Determination of deuterium incorporation of new drug donafenib tosilate by two methods of LC-MS with natural isotope abundance correction and 1H NMR relative quantitative method / 药学学报

An LC-MS method with natural isotope abundance correction and a 1H NMR relative quantitative method were established to determine the deuterium incorporation of donafenib tosilate, a new deuterated drug molecule. First, the peak areas of isotopic impurities (non-deuterated and incompletely deuterated impurities) and deuterated drug were recorded through the single ion monitoring (SIM) mode of the established LC-MS method and then corrected in terms of the natural isotope abundance offered by ChemDraw soft, removing the nature isotope interference from 13C, 37Cl, etc. The corrected areas were subsequently used to calculate mol% of isotopologues (D0, D1, D2, D3) and Atom% D, namely, deuterium incorporation. In addition, a 1H qNMR experiment was conducted with the aromatic proton at δ 8.63 and the residual proton of isotopic impurities at δ 2.79 as quantitative peaks. The mixture of DMSO-d6 and D2O (10∶1) was employed as the solvent to change the spin-coupling between the residual proton and active hydrogen so that the residual proton could be measured as the single peak, and the sensitivity was greatly improved. The acquisition parameters were also optimized, and Atom% 1H and the deuterium incorporation were then calculated. The two methods were applied to samples of three commercial batches, and the testing results were almost consistent. Both methods proved accurate, sensitive, fast and independent of standard substances and accurate weighing, which could be applied to the determination of the deuterium incorporation of donafenib tosilate and provide a reference for other deuterated drugs.

Effect of age on reversible lens opacity and Na⁺-K⁺-ATPase expression induced by chloral hydrate in mice / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the effect of age on the expression of Na⁺-K⁺-ATPase and acute reversible lens opacification induced by chloral hydrate in mice. <p>METHODS: Acute reversible lens opacification was induced by intraperitoneal injection of 4% chloral hydrate(400mg/kg)in 3-month-old(young group)and 24-month-old(old group)C57BL/6 mice. The lens opacification was graded at 10, 20, 30, 45, 60, 90, 120 and 150min after chloral hydrate injection. The histopathological changes of lens were observed by hematoxylin eosin staining, and the expression of Na⁺-K⁺-ATPase in lens was detected by immunohistochemistry. <p>RESULTS: The development of lens opacity is similar in young and old mice after chloral hydrate injection. The lens opacification in the young group appeared earlier, thicker and lasted longer than the old group. HE staining showed that many vesicles appeared in the cortex below lens epithelial cells(LECs), and the structure of superficial lens fiber cells were disordered after chloral hydrate injection. Immunohistochemical staining showed that the expression of Na⁺-K⁺-ATPase was positive in LECs and fibers. The expression of Na⁺-K⁺-ATPase in LECs were weak before chloral hydrate injection and up-regulated 45min after chloral hydrate injection in young and old groups. The up-regulation of Na⁺-K⁺-ATPase was stronger in the old group than in the young group. <p>CONCLUSION: Age may play a role in the acute reversible lens opacification induced by chloral hydrate in mice. The expression of Na⁺-K⁺-ATPase is involved in lens opacity induced by chloral hydrate.

Staged Approach Using Proximal Open-Stenting Technique and Distal Open Repair for the Treatment of Extensive Thoracic Aortic Aneurysms / 日本心臓血管外科学会雑誌

<p>A 50-year-old man with an extensive thoracic aortic aneurysm underwent staged surgery which consisted of preceding total aortic arch replacement with the frozen elephant trunk technique using J Graft Open Stent Graft^®, followed by open thoracoabdominal aortic aneurysm repair. During the second operation, the descending aorta was cross clamped along with the preexisting stent graft, and Dacron graft was anastomosed directly to the stent graft using a running 4-0 monofilament suture. The anastomosis site was then covered with a short piece of Dacron graft identical with the stent graft in size to secure hemostasis. We herein discuss our approach in this complex case, focusing on prevention of inadvertent events such as deformation of the preexisting stent graft and unexpected bleeding.</p>

<b>3．Revision of Procedures for Appropriate Management of Revlimid</b>^® <b>and Pomalyst</b>^® （<b>RevMate</b>^®）<b>and Iss / 薬剤疫学

<p>RevMate^®is one of risk minimization activities in Japanese RMPs of Revlimd^®and Pomalyst^®, of which indications are hematological malignancy including multiple myeloma. This is a proper management procedure approved by Japanese health authorities in order to prevent exposure to pregnant women because these agents are derivatives of thalidomide. RevMate^® was revised in 2015 after the discussion in MHLW's Taskforce and its operation started from April 2016. Due to this revision of version 5.0, the manufacture no longer receives the patient name, and this and other information must be managed by the hospital. In addition, with regard to the same objective in the format used in the management procedure（TERMS^®）of thalidomide drug products, unification was attempted concerning the name of the format and</p><p>the notation of confirmation items. Physician becomes to make judgment to omit explanation of some RevMate^® requirements based on the patient's level of their understandings to RevMate^®.Periodical survey sheet regarding compliance with RevMate^® requirement filled by a patient is to be submitted directly to a physician on his/her visit instead of sending it to the manufacturer by mail under previous procedures. A representative person of the manufacture is required to visit the hospital periodically and confirm filing condition of the survey sheets and compliance check lists of RevMate^® for every prescription as well appropriately at the hospital. Furthermore, RevMate^® was revised to add clear role description of relevant pharmacists and nurses for in-patients and its strict drug-handling procedures at bedside as version 5.1, as we received four reports from hospitals of medication error of our drug to the another patient in the hospital within 2016. After getting approval of additional indications for Revlimid^® from March 2017, RevMate^® of version 5.2 started. In the view of implement RevMate^® as strict “risk minimization activities” to prevent pregnant women from exposure, we will continue to solve each problem recognized from the actual operation, constantly keep basics in mind by providing necessary training to our employees about thalidomide drug problem etc. In addition, we appreciate the understanding and support from the patient, patient family, Healthcare Professional, etc. involved in this procedure without incompleteness as well as non-compliance with procedures caused by habituation. Including all these, we consider it is important to endeavor as a manufacture continuously in the future.</p>

Investigation of Nutritional Risk and Nutritional Support among Inpatients in Departments of Spinal Surgery and Minimally Invasive Spinal Surgery of Our Hospital / 中国药房

OBJECTIVE:To provide reference for investigating the nutrition situation of the inpatients in departments of spinal surgery and minimally invasive spinal surgery and promoting the clinical rational use of nutritional support drugs. METHODS:Des-ignated continuous sampling was used to select the inpatients that fit the conditions in the departments of spinal surgery and mini-mally invasive spinal surgery in our hospital from Jan. to Dec. 2013,and the nutritional risk screening 2002 was used to investigate the patients’nutritional risk at admission and upon discharge,the nutritional support during hospitalization were recorded. RE-SULTS:In the 432 enrolled patients,the overall incidence of nutritional risk was 11.57% at admission,12.40% in spinal surgery and 10.44% in minimally invasive spinal surgery;and the overall incidence of nutritional risk was 19.44% upon discharge, 23.60% in spinal surgery,with statistical significance when compared with admission(P0.05). The nutritional support rate of 50 pa-tients with nutritional risk at admission was 88.00%,14.14% of 382 non-risk patients still received a redundant nutritional support. The 44 patients with nutritional risk who received nutritional support had the average calories intake of(9.84±8.10)kJ/(kg·d),in-cluding 10.16% lipids and 9.55% protein;all patients who received nutritional support found no patients with enteral nutrition sup-port. CONCLUSIONS:Inpatients in departments of spinal surgery and minimally invasive spinal surgery suffer a lower incidence of nutritional risk at admission,and a higher incidence of nutritional risk in the former one upon discharge. While some patients who received nutritional support show no indication,and administrations of nutritional support are still debatable,the use of drug is irrational.

The Case of a Patient with Femoral Artery Stenosis Caused by Angio-Seal^® Use Treated with Endoarterectomy / 日本心臓血管外科学会雑誌

In cases of hemostasis of the femoral artery where the sheath is removed after percutaneous catheterization, there is greater improvement in patient condition and shorter duration of hospital stay when arterial puncture closing devices are used rather than standard manual compression because the use of these devices results in shorter hemostasis and rest times. However, some complications due to these devices have also been reported. Here, we report a case of femoral artery stenosis due to Angio-Seal^® use in a 67-year-old woman. Embolization of the basilar artery aneurysm by endovascular treatment was performed at another institution ; the percutaneous puncture site was the right femoral artery. When this treatment was provided, hemostasis of the artery was performed with the Angio-Seal^®. About one month after the embolization, right intermittent claudication occurred after a 300-m walk. Echography and computed tomography (CT) angiogram showed 75% stenosis of the right common femoral artery, and therefore endoarterectomy of the artery was performed. The postoperative course was favorable and the ankle brachial index score improved from 0.82 to 1.15. In addition, CT angiogram showed resolution of the stenosis of the right common femoral artery and right intermittent claudication ameliorated. Based on the intraoperative views, it was suggested that the arteriosclerotic lesion had existed at the common femoral artery before the endovascular treatment and it might be the cause of the complication mentioned above. In order to prevent complications due to Angio-Seal^® use, it is important to examine the indications of the use of this device by evaluating the puncture site of the artery with echography and other diagnostic techniques before the insertion of a sheath.

Application of the BacT/ALERTR 3D system for sterility testing of injectable products

Sterility testing as described in the pharmacopoeia compendia requires a 14-day incubation period to obtain an analytical result. Alternative methods that could be applied to evaluating product sterility are especially interesting due to the possibility of reducing this incubation period and thus the associated costs. The aims of this study were to evaluate the performance of the BacT/ALERT^R 3D system in detecting microorganisms in large-volume parenteral solutions that were intentionally contaminated and to compare this system to pharmacopoeia sterility testing using the membrane filtration method. The results indicated that there were no significant differences between the methods regarding the ability to detect microbial contamination; however, detection with the BacT/ALERT^R 3D system was faster compared to the pharmacopoeia method. Therefore, the BacT/ALERT^R 3D system is a viable alternative for assessing the sterility of injectable products.

Sensitivity of imidazolinone-resistant red rice (Oryza sativa L.) to glyphosate and glufosinate / Sensibilidade de arroz-vermelho (Oryza sativa L.) resistente às imidazolinonas, aos herbicidas glyphosate e glufosinate

Dose-response experiments were carried out to evaluate the sensitivity of imidazolinone-resistant red rice to nonselective herbicides currently used in rice-soybean rotation in Rio Grande do Sul. Two red rice biotypes previously identified as resistant and susceptible to the imidazolinone herbicides were treated with imazapic plus imazapic, glyphosate and glufosinate under nine herbicide rates. A non-linear log-logistic analysis was used to estimate the herbicide rate that provided 50% red rice control and dry weight reduction (GR₅₀). Imidazolinone-resistant red rice exhibited greater GR₅₀ values than imidazolinone-susceptible biotype for imazapyr plus imazapic. In contrast, both imidazolinone-resistant and susceptible red rice showed similar GR₅₀values for glyphosate and glufosinate. These results indicate that glyphosate and glufosinate effectively control imidazolinone-resistant red rice at similar herbicide rates used to control imidazolinone-susceptible; however, integrated weed management practices must be adopted in rice-soybean rotation to delay resistance evolution of red rice populations to glyphosate and glufosinate

Curvas de dose-resposta foram conduzidas para avaliar a sensibilidade de arroz-vermelho resistente às imidazolinonas para herbicidas não-seletivos, comumente utilizados em áreas de rotação soja-arroz irrigado no Rio Grande do Sul. Dois biótipos de arroz-vermelho, previamente identificados como suscetível e resistente às imidazolinonas, foram aspergidos com imazapyr+imazapic, glyphosate e glufosinate sob nove concentrações herbicidas. Utilizou-se análise de regressão não linear do tipo log-logística para estimar a concentração herbicida que proporcionou 50% de controle e redução na massa de matéria seca da parte aérea (GR₅₀) de arroz-vermelho. O biótipo de arroz-vermelho resistente às imidazolinonas demonstrou maior GR₅₀, quando comparado ao biótipo suscetível para imazapyr+imazapic. Valores similares de GR₅₀ foram observados para ambos os biótipos tratados com glyphosate e glufosinate. Esses resultados indicam que os herbicidas glyphosate e glufosinate controlam efetivamente biótipos de arroz-vermelho resistente às imidazolinonas em doses recomendadas para controlar biótipos suscetíveis às imidazolinonas. No entanto, práticas integradas de manejo devem ser utilizadas para retardar a evolução da resistência de arroz-vermelho aos herbicidas glyphosate e glufosinate na rotação soja-arroz irrigado

T-cell receptor Vβ repertoire of CD8+ T-lymphocyte subpopulations in cutaneous leishmaniasis patients from the state of Rio de Janeiro, Brazil

In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8⁺ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8⁺ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8⁺ T-lymphocytes showed a disturbance in the expression of the Vβ2, Vβ9, Vβ13.2, Vβ18 and Vβ23 families. The analyses of CD8⁺T-lymphocyte subsets showed high frequencies of LDE CD8⁺T-lymphocytes expressing Vβ12 and Vβ22 in PAD, as well as effector-memory CD8⁺ T-cells expressing Vβ22. We also observed low frequencies of effector and central-memory CD8⁺ T-cells expressing Vβ2 in PAD, which correlated with a greater lesion size. Particular Vβ expansions point to CD8⁺ T-cell clones that are selected during CL immune responses, suggesting that CD8⁺ T-lymphocytes expressing Vβ12 or Vβ22 are involved in a LDE response and that Vβ2 contractions in memory CD8⁺T-cells are associated with larger lesions.

Can mouth washes containing chlorhexidine 0.12% be used as synonym of a water solution of chlorhexidine 0.12%? / Pode lavagens da boca contendo 0.12 % de clorexidina ser utilizado como sinónimo de uma solução aquosa de cloro-hexidina 0.12 % ?

Chlorhexidine digluconate (CHX) is a gold standard drug in dentistry and is widely used as a reference in both in vitro and in vivoexperiments. Due to ease of access, mouth washes containing CHX 0.12% are used as a substitute for aqueous CHX 0.12% solution in laboratory experiments. Additionally, it is well known that for product flavor purposes, volatile compounds are added to mouth washes formulations. Volatiles added to CHX 0.12% may improve wash's antibacterial ability. Volatiles add potency to the mouth wash formulation. Compared with an aqueous CHX 0.12% solution, it is proposed that CHX solutions and Periogard^® would have antimicrobial activity. Antimicrobial activity was assessed in the present study via disk diffusion assays against Streptococcus mutans, Streptococcus sanguinisand Escherichia coli. Periogard^® showed a significantly higher antibacterial activity in relation to CHX 0.12% (p<0.05) and a similar activity in relation to CHX 1% (p>0.05). Periogard^(r) volatiles were analyzed by gas-chromatography/mass spectrometry (GCMS) and the presence of antibacterial menthol, menthone, isomenthol, menthyl acetate, trans-anethol and eugenol was verified. Finally, the use of Periogard^® as a synonym of CHX 0.12% must be avoided, because its antibacterial activity is closely related to CHX 1%...

Gluconato de clorexidina (CHX) é um fármaco considerado padrão ouro, em Odontologia, amplamente usado como referência em estudos in vitro e in vivo. Em razão da facilidade de acesso, enxaguatórios bucais que contêm CHX 0,12% são usados em substituição à solução aquosa de clorexidina (CHX 0,12%), em experimentos laboratoriais. É sabido que devido à palatabilidade do produto, os mesmos enxaguatórios bucais contêm compostos voláteis em sua formulação, além da CHX 0.12%. Visto que voláteis adicionados podem acrescentar poder antibacteriano à formulação, a comparação da resposta antibacteriana da solução aquosa de CHX em diferentes concentrações e de Periogard^® é proposta no presente artigo. Para tanto, utilizou-se o ensaio do disco de difusão em ágar com inóculos de Streptococcus mutans, Streptococcus sanguinis e Escherichia coli. Periogard^® mostrou atividade antibacteriana significativa contra as três cepas analisadas, quando comparada à atividade de CHX 0.12% (p<0,05) e atividade similar à CHX diluída a 1% (p>0,05). A presença de compostos voláteis no Periogard^® foi analisada por GC-MS e observou-se que mentol, mentona, isomentol, acetato de mentila, trans-anetol e eugenol estão presentes na formulação. Deste modo, o uso de Periogard^(r) como sinônimo de CHX 0,12% deve ser evitado, uma vez que sua atividade se assemelha àquela da CHX diluída a 1%...

Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent / Produção, controle de qualidade, avaliação de biodistribuição e avaliação da dose preliminar de [177Lu] -tetra complexo fenil porfirina como um possível agente terapêutico

Due to interesting therapeutic properties of ¹⁷⁷Lu and tumor avidity of tetraphenyl porphyrins (TPPs), ¹⁷⁷Lu-tetraphenyl porphyrin was developed as a possible therapeutic compound. ¹⁷⁷Lu of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu₂O₃sample with thermal neutron flux of 4 × 10¹³ n.cm^-2.s^-1. Tetraphenyl porphyrin was synthetized and labeled with ¹⁷⁷Lu. Radiochemical purity of the complex was studied using Instant thin layer chromatography (ITLC) method. Stability of the complex was checked in final formulation and human serum for 48 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied up to 7 d. The absorbed dose of each human organ was calculated by medical internal radiation dose (MIRD) method. A detailed comparative pharmacokinetic study was performed for ¹⁷⁷Lu cation and [¹⁷⁷Lu]-TPP. The complex was prepared with a radiochemical purity: >97±1% and specific activity: 970-1000 MBq/mmol. Biodistribution data and dosimetric results showed that all tissues receive approximately an insignificant absorbed dose due to rapid excretion of the complex through the urinary tract. [¹⁷⁷Lu]-TPP can be an interesting tumor targeting agent due to low liver uptake and very low absorbed dose of approximately 0.036 to the total body of human...

Devido às propriedades interessantes do ¹⁷⁷Lu e da avidez tumoral das tetrafenil porfirinas (TPP), desenvolveu-se a ¹⁷⁷Lu-tetrafenil porfirina como composto terapêutico potencial. ¹⁷⁷Lu de atividade específica de 2,6-3 GBq/mg foi obtido por irradiação de amostra de Lu₂O₃ com fluxo térmico de nêutrons de 4 × 10¹³ n.cm^-2.s^-1. Sintetizou-se a tetrafenil porfirina e marcou-se com ¹⁷⁷Lu. A pureza radioquímica do complexo foi estudada usando método de Cromatografia Instantânea de Camada Delgada ( ITLC). A estabilidade do complexo foi checada na formulação final e no ser humano por 48 h. A biodistribuição do composto marcado em órgãos vitais de ratos do tipo selvagem foi estudada por mais de 7 dias. A dose absorvida para cada órgão humano foi calculada pelo método da Dose Médica de Radiação Interna (MIRD). Estudo farmacocinético comparativo detalhado foi efetuado para o cátion ¹⁷⁷Lu e para o [¹⁷⁷Lu]-TPP. O complexo foi preparado com pureza radioquímica >97±1% e atividade específica de 970-1000 MBq/mmol. Os dados de biodistribuição e os resultados dosimétricos mostraram que todos os tecidos receberam uma dose absorvida aproximadamente insignificante devido à rápida excreção do complexo pelo trato urinário. O [¹⁷⁷Lu]-TPP pode ser um agente interessante de direcionamento do tumor devido à baixa captação pelo fígado e pela dose bem baixa absorvida, de, aproximadamente, 0,036 do corpo humano total...

Bromodomain4 inhibitor JQ1 inhibits the proliferation of Ph positive acute lymphocytic leukemia cells and its mechanism / 白血病·淋巴瘤

Objective To observe the effect of bromodomain4 (brd4) inhibitor JQ1 on proliferation inhibition and apoptosis of Ph positive acute lymphocytic leukemia (Ph+ ALL) cells, and to explore the influence on the expression of brd4 and its downstream genes (myc and p53), and the reverse effect on bcr-abl.Methods Different concentrations of JQ1 were used on SUP-B15 cells.The proliferation inhibition rate was detected by MTT, the apoptosis rate was determined by flow cytometry (FCM), and the expressions of bcr-abl mRNA, brd4 mRNA, myc mRNA and p53 mRNA were detected by real-time fluorescent quantitative PCR (RT-PCR).Results Different concentrations of JQ1 inhibited SUP-B15 cells proliferation and induced cell apoptosis.The apoptosis rate was significantly increased compared with that in control group with a time-dose dependent manner.Median inhibitory concentration at 72 h was 1.0 pmol/L.At the same time, JQ1 decreased the transcription levels of bcr-abl mRNA, brd4 mRNA and myc mRNA, and increased the transcription level of p53 mRNA.Conclusions As a brd4 inhibitor, JQ1 can decrease the expression of brd4 to affect the expression of its downstream genes myc and p53, meanwhile, it can change the over expression of bcr-abl to suppress the proliferation of Ph+ ALL cells and induce apoptosis.

Effects of Goal-directed Volume Therapy on the Intracranial Pressure and the Balance of Cerebral Oxygen Consumption and Supply in Selective Neurosurgery / 华中科技大学学报(医学版)

Objective To investigate the effects of goal‐directed volume therapy (GDVT )on the intracranial pressure(ICP) and the balance of cerebral oxygen consumption and supply in selective neurosurgery. Methods Twenty‐four patients sched‐uled for intracranial tumor resection were randomly divided into 2 groups:conventional fluid management group (group C ,n=12) and GDVT group(group G ,n=12). Patients in group C received introperative fluid transfusion according to classical fluid management strategies while those in group G received GDT according to stroke volume variation (SVV) ,guided by Flotrac‐Vigileo system.Mean arterial pressure(MAP) ,heart rate(HR) ,cardiac index(CI) ,ICP ,SVV and jugular bulb oxygen saturation (SjvO2 )were recorded before the anesthesia induction(T1 ) ,at the moment of intubation(T2 ) ,at the moment of opening the hard meninges(T3),1hafteropeningthehardmeninges(T4),andattheendofthesurgery(T5).Thecerebraloxygenextractionra‐tio(CERO2 )was calculated. The duration of surgery ,crystalloid volume ,colloid volume ,blood transfusion volume ,urinary output and bleeding volume were recorded as well.Results The colloid transfusion volume ,the total fluid transfusion volume and uri‐nary output were significantly increased in group G when compared with those in group C (P0.05).Conclusion Goal‐directed fluid therapy optimizes the cardiac preload without increasing the ICP in selective neurosurgery ,and it also improves the balance of cerebral oxygen con‐sumption and supply.

Chemosensitivity and angiogenic potency of pre-B acute lymphoblastic leukemia cell line Sup-B15 / 中华实用儿科临床杂志

Objective It has been reported that Ik6 overexpression is associated with poor outcome of childhood pre-B acute lymphoblastic leukemia and Sup-B15 cell line is Ik6 positive.There were fewer studies on the Sup-B15 in the country,so the aim of this research is to explore chemosensitivity and angiogenic potency of pre-B acute lymphoblastic leukemia cell line Sup-B15 associated with Ik6 positive expression through making a comparison between Sup-B15 and Nalm-6 cell line.Methods The Ik6 mRNA and protein expression were detected by nested reverse transcription polymearse chain reaction and Western blot.The effect of vincristine,daunorubicin,L-asparaginase and dexamethasone on the proliferation of cells was measured by using CCK-8 assay.The migration and invasion of cells were detected by transwell assay and mRNA expression of angiogenesis genes (VEGF,Flt-1,PlGF,IGF-1,Ang1 and Ang2) was measured by real-time PCR.Results No expression of Ik6 was detected in Nalm-6 cell line.Compared with Nalm-6,Sup-B15 cell line had a lower rate of growth.The 4 drugs could inhibit the proliferation of cells in a dose-and time-depen-dence manner.Sup-B15 was more sensitive to daunorubicin,L-asparaginase and dexamethasone,and the folds of respective IC50 value were 9.5,1.1 and 1.5.But Sup-B15 was more resistant to vincristine than Nalm-6.The result of transwell assay showed that less Sup-B15 cells transmigrated to the lower chamber.A significant lower expression level of angiogenesis genes was detected in Sup-B15 cells.Conclusion These findings suggest that Sup-B15 is more sensitive to chemotherapy and less angiogenic compared with Nalm-6.

04-1Fangotherapy, a body-friendly treatment to use hot spring water for health promotion / 日本温泉気候物理医学会雑誌

Fangotherapy is one of four medical treatments used under a medical doctor’s supervision at a hot spring. This treatment is conducted in Europe, especially in Italy, using peloids maturated with natural hot spring water. The maturated peloids have factors of concentrated hot spring and biological extract -glycolipids- from thermophilic algae. <BR>  There are many kinds of hot springs in Japan, but they are almost always used for “taking a bath” only. Our research focused on Fango found in Abano Italy, and modified into “Japanese style Fango” made with maturated peloids by hot spring water. <BR><b>Methods: </b>The original Japanese Fango, which we made in a hot spring in Japan, has been named Biofango^®. The original and first Biofango^® was made from the Sanrakuen Hotel’s hot spring water in Toyama, and treated in the hotel as in the Abano style. The benefits of Biofango^® were checked using the following methods;<BR>1.　Hyperthermia and some medical effects were checked under treatment with maturated peloids, and the effects were compared with hot spring water only and with boiled tap water. <BR>2.　The double-blind method was used comparing Biofango^® (True Fango) and imitation Fango. Two kinds of Fango were made using either hot spring water or hot tap water, and some medical effects were checked. After treatment of Fangotherapy, a medical questionnaire was provided for each test subject.<BR><b>Results: </b>Fango (Biofango^®) is the best treatment among three bathing methods for keeping normal responses of blood flow and blood pressure at the thigh, and for keeping good thermal effects on the body, especially for the back of the body after 50 min. <BR>  The results of the double-blind method, deep body temperature increase and diastolic blood pressure decrease in True Fango showed a significant difference. Pulse increase and SIV decrease in True Fango shows a reduced load on the vessel, while still showing a high thermal effect. Functions of the body showed an improved friend in True Fango, according to the questionnaire survey.<BR><b>Conclusion: </b>Traditional use of hot spring water in Japan was hot spring bathing in the mainstream. But, according to these results, Fango is the best method for a body-friendly treatment by hot spring water. Further, the questionnaire about body functions after Fango treatment shows that the hot spring Fango (True Fango) is more effective than hot tap water Fango (imitation Fango).<BR>  In Italy, glycolipids from thermophilic algae are an important factor for reducing inflammation by Fango therapy. Growth of thermophilic algae also has been confirmed in Fango maturation in Japan, and was cultured in the laboratory. We also found such glycolipids from Japanese algae, and have evidence, <i>in situ</i>, of the glycolipids remaining between particles of peloids. In the future, Biofango^® should have a useful biological factor similar to Abano Fango for treatment.

A Case of Surgical Revascularization for Abdominal Angina / 日本心臓血管外科学会雑誌

A 68-year-old woman with multiple gastric ulcers was admitted to our hospital due to post-prandial abdominal pain. Multirow detector computed tomography (MDCT) showed severe stenoses of both the celiac trunk and superior mesenteric artery (SMA) ; therefore, we decided to operate based on the presumed diagnosis of abdominal angina. We bypassed the stenoses using a saphenous vein graft from the right external iliac artery to the SMA, distal to the stenosis. The patient was symptom-free postoperatively. In summary, this case of abdominal angina was accurately evaluated preoperatively with MDCT and the flow meter^®. Thereafter, a focal stenosis in the superior mesenteric artery was successfully treated with an external iliac-SMA bypass using a saphenous vein graft.

Prevalence of preoperative malnutrition and application of nutrition support among gastrointestinal cancer patients in Beijing / 中华临床营养杂志

ObjectiveTo investigate the prevalence of preoperative malnutrition and nutrition support among gastrointestinal cancer patients.MethodsA retrospective study was conducted based on the nutritional status and nutrition support of 336 gastrointestinal cancer patients who received elective radical surgery in Peking Union Medical College Hospital from April to December 2009.ResultsMalnutrition was found in 34.6％ gastric cancer patients,23.8 ％ colorectal cancer patients,and 23 ％ esophageal and cardiac cancer patients.The patients with worse nutritional status were given longer duration of nutrition support and higher energy intake.Conclusion Malnutrition occurs in gastrointestinal cancer patients,yet sometimes treated with inappropriate nutrition support.

New Anticoagulation Control for Toyobo-LVAS Using the CoaguChek XS^® / 日本心臓血管外科学会雑誌

Aggressive anticoagulation therapy is necessary when Toyobo-LVAS is used for long-term treatment of severe heart failure. However, it is necessary to regulate it carefully if there is a hemorrhagic complication due to thromboembolism, but repeated blood testing is painful. We compared simple measurement with the CoaguChek XS^® with the conventional blood testing method. The correlation coefficient was 0.916, and the regression line was <i>Y</i>=0.8027<i>X</i>+0.3399. In addition, drawing blood using the CoaguChek XS^® was very effective in the reported pain reduction in patients.

Apical gaps after apicoectomy procedures performed on teeth filled with gutta-percha or ResilonTM

Aim: This ex vivo study compared, under scanning electron microscopy (SEM), the marginal adaptation ofroot canal obturation with either ResilonTM or gutta-percha cones following root-end resection. Methods:Thirty human single-rooted teeth with fully formed apices were collected and decoronated. The root canalswere instrumented up to a size 45 taper .04 and obturated with laterally condensed gutta-percha (Group 1;n=15) or ResilonTM (Group 2; n=15). AH Plus sealer was used in both groups. After 48-h storage in saline, theapical 3 mm of each root were resected with a water-cooled high-speed plain fissure #170L carbide bur.Epoxy resin replicas of the resected root ends were examined by SEM. The total area of apical gap in eachreplica was measured using UTHSCSA ImageTool software. Data were analyzed statistically by the Mann-Whitney U-test (á=5%). Results: The mean area of apical gap in groups 1 and 2 was 0.0042 mm2 and 0.0015mm2, respectively, with no statistically significant difference (P = 0.83). Conclusions: The type of materialdid not influence at the apical adaptation of root canal obturation after apicoectomy, and the misfit may berelated to anatomic factors.

Efeito de um agente primer e de ciclos térmicos para cocção de porcelana na resistência de união adesiva entre alumina e cimento resinoso / Effect of a primer agent and thermal cycles for porcelain firing on the bond strength of resin cement to alumina

Coroas cerâmicas apoiadas sobre infra-estruturas de alumina densamente sinterizada configuram-se como excelentes opções para a reabilitação protética em casos de exigência estética, contudo, o aumento do conteúdo cristalino inviabiliza seu condicionamento por ácidos deixando a maneira ideal de cimentá-las ainda desconhecida. Coroas Procera AllCeram apresentam, em sua face interna, micro irregularidades interessantes ao embricamento e adesão resinosa, dispensando manobras de condicionamento. Objetivo: O objetivo deste trabalho foi avaliar a influência de elevadas temperaturas (500ºC à 950ºC) necessárias à cocção da porcelana de revestimento, na textura superficial da alumina, bem como o papel de um agente primer (Ivoclar Vivadent) na força de adesão entre alumina e cimento resinoso. Material e métodos: Sessenta (60) cilindros de alumina (3,5mm X 16mm) com rugosidade superficial idêntica à dos copings Procera foram divididos em quatro grupos (n=15). Grupo 1): Espécimes não submetidos a variação térmica, sendo G1a Sem aplicação do primer e G1b Com aplicação do primer e Grupo 2): Espécimes submetidos aos ciclos térmicos para cocção da porcelana feldspática, sendo G2a Sem aplicação do primer e G2b Com aplicação do primer. Sobre os cilindros aplicou-se porção do cimento resinoso químico MultiLink Ivoclar. Os espécimes foram levados a uma máquina de ensaios Universal para teste de cisalhamento a uma velocidade de 0.5mm/min e os dados submetidos à análise de variância a um critério e teste de comparações múltiplas de Tukey. Resultados: A força de adesão para cada um dos grupos foi: G1a = 2.468 MPa; G1b = 4.265 MPa; G2a = 2.339MPa e G2b = 4.185 MPa. Diferenças significantes foram observadas entre os grupos: G1a X G1b; G1a X G2b; G1b X G2a e G2a X G2b. Conclusões: Ciclos térmicos não produziram alterações na micro-estrutura superficial da alumina, tampouco comprometeram sua adesão ao cimento. O agente primer aumentou a força de união entre alumina e cimento resinoso...

High-strength alumina based ceramic crowns are widely used in dentistry due to their favorable esthetic, however, the large amount of crystalline contents jeopardizes their acid etching property and the ideal luting remains unclear. Procera AllCeram restorations exhibits on their intaglio surface micro irregularities optimizing the bonding to resin, with no need for additional conditioning procedures. Purpose: The aim of the present study was to evaluate the influence of high thermal cycles (500ºC to 950ºC) needed to porcelain firing on alumina's intaglio surface, as well as, the role of a primer agent (Ivoclar Vivadent) on shear bond strength between alumina and resin cement. Material and Methods: Sixty alumina cylinders (3,5mm X 16mm) with intaglio roughness of the Procera AllCeram copings were randomly divided into four groups (n=15). Group 1) Samples no submitted to thermal cycles variation, were G1a - no primer application and G1b - primer treated and Group 2: Samples submitted to thermal feldspathic porcelain firing cycles, were G2a - specimens no primer treated and G2b - primer treated specimens. Over the cylinders top a self-cure resin cement (Multilink Ivoclar) portion was applied. The specimens were loaded to failure in shear mode using a universal testing machine at a crosshead speed of 0,5mm/min. Data were analyzed with one-way analysis of variance and Tukey's multiple comparison test. Results: The shear bond strength for each group was: G1a = 2.468 MPa; G1b = 4.265 MPa; G2a = 2.339 MPa e G2b = 4.185 MPa. Significant difference was found between the groups G1a X G1b; G1a X G2b; G1b X G2a e G2a X G2b. Conclusions: Thermal cycles did not change alumina's surface micro structure, besides did not compromised it's bonding strength to resin cement. Primer agent enhanced shear bond strength between alumina and resin cement. Luting agent's cohesive fractures were observed only in some primer treated specimens.