartmann's/Miles' operation?

PURPOSE: Intraoperative bacterial contamination (IBC) is a major cause of surgical-site infection (SSI). Therefore, we investigated whether the ingenuity of surgical procedures could reduce the incidence of IBC/SSI. METHODS: Sixty patients who were surgically treated for recto-sigmoid cancer were investigated. Among these patients, the colon was transected during the early perioperative period (ET) in 29 patients and during the late period (LT) in 31 patients. Three samples for IBC were obtained from the irrigation fluid before abdominal closure (LAVAGE), the remaining cut sutures after peritoneal closure (SUTURE), and a subcutaneous swab of the wound (SUBCUT). RESULTS: The overall SSI and IBC rates were 25% and 55.2%, respectively. Patients who developed SSI had an extremely high IBC rate (85%), and IBC patients also had a high SSI rate (68%). IBC was highest in the LAVAGE (26%) followed by the SUBCUT (26%), and the SUTURE (12%). The incidence of IBC in the LT was significantly lower than that in the ET (19% vs. 55%, p < 0.01), although the incidence of SSI was similar in both IBC groups. CONCLUSION: Shortening the exposure of the colonic mucosa decreased the incidence of IBC/SSI; thus, careful operations to minimize IBC are recommended.

Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.

Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100< pmol/mouse) than when administered i.t. (ED(50): 1.34-4.51 pmol/mouse). These results suggest the involvement of nociceptin-like agonistic effects of the Ac-RYYRIK pharmacophore in the peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.

Synthesis and receptor binding properties of chimeric peptides containing a mu-opioid receptor ligand and nociceptin/orphanin FQ receptor ligand Ac-RYYRIK-amide.

Four chimera peptides composed of ORL1 receptor ligand Ac-RYYRIK-NH2 and a mu-opioid receptor agonist dermorphin YAFGYPS-NH2 or YRFB-NH2, with a spacer linking the two pharmacophores, were synthesized and tested for their receptor binding properties. Chimera peptides with long spacers (a Lys and five or eight Gly residues) showed synergistically improved affinity for both the mu-opioid receptor and ORL1 receptor, while the chimera peptides with short spacers (Lys residue only) showed decreased or similar affinity compared to the monomeric receptor ligands. Chimera peptides containing long spacers may prove to be useful tools for studying ORL1 receptor/mu-opioid receptor heterodimers.

ORL1 and opioid receptor preferences of nociceptin and dynorphin A analogues with Dmp substituted for N-terminal aromatic residues.

Nociceptin (NOC) and dynorphin A (DYN) analogues containing 2',6'-dimethylphenylalanine (Dmp) in place of Phe or Tyr in position 1 and/or 4 were synthesized and their metabolic stability and receptor-binding properties were investigated. [Dmp1]NOC(1-13)-NH2 (1) possessed high ORL1 receptor affinity comparable to that of the parent peptide with substantially improved affinities for kappa-, mu-, and delta-opioid receptors. However, Dmp4 substitution of NOC peptide (2) reduced ORL1 receptor affinity. [Dmp1]DYN(1-13)-NH2 (4) and its Dmp4 analogue (5) possessed a 3-fold greater kappa-opioid receptor affinity and improved kappa-receptor selectivity compared to the parent peptide. Analogue 4 however exhibited an unexpectedly low in vitro bioactivity (GPI assay), suggesting, the phenolic hydroxyl group at the N-terminal residue in DYN peptide is extremely important for activation of the kappa-opioid receptor. Analogue 5 possessed an improved kappa-opioid receptor selectivity with an IC50 ratio of 1(kappa)/509(mu)/211598(delta); thus, this peptide may serve as a highly selective kappa-receptor agonist for pharmacological study. Dmp1 substitution in both the NOC and DYN peptides improved metabolic stability toward these peptides, while Dmp4 substitution provided no additional metabolic stability.

[A case of colorectal cancer effectively treated with UFT/LV].

5-FU/LV therapy has been standard chemotherapy for advanced and recurrent colorectal cancer. Several studies reported that a new alternative chemotherapy, UFT/LV, had anti-cancer effects the same as with conventional 5-FU/LV therapy. We report a patient who had advanced and recurrent colorectal cancer treated with UFT/ LV. This 70-year-old male was admitted to our hospital because of a right lower abdominal mass, which was diagnosed as a peritoneal recurrence of transverse colon cancer by abdominal CT. UFT/LV therapy was started on an outpatient basis. After one course of chemotherapy, the intra-abdominal mass disappeared, and this therapy was continued for three courses. He did not suffer from any adverse effect during chemotherapy. Although this therapy was resumed because of the recurrence at the same site after nine months, it was refractory to chemotherapy. Thereafter, surgical resection was performed, and it was diagnosed as lymph node metastasis of previous surgery.