Concentrations of metals and potential metal-binding compounds and speciation of Cd, Zn and Cu in phloem and xylem saps from castor bean plants (Ricinus communis) treated with four levels of cadmium.

We examined the concentrations of metals (Cd, Zn, Cu, Fe and Mn) and potential metal-binding compounds [nicotianamine (NA), thiol compounds and citrate] in xylem and phloem saps from 4-week-old castor bean plants (Ricinus communis) treated with 0 (control), 0.1, 1.0, and 10 µM Cd for 3 weeks. Treatment with 0.1 and 1 µM Cd produced no visible damage, while 10 µM Cd retarded growth. Cadmium concentrations in both saps were higher than those in the culture solution at 0.1 µM, similar at 1.0 µM and lower at 10 µM. Cd at 10 µM reduced Cu and Fe concentrations in both saps. NA concentrations measured by capillary electrophoresis-mass spectrometry (MS) in xylem sap (20 µM) were higher than the Cu concentrations, and those in phloem sap (150 µM) were higher than those of Zn, Fe and Cu combined. Reduced glutathione concentrations differed in xylem and phloem saps (1-2 and 30-150 µM, respectively), but oxidized glutathione concentrations were similar. Phloem sap phytochelatin 2 concentration increased from 0.8 µM in controls to 8 µM in 10 µM Cd. Free citrate was 2-4 µM in xylem sap and 70-100 µM in phloem sap. Total bound forms of Cd in phloem and xylem saps from 1 µM Cd-treated plants were 54 and 8%, respectively. Treatment of phloem sap with proteinaseK reduced high-molecular compounds while increasing fractions of low-molecular Cd-thiol complexes. Zinc-NA, Fe-NA and Cu-NA were identified in the phloem sap fraction of control plants by electrospray ionization time-of-flight MS, and the xylem sap contained Cu-NA.

Extending role by Japanese pharmacists after training for performing vital signs monitoring.

BACKGROUND: In Japan, the circumstances in which pharmacists work are changing. Pharmacists are expected to assess conditions of patients subject to medication to ensure proper use of pharmaceutical products. To ensure fulfilment of these roles, there have already been pharmacists' efforts in performing vital signs monitoring. OBJECTIVE: To clarify the necessity and related issues, by investigating the state of vital sign monitoring in clinical field by pharmacists who have been trained in vital sign monitoring. METHOD: A web survey was conducted from 4th October to 3rd December 2012, subjecting 1,026 pharmacists who completed the vital signs training hosted by The Japanese Association of Home Care Pharmacies (JAHCP). Survey items were 1) basic information of a respondent, 2) situation of homecare conducted by pharmacists, 3) seminar attendance status, and 4) vital signs monitoring status after the seminar. RESULTS: The number of valid respondents was 430 and the response rate was 41.9%. As a result of the present research, it was revealed that 168 pharmacists (41.4%), had the opportunity to perform vital signs monitoring. By conducting vital sign monitoring, effects such as 1) improved motivation of pharmacists and better communication with patients, 2) proper use of medication, and 3) cost reduction were confirmed. CONCLUSION: Judging from the results of the survey, pharmacists can improve medication therapy for patients by attaining vital sign skills and conduct vital sign monitoring. Pharmacists who perform vital sign monitoring should share cases where they experienced positive patient outcomes.

Extending role by Japanese pharmacists after training for performing vital signs monitoring / Ampliando el papel de los farmacéuticos japoneses después de una formación para realizar monitorización de signos vitales

Background: In Japan, the circumstances in which pharmacists work are changing. Pharmacists are expected to assess conditions of patients subject to medication to ensure proper use of pharmaceutical products. To ensure fulfilment of these roles, there have already been pharmacists’ efforts in performing vital signs monitoring. Objective: To clarify the necessity and related issues, by investigating the state of vital sign monitoring in clinical field by pharmacists who have been trained in vital sign monitoring. Method: A web survey was conducted from 4th October to 3rd December 2012, subjecting 1,026 pharmacists who completed the vital signs training hosted by The Japanese Association of Home Care Pharmacies (JAHCP). Survey items were 1) basic information of a respondent, 2) situation of homecare conducted by pharmacists, 3) seminar attendance status, and 4) vital signs monitoring status after the seminar. Results: The number of valid respondents was 430 and the response rate was 41.9%. As a result of the present research, it was revealed that 168 pharmacists (41.4%), had the opportunity to perform vital signs monitoring. By conducting vital sign monitoring, effects such as 1)improved motivation of pharmacists and better communication with patients, 2) proper use of medication, and 3) cost reduction were confirmed. Conclusion: Judging from the results of the survey, pharmacists can improve medication therapy for patients by attaining vital sign skills and conduct vital sign monitoring. Pharmacists who perform vital sign monitoring should share cases where they experienced positive patient outcomes (AU)

Antecedentes: En Japón, las circunstancias en las que trabajan los farmacéuticos están cambiando. Se espera que los farmacéuticos evalúen los problemas de salud que están siendo tratados con medicación para asegurar el uso adecuado de los medicamentos. Para asegurar el cumplimiento de este papel, los farmacéuticos han iniciado esfuerzos para realizar monitorización de signos vitales. Objetivo: Clarificar la necesidad y problemas asociados, investigando el estado de la monitorización de signos vitales en la práctica clínica por farmacéuticos que fueron entrenados en monitorización de signos vitales. Método: Se realizó un cuestionario online de 4 de octubre a 3 de diciembre de 2012, alcanzando a 1.026 farmacéuticos que habían completado el entrenamiento en signos vitales realizado por la Asociación Japonesa de Farmacias Comunitarias (JAHCP). Los ítems del cuestionario fueron. 1) información básica del encuestado, 2) situación de la atención domiciliaria realizada por farmacéuticos, 3) situación de la asistencia al seminario, y 4) estado de la monitorización de signos vitales después del seminario. Resultados: El número de respondentes válidos fue de 430 y la tasa de respuesta fue del 41,9%. Como resultado de esta investigación, se descubrió que 168 farmacéuticos (41,4%) tuvo la oportunidad de realizar monitorización de signos vitales. Al realizar monitorización de signos vitales se confirmaron efectos tales como 1) mejora de la motivación delos farmacéuticos y mejor comunicación con los pacientes, 2) uso adecuado de la medicación, y 3) reducción de costes. Conclusión: Juzgando los resultados de la encuesta, los farmacéuticos pueden mejorar el tratamiento medicamentosos de los pacientes mediante la adquisición de habilidades en signos vitales y realizando monitorización de signos vitales. Los farmacéuticos que realizan monitorización de signos vitales deberían compartir los casos que hayan visto de resultados positivos de pacientes (AU)

[The novel image of pharmacist of a super-aged society in Japan].

The percentage of the population over age 65 in Japan was greater than 23% in 2010. Therefore, Japan is the world's first "super-aged society", and our country needs a new regional health care system. Our medical systems face many challenges, such as this increase in elderly population with chronic diseases, maintenance of universal health insurance and free access to hospitals, and expensive health care costs. It is not easy to change the current health care system without a sufficient number of doctors. On the other hand, Japan's curriculum in pharmaceutical education has been expanded to six years to establish a new profession of pharmacist. Rapid progress in the market of pharmacies in accepting prescriptions since 1974 has caused pharmacists to primarily act as "technicians". But this is not the best way to solve the serious problems of Japanese medical systems. I want to present the image of a next-generation pharmacist (Pharmacist 3.0), to be involved in the idea of collaborative drug therapy management (CDTM) in this article. The total optimization of our medical supply system with all medical and pharmaceutical specialists is necessary in Japan.

["Pharmacy 3.0" and the meaning of vital signs for pharmacists].

In Japan, the proportion of elderly people had reached up to 23% in 2009. The number of elderly people in long-term nursing homes or nursing facilities will increase in the next decade. By 2025, the majority of the elderly people would have developed cancer, stroke, cardio-vascular diseases, and dementia. Almost all of them would be treated with prescribed drugs. They would also have dysphagia and have difficulties in remembering their medications in the long term. Therefore, for the benefit of such a community, the work force, especially in the field of drug distribution, will need to be increased to prevent the incidence of patients who forget to take their medications. Further, the educational curriculum for pharmaceutical students has been changed to a new version, and some Japanese pharmacy shops have been switching over to "Pharmacy 3.0," which is the next generation model. In this pharmacy, the pharmacists will play an additional new role; they will not only dispense drugs but also support home recuperation leveraging some vital signs and physical assessments. In my opinion, this novel scheme of medical service developed with pharmacists playing this new role may be a boon to the patient/elderly community in Japan who are facing the collapse of healthcare systems. In conclusion, Collaborative Drug Therapy Management (CDTM) in the practice of the pharmacists is essential for increasing the efficiency of the Japanese healthcare systems.

[Thoughts on a program for pharmaceutical practice].

The educational curriculum for pharmaceutical students in Japan will be dramatically changed in April, 2006. There has been active discussion about how to manage the additional two years in the new program to educate students most effectively. In particular, the program of clinical practice in pharmacies, which will be undertaken for 10 weeks, has been received enthusiastically, because it was not considered sufficient in the previous educational program and it will be one of the most important issues in the new curriculum. I am neither a pharmacist nor a professional in pharmaceutical education, but I believe firmly that an effective program of clinical practice in community pharmacies will be indispensable in making the new curriculum successful. I also believe that community pharmacists educated in the new course will change medical systems in this country from the viewpoint of a general thoracic surgeon and chief executive officer of Pharmedico, Co., Ltd. which manages eight pharmacies in Osaka, Japan. In this article, I give my opinions on the advisable vector of clinical practice for pharmaceutical students and the direction of clinical training in the new educational program.

A novel strategy for preventing PERV transmission to human cells by remodeling the viral envelope glycoprotein.

BACKGROUND: Porcine endogenous retrovirus (PERV) released from pig cells is a main problem associated with clinical xenotransplantation. In a previous study, we demonstrated that the high mannose type of N-glycan of the envelope glycoprotein is closely related to PERV infectivity with respect to human cells. In this study, we addressed the effects of reducing the high mannose type of N-glycan on PERV infectivity. METHODS: Pig endothelial cells (PEC) were transduced with the LacZ gene by a pseudotype infection to produce PEC(Z). The PEC(Z)s were then further infected with PERV subtype B (PERV-B) to produce PEC(Z)/PB. The PEC(Z)/PBs were next transfected with the alpha 1,2 mannosidase Ib (Man Ib), N-acetylglucosaminyltransferase I (GnT-I) or alpha-mannosidase II (Man II) gene in order to reduce the levels of high mannose type of N-glycan. HEK293 cells were inoculated with the PERV in each of the culture supernatants. The inoculated cells were histochemically stained and the LacZ-positive cells were counted. RESULTS: In experiment I, PERV transmission from the PEC(Z)/PB with GnT-I or Man II to HEK 293 cells was significantly reduced in comparison with control PEC(Z)/PB, while the PEC(Z)/PB with Man Ib was not. However, in experiment II, PERV transmission from the PEC(Z)/PB with ManIb to HEK 293 cells was also significantly reduced in comparison with control PEC(Z)/PB. CONCLUSION: The transfection of these genes to pig cells is effective in reducing the susceptibility of human cells to PERV infection. The results suggest that this represents a potentially useful strategy for further decreasing the likelihood of PERV infections.

Prevention of PERV infections in pig to human xenotransplantation by the RNA interference silences gene.

The possibility of preventing the transmission of porcine endogenous retrovirus (PERV) to human cells using short interfering RNAs (siRNA) was investigated. The siRNA for the p30 of PERV gag region was cloned into pSUPER, the polymerase-III H1-RNA gene promoter. A green fluorescence protein (GFP) was also cloned into pSUPER to establish pSXGH. Pig endothelial cells (PEC) were transduced with the LacZ gene by pseudotype infection, and infected with PERV subtype B, resulting in the formation of PEC(LacZ)/PB. The PEC(LacZ)/PB was next transfected with pSXGH-siRNA. The expression of siRNA was provisionally checked by determining the level of expression of GFP. Culture supernatants of infected cells were then inoculated into HEK293 cells. The siRNA clearly destroyed the PERV infectivity of PEC(LacZ)/PB in both transient cell lines and stable clones. Moreover, the decreased levels of mRNA and gag protein were evidenced in the stable clones by real-time PCR and Western blotting, respectively. The final goal of our study was to establish a transgenic pig expressing the siRNA for PERV. The results suggest that siRNA represents a novel approach for controlling PERV infections in clinical xenotransplantation.

Pleural perfusion thermo-chemotherapy under VATS: a new less invasive modality for advanced lung cancer with pleural spread.

BACKGROUND: We conducted a trial of a new less invasive, locoregional modality for lung cancer with pleural spread. This study was planned to investigate the feasibility, safety, and pharmacokinetics of pleural perfusion thermochemotherapy (PPTC) under video-assisted thoracoscopic surgery (VATS) and its modified method with a short perfusion time for preventing heat damage to the lung during the procedure. METHODS: Seventeen patients, 59 to 79 years old, underwent surgical resection of the primary lesions and PPTC under VATS without thoracotomy. All had pleural spread with malignant effusion due to lung cancer proven before the treatment. PPTC consists of irrigating the pleural space with 42 degrees C saline solution containing cisplatin (200 mg/m(2)) using a devised circuit. The time for perfusion was two hours in 10 patients (group L), and one hour in 7 patients (group S). RESULTS: All patients successfully completed this treatment with acceptable toxicities. The pharmacokinetic analysis showed that high platinum levels for the regional pleural exposure, which was 20- to 40-fold greater than those for the plasma in both groups. These values were equivalent between the groups, although the levels for the plasma were higher in group L than in group S. Postoperative lung damage was seen in 4 patients with no serious conditions in group L, and none in group S. The median survival for the L and S groups was 17 and 19 months, respectively. CONCLUSIONS: This less invasive modality seems to offer a safe, feasible, and pharmacokinetically advantageous procedure to have excellent local control for lung cancer with pleural spread.

The significance of N-linked glycosylation in pig endogenous retrovirus infectivity.

The significance of the envelope glycoprotein in the transmission of pig endogenous retrovirus (PERV) to human cells was investigated. Pig endothelial cells (PEC) were transduced with the LacZ gene by a pseudotype infection and then infected with PERV subtype B. Culture supernatants of the infected PEC previously incubated with several types of drugs were inoculated into HEK293 cells. The inoculated cells were then stained and the number of LacZ-positive foci was counted. PERV from tunicamycin treated PEC was not transmitted to human cells, indicating the importance of N-linked sugars in this process. Moreover, while inhibition of the terminal alpha-glucose residues from the precursor N-glycan by castanospermine and 1-deoxynojirimycin attenuated PERV infectivity, the mannosidase inhibitors, 1-deoxymannojirimycin and swainsonine, upregulated the infectivity. In addition, treatment with alpha-mannosidase and incubation with concanavalin A completely abrogated the transmission of PERV to HEK293. These data imply that the high-mannose type of N-glycan plays a key role in PERV infectivity.

Less invasive needle thoracoscopic laser ablation of small bullae for primary spontaneous pneumothorax.

OBJECTIVE: The purpose of this study was to establish a new surgical technique of thoracoscopic laser ablation for the patients of primary spontaneous pneumothorax (PSP) with small bullae, by using endoscopic equipment with a 2-mm diameter. METHOD: According to the size of a bulla identified by high-resolution computed tomography (HRCT), we have a protocol to determine an indication; the conventional video-assisted thoracic surgery (VATS) procedure by both stapler bullectomy and laser ablation to visceral pleura surrounding the bulla (bullae size: greater than 2 cm), or a new VATS procedure using needle shaped thoracoscopy and endoscopic equipment with a 2-mm diameter (needle VATS) by laser bulla ablation alone (bullae size: less than 2 cm). RESULTS: The conventional VATS was performed in 54 patients and needle VATS in 60 patients. In the needle VATS group, operation time was shorter than that of the VATS group (39+/-17 min vs. 56+/-22 min). Use of non-steroidal anti-inflammatory drugs for postoperative wound pain could be reduced in the needle VATS group (3% vs. 56%). There were no complications in the needle VATS group, but three complications (5.6%) in the VATS group, including prolonged air leakage (>4 days) in two and refractory intercostal pain in one. The rate of recurrence after the operation was similar in both groups (3.7% vs. 3.3%). The needle VATS allowed wound healing without a scar and reduced the patient's cosmetic problems. CONCLUSION: The needle VATS procedure for patients with a bulla size less than 2-cm diameter was as useful as the conventional VATS procedure.

Combined right atrial resection for lung cancer that developed intractable atrial flutter.

We have encountered a patient with primary lung cancer with invasion into the right atrial wall with N2 disease. Complete resection of the tumor combined with the right atrial wall was achieved under cardiopulmonary bypass after induction chemoradiotherapy. Pathological results confirmed ypT0N0M0. Postoperatively, atrial flutter resistant to rate control with calcium-antagonists and beta-blockers was treated with catheter ablation of the atrioventricular node.

Clinicopathological investigation of 20 cases of primary tracheal cancer.

OBJECTIVE: Primary tracheal cancer is considered to be relatively rare. Its epidemiology, therapeutic strategy and prognosis are not well understood. METHODS: We retrospectively investigated the clinicopathological aspects of 20 patients with primary tracheal cancer. RESULTS: Patients included 11 men and nine women with a mean age of 57.3 years. There were 12 squamous cell carcinomas and eight adenoid cystic carcinomas. Four patients received only palliative therapy. Sixteen patients underwent surgical treatment such as segmental tracheal, laryngotracheal, or carinal resection. One patient with squamous cell carcinoma died of postoperative mediastinitis. Although resected specimens from five patients had tumor positive margins, only one of those patients died after local recurrence and only three patients had postoperative treatment. The 5-year survival rate for patients who underwent surgery was 72.3%. CONCLUSIONS: Surgical treatment is the first choice therapeutic modality for primary tracheal cancer in consideration of its prognosis. While performing the operation, safety of the anastomosis should take precedence over completeness of resection.

Matured mediastinal teratoma extending into the cervical neck of an adult.

Teratomas have been reported to occur in various sites and organs. Cervical neck teratomas are relatively rare in adulthood, and mediastinal teratomas that extend into the cervical neck are also rare. Therefore, we report a case of a matured teratoma found in the cervical tumor of an adult. A 27-year-old woman was admitted with a cervical soft tumor. Preoperative examination revealed a cystic mass in the upper mediastinum that extended to the thyroid. We diagnosed this as a thymic or foregut cyst and removed the tumor via a collar incision. Histological examination revealed a benign mature teratoma.

Sensitivity to human serum of gammaretroviruses produced from pig endothelial cells transduced with glycosyltransferase genes.

Reduction of pig cell-surface alpha-galactosyl (Gal) epitope, Galalpha1, 3Galbeta1, 4GlcNAc-R, by the introduction of glycosyltransferase genes is effective in suppressing hyperacute rejection (HAR) in pig-to-human xenotransplantation. The transmission of porcine endogenous retroviruses (PERVs) has been recognized as a potential risk factor associated with xenotransplantation. In this study, effects of the introduction of glycosyltransferase genes to pig cells on the sensitivity of gammaretroviruses to human serum were investigated. Pig endothelial cells (PEC), PEC transduced with alpha1,2 fucosyltransferase (FT), alpha2,3 sialyltransferase (ST), or N-acetylglucosaminyltransferase III (GnT-III), and human embryonic kidney (HEK) 293 cells were transduced with the LacZ gene with the packaging signal of murine leukemia virus (MuLV) under the control of the long terminal repeat of MuLV by a pseudotype infection. Then, the cells were further infected with PERV subtype B (PERV-B) or feline leukemia virus subgroup B (FeLV-B). Culture supernatants of the infected cells were mixed with human serum (HS) and then inoculated to HEK293 cells. The inoculated cells were histochemically stained and lacZ-positive blue foci were counted. Glycosyltransferase activity, xenoantigenicity, and alpha-Gal epitope density in the cells were measured at the time of the infection experiments. PERV-B or FeLV-B particles from the parental PEC were efficiently neutralized by HS, while those from PEC transduced with alpha1,2FT, alpha2,3ST or GnT-III were less sensitive to HS. The transduced PEC exhibited high levels of activity of the introduced glycotransferases, and expressed fewer xenoantigens and cell-surface alpha-Gal epitopes. Our results suggest that gammaretroviruses including PERVs produced by transgenic pigs, that are generally modified to reduce the cell-surface alpha-Gal epitope to overcome the HAR in xenotransplantation, are less sensitive to HS.

Bilateral cervicomediastinal neurofibroma originating from the vagal nerve in a patient with von Recklinghausen's disease: report of a case.

A 19-year-old woman with von Recklinghausen's disease was admitted with symptoms of hoarseness. A computed tomography scan showed a bilateral cervicomediastinal tumor. An extirpation of the left cervicomediastinal tumor was performed for the purpose of diagnosis and treatment. On thoracotomy, the tumor, which measured 9 x 8 x 4 cm in size, arose from the intrathoracic vagal nerve and the left tumor was resected with a segment of the vagal nerve and recurrent nerve. The pathological diagnosis of the tumor was a neurofibroma. The tumor on the right side was left untreated due to concerns about possibly causing palsy of the bilateral recurrent nerve and also because of the asymptomatic state of the right tumor. Mediastinal neurofibroma in a patient with von Recklinghausen's disease often arises from the intrathoracic vagal nerve. To our knowledge, this is the first report of bilateral cervicomediastinal neurofibroma originating from the vagal nerves.