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1.
Int J Surg Case Rep ; 76: 240-246, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33053481

RESUMO

INTRODUCTION: Pancreatoduodenectomy (PD) after gastrectomy requires more attention during surgery than ordinary PD due to anatomical variation with different types of gastrointestinal anastomoses, the complication of anatomical dissection, and the extent of adhesions present. Herein, we describe the PD strategies we used in three patients who strategy for three patients who had previously undergone distal gastrectomy for gastric cancer treatment. DISCUSSION: Generally, reconstruction following PD in patients who have undergone a prior Billroth I reconstruction is simple, as there is no previous afferent loop. By comparison, reconstruction after a Billroth II or R-Y reconstruction requires special consideration of the point of circulation and length of the remnant intestine used for pancreaticojejunostomy, choledochojejunostomy or gastrojejunostomy. CONCLUSION: There is no consensus regarding the best method for performing PD and reconstruction in patients with a prior history of gastrectomy. The appropriateness of using the existing afferent loop for reconstruction depends on whether the jejunum is of sufficient length for bile duct and pancreatic anastomosis. Regardless of the approach used, it is necessary to avoid excessive tension during reconstruction. Based on our experience and previous studies published in the English literature, we propose that reconstruction needs to be considered on a case-by-case basis.

2.
Int J Surg Case Rep ; 72: 17-21, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32506022

RESUMO

INTRODUCTION: Secondary aorto-duodenal fistula (sADF) is a complication of abdominal aorta artificial blood vessel replacement that often leads to death. However, an optimal operative method has not yet been established. We describe a patient who underwent artificial blood vessel reimplantation and duodenectomy after endovascular aneurysmal repair (EVAR) with positive outcomes. PRESENTATION OF CASE: An 84-year-old man underwent artificial blood vessel replacement in 2015. In September 2016, he visited our emergency department and was diagnosed with sADF based on computed tomography. Urgent EVAR was performed, followed by duodenal segmental resection on the next day without opening the syringeal part to minimize the pollution of the operative field. Artificial blood vessel reimplantation and omental flap transposition were performed. As of 2020, about 3 years after surgery, there has been no relapse of the infection. DISCUSSION: Using our novel operative method, we can minimize exposure of the artificial blood vessel and surrounding tissue to intestinal juice and pus. We believe that this reduces the risk of postoperative artificial blood vessel reinfection. CONCLUSION: Controlling bleeding by EVAR and resection of the duodenum and artificial blood vessels as a group without opening the syringeal part can contribute to positive long-term results as this method minimizes the pollution of the duodenectomy surgical field.

3.
Int J Surg Case Rep ; 71: 163-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454453

RESUMO

INTRODUCTION: In case of gastrointestinal diverticula, the duodenal type is quite frequent; duodenum is the second most common site for diverticula following the colon (Glener et al., 2016). However, duodenal diverticular perforation is rare, so the appropriate surgical treatment for this condition is yet unclear (Simoes et al., 2014). This literature has been written in line with the SCARE criteria (Agha et al., 2018). PRESENTATION OF CASE: A 94-year-old woman emergently presented to our department with diffuse abdominal tenderness and guarding, indicating pan-peritonitis. Computed tomography revealed pneumoretroperitoneum; Therefore, gastrointestinal perforation was suspected. Emergency surgery was performed; we detected the perforated diverticulum located at the posterior wall of the duodenum with accompanying inflammation. Considering the location, postoperative leakage, and the patient's advanced age, we placed trans-section on duodenal wall against the lesion and resected the diverticulum, The lumen was then manually sutured from within. The anterior wall was closed using linear staplers. The patient recovered uneventfully and was discharged 24 days after surgery. DISCUSSSIONS: As perforated duodenal diverticulum is rare, the ideal management is unclear. Several studies mention various surgical procedures. However, actual treatment varies based on the patient's situation and surgeon's assessment. Almost all cases that require surgery present emergently; therefore, simpler and more effective treatment methods are required (Simoes et al., 2014; Philip et al., 2019; Fujisaki et al., 2014). CONCLUSION: We used a unique surgical technique; intraduodenal suture for perforated diverticulum. This technique can be a feasible alternative for managing this condition.

4.
Nanomaterials (Basel) ; 10(1)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936136

RESUMO

Polydopamine (PDA)-a known adhesive coating material-was used herein to strongly immobilize a Pt-particle catalyst on an acrylonitrile-butadiene-styrene copolymer (ABS) substrate. Previous studies have shown that the poor adhesion between Pt particles and ABS surfaces is a considerable problem, leading to low catalytic durability for H2O2 decomposition during contact-lens cleaning. First, the ABS substrate was coated with PDA, and the PDA film was evaluated by X-ray photoelectron spectroscopy. Second, Pt particles were immobilized on the PDA-coated ABS substrate (ABS-PDA) using the electron-beam irradiation reduction method. The Pt particles immobilized on ABS-PDA (Pt/ABS-PDA) were observed using a scanning electron microscope. The Pt-loading weight was measured by inductively coupled plasma atomic emission spectroscopy. Third, the catalytic activity of the Pt/ABS-PDA was evaluated as the residual H2O2 concentration after immersing it in a 35,000-ppm H2O2 solution (the target value was less than 100 ppm). The catalytic durability was evaluated as the residual H2O2 concentration after repeated use. The PDA coating drastically improved both the catalytic activity and durability because of the high Pt-loading weight and strong adhesion among Pt particles, PDA, and the ABS substrate. Plasma treatment prior to PDA coating further improved the catalytic durability.

5.
Case Rep Oncol ; 12(2): 671-680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572157

RESUMO

Conversion surgery has been reported but few cases have undergone surgical R0 resection after second-line chemotherapy. We report a case of an unresectable locally advanced gastric cancer in a patient who finally underwent the operation (R0) after second-line chemotherapy. The 77-year-old male was diagnosed with gastric cancer (cT4 [SI; Skin, Liver] N0M0 c Stage IIIA) with invasion to the skin of the abdominal wall, and chemotherapy was initially performed because of his poor performance status and due to the large defect in the abdominal wall that might occur if an operation was performed. Partial response (PR) was observed after S-1+CDDP (SP) therapy, which was then stopped after which progressive disease (PD) was observed. Ramucirumab+Paclitaxel (RAM/PTX) therapy was chosen as second-line therapy, and PR was obtained again, following which total gastrectomy was performed (D2 dissection of lymph nodes, Roux-en-Y reconstruction, and combined resection of the partial skin and the affected region of the liver). At 30 months postoperatively, no recurrence has occurred and the patient is alive after the operation without chemotherapy.

6.
Gan To Kagaku Ryoho ; 46(6): 1057-1059, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273175

RESUMO

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. Endoscopic metallic stent placement and angiogenesis inhibitor administration carry the risk of gastrointestinal perforation. The outcomes of patients who undergo endoscopic placement of metallic stents during RAM treatment have not yet been fully assessed. A 60's man was diagnosed with advanced esophagogastric junction cancer(por) with Virchow's lymph node metastases. His tumor was classified as cT4a(SE), N1(#1), M1, stage Ⅳ. He received chemotherapy, but the size of the primary tumor and metastases increased. After stenting for gastric outlet obstruction, he received a paclitaxel(PTX)plus RAM regimen as third-line treatment. Because of CTCAE Grade 2 peripheral neuropathy, PTX was discontinued after 10 courses. For 11 months, tumor control without adverse events was maintained. The patient was then switched to CPT-11 as fourth-line treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Gástricas , Anticorpos Monoclonais Humanizados , Junção Esofagogástrica , Humanos , Masculino , Stents , Neoplasias Gástricas/terapia , Ramucirumab
7.
Anticancer Res ; 39(6): 3207-3211, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177169

RESUMO

BACKGROUND/AIM: Right aortic arch (RAA) is a rare abnormality of the aortic arch that forms a vascular ring. Oesophageal cancer (EC) accompanied with RAA is even rarer, and in such cases, it is very important to understand the anatomical structure in the upper mediastinum in order to perform a safe and curative operation. PATIENTS AND METHODS: A 67-year-old man who presented with pharyngeal discomfort was admitted to our hospital. Further examinations revealed advanced thoracic EC accompanied with RAA and aortic diverticulum. RESULTS: After neoadjuvant chemotherapy, we successfully and safely performed thoracoscopic oesophagectomy and lymphadenectomy using the prone positioning. CONCLUSION: There exist only a few reports of thoracoscopic oesophagectomy for EC with RAA. Sufficient preoperative preparation and sharing an adequate strategy for the surgical approach with the surgical team are definitely necessary. Although the thoracoscopic approach for EC with RAA is useful, more considerations are needed for some issues.


Assuntos
Aorta Torácica/anormalidades , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Posicionamento do Paciente/métodos , Decúbito Ventral , Toracoscopia , Idoso , Aorta Torácica/diagnóstico por imagem , Aortografia/métodos , Quimioterapia Adjuvante , Angiografia por Tomografia Computadorizada , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Humanos , Excisão de Linfonodo , Masculino , Terapia Neoadjuvante , Resultado do Tratamento
8.
Nanomaterials (Basel) ; 9(3)2019 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-30832399

RESUMO

In a previous study, Pt nanoparticles were supported on a substrate of acrylonitrile⁻butadiene⁻styrene copolymer (ABS) to give the ABS surface catalytic activity for H2O2 decomposition during contact lens cleaning. Although the Pt-particle/ABS catalysts exhibited considerably high specific catalytic activity for H2O2 decomposition, the catalytic activity decreased with increasing numbers of repeated usage, which meant the durability of the catalytic activity was low. Therefore, to improve the catalytic durability in this study, we proposed two types of pretreatments, as well as a combination of these treatments before supporting Pt nanoparticles on the ABS substrate. In the first method, the ABS substrate was etched, and in the second method, the surface charge of the ABS substrate was controlled. A combination of etching and surface charge control was also applied as a third method. The effects of these pretreatments on the surface morphology, surface chemical composition, deposition behavior of Pt particles, and Pt loading weight were investigated by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), cross-sectional SEM, and inductively coupled plasma atomic emission spectroscopy (ICP-AES), respectively. Both etching and controlling the surface charge effectively improved the catalytic durability for H2O2 decomposition. In addition, the combination treatment was the most effective.

9.
Surg Endosc ; 32(9): 4011-4016, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29915985

RESUMO

BACKGROUND: Billroth I reconstruction is a means of anastomosis that is widely performed after surgical resection for distal gastric cancer. Interest has grown in totally laparoscopic gastrectomy, and several methods for totally laparoscopic performance of Billroth I reconstruction have been reported. However, the methods are cumbersome, and postoperative complications such as twisting at the site of anastomosis and obstruction due to stenosis have arisen. We developed an augmented rectangle technique (ART) by which the anastomosis is created laparoscopically with the use of three automatic endoscopic linear staplers, and the resulting anastomotic opening is wide and less likely to become twisted or stenosed. The technical details of our ART-based Billroth I anastomosis are presented herein along with results of the procedure to date. METHODS: The technique was applied in 160 patients who underwent totally laparoscopic distal gastrectomy for gastric cancer between December 2013 and August 2017. Clinicopathological data, surgical data, and postoperative outcomes were analyzed. RESULTS: During surgery, there were no troubles associated with gastrointestinal reconstruction and there was no transition to laparotomy. There were no postoperative complications, including suture failure and stenosis, associated with the gastrointestinal reconstruction, and the average postoperative hospital stay was 12 days. CONCLUSION: Totally laparoscopic ART-based Billroth I reconstruction is both feasible and safe. We expect this technique to contribute to the spread of safe totally laparoscopic surgery for gastric cancer.


Assuntos
Gastrectomia/métodos , Gastroenterostomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Masculino
10.
Nanomaterials (Basel) ; 7(9)2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28832553

RESUMO

A container used in contact lens cleaning requires a Pt plating weight of 1.5 mg for H2O2 decomposition although Pt is an expensive material. Techniques that decrease the amount of Pt are therefore needed. In this study, Pt nanoparticles instead of Pt plating film were supported on a substrate of acrylonitrile-butadiene-styrene copolymer (ABS). This was achieved by the reduction of Pt ions in an aqueous solution containing the ABS substrate using high-energy electron-beam irradiation. Pt nanoparticles supported on the ABS substrate (Pt-particle/ABS) had a size of 4-10 nm. The amount of Pt required for Pt-particle/ABS was 250 times less than that required for an ABS substrate covered with Pt plating film (Pt-film/ABS). The catalytic activity for H2O2 decomposition was estimated by measuring the residual H2O2 concentration after immersing the catalyst for 360 min. The Pt-particle/ABS catalyst had a considerably higher specific catalytic activity for H2O2 decomposition than the Pt-film/ABS catalyst. In addition, sterilization performance was estimated from the initial rate of H2O2 decomposition over 60 min. The Pt-particle/ABS catalyst demonstrated a better sterilization performance than the Pt-film/ABS catalyst. The difference between Pt-particle/ABS and Pt-film/ABS was shown to reflect the size of the O2 bubbles formed during H2O2 decomposition.

11.
J Med Invest ; 63(3-4): 270-3, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27644570

RESUMO

We devised a method for confirming the position of mesh placed during transabdominal preperitoneal repair (TAPP) of an inguinal hernia. The preperitoneum is sufficiently detached, and the mesh is fixed in place as usual. Before completely closing the peritoneum, pressure is applied from outside the body and inside the abdominal cavity to remove as much air as possible from the detached preperitoneum; the peritoneum is then sutured using a V-Loc(TM) closure device so that it does not constrict. By releasing the pressure all at once, the airtightness of the preperitoneum is maintained, and the position of the mesh can be observed through the translucent peritoneum. This method, called Mesh-Airtight-Preperitoneum (MAPP), could become widely used as a simple technique for confirming mesh position in TAPP. J. Med. Invest. 63: 270-273, August, 2016.


Assuntos
Hérnia Inguinal/cirurgia , Peritônio/cirurgia , Telas Cirúrgicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Sutura
12.
J Med Invest ; 63(1-2): 68-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27040056

RESUMO

The purpose of this study was to investigate the oncologic outcomes of laparoscopic distal gastrectomy (LDG) for advanced gastric cancer (AGC). Between April 2003 and March 2014, LDG was performed for 392 patients, 91 patients (23.2%) had histopathologically diagnosed AGC beyond T2 depth. The clinicopathological features, postoperative outcomes, mortality, morbidity, recurrence rate, and survivals of those patients were reviewed. The TNM stages of the tumor were IB in 26 patients (28.5%), IIA in 20 (21.9%), IIB in 18 (19.7%), IIIA in 13 (14.2%), IIIB in 6 (6.5%), IIIC in 6 (6.5%), and IV in 2 (2.1%). Major morbidity occurred in 14 patients (15.3%), with no postoperative mortality. Median follow-up was 24.5 months; 10 patients developed recurrence during the follow-up period, and 10 patients died, including 6 cancer deaths. The 5-year overall and disease-free survival rates were 76.8% and 72.6%, respectively. By stage, OS/DFS was 92.3%/91.8% in stage IB, 85.4%/85.4% in stage II, and 49.3%/26.9% in stage III. Oncologic outcomes were good in patients with AGC, especially with stage IB-IIB, who underwent LDG. LDG appears to be an effective approach for treating stage IB and II gastric cancer.


Assuntos
Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
13.
Asian J Endosc Surg ; 9(3): 179-85, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27122447

RESUMO

INTRODUCTION: We evaluated 3-D CT imaging for preoperative classification of the left gastric artery and vein in patients with early gastric cancer and estimated its clinical benefit. METHODS: Between April 2009 and March 2014, 279 patients underwent preoperative 3-D CT using a 64-row multi-detector CT scanner, followed by laparoscopy-assisted distal gastrectomy. The 3-D CT images of the arterial and portal phases were reconstructed and fused. The operative outcomes were compared between patients who had not undergone 3-D CT (2007-2008) and who had undergone 3-D CT (2009-2011). RESULTS: According to Adachi's classification, the numbers of type I, II, III, IV, V, and VI arterial patterns were 253, 15, 1, 3, 3, and 1, respectively. Three cases could not be classified. According to the Douglass classification, the left gastric vein flowed into the portal vein, splenic vein, junction of the portal vein and splenic vein, and left branch of the portal vein in 119, 111, 36, and 5 patients, respectively. The left gastric vein could not be visualized in six patients, and two patients could not be classified. In addition, the relation was absent for an Adachi type I vein and one of the "other" types of veins. The total operative time was significantly shorter with 3-D CT than without it (P = 0.01), and the degree of lymph-node dissection was significantly higher (P = 0.01). Inflammatory parameters and operative morbidity tended to decrease with 3-D CT. CONCLUSION: Three-dimensional CT is a useful modality to visualize the vessel anatomy around the stomach, and it improves clinical effectiveness and reduces the invasiveness of surgery.


Assuntos
Gastrectomia , Imageamento Tridimensional , Laparoscopia , Tomografia Computadorizada Multidetectores/métodos , Cuidados Pré-Operatórios/métodos , Neoplasias Gástricas/cirurgia , Estômago/irrigação sanguínea , Adulto , Idoso , Idoso de 80 Anos ou mais , Artéria Celíaca/diagnóstico por imagem , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estômago/diagnóstico por imagem , Estômago/cirurgia , Resultado do Tratamento , Veias/diagnóstico por imagem
14.
Gan To Kagaku Ryoho ; 42(11): 1431-4, 2015 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-26602406

RESUMO

A 61-year-old man with advanced sigmoid colon cancer was admitted to our hospital. Abdominal computed tomography (CT) revealed locally advanced sigmoid colon cancer, with suspected invasion of the bladder and small intestine. The clinical stage of the disease was T4b, N1, M0, and Stage III a, with wild-type KRAS expression. A transverse colostomy was performed because of the presence of a bowel obstruction. The patient received 4 courses of Leucovorin, 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI). The size of the tumor and lymph nodes decreased noticeably after chemotherapy and laparoscopic high anterior resection with lymph node dissection. During this phase, the pathological stage of the disease was ypT0, N0, and Stage 0(no viable carcinoma cells, Grade 3). This result suggested that preoperative FOLFOXIRI chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo Sigmoide/tratamento farmacológico , Biópsia , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo Sigmoide/patologia , Neoplasias do Colo Sigmoide/cirurgia , Tomografia Computadorizada por Raios X
15.
Gan To Kagaku Ryoho ; 42(5): 637-40, 2015 May.
Artigo em Japonês | MEDLINE | ID: mdl-25981663

RESUMO

In our hospital, a clinical trial on the effects of preoperative 2-week S-1 administration for advanced gastric cancer is being conducted. A7 5-year-old man presented to our hospital with a type 2 tumor(poorly differentiated adenocarcinoma)in the pyloric antrum. Subpyloric lymph node enlargement and a c-T2(MP), N1, M0, Stage II A tumor (according to the gastric cancer handling agreement, 14th edition)were diagnosed, and S-1(100mg/day)was subsequently administered for 14 days. On day 15, we performed laparoscopy-assisted distal gastrectomy, with D2 dissection. Analysis of the resected specimen, ie the primary tumor and metastatic lymph nodes, confirmed the effect of the treatment as Grade 2, and revealed a type 2 gastric cancer of 30×20mm in size; this tumor was downstaged to yp-T1b(SM), N1, Stage I B. No adverse events associated with perioperative S-1 were observed, and the postoperative course was good. At the latest follow-up(6 years after treatment), no recurrence was observed.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Adenocarcinoma/cirurgia , Idoso , Combinação de Medicamentos , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
16.
PLoS One ; 8(3): e50121, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23505410

RESUMO

The human α1A voltage-dependent calcium channel (Cav2.1) is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C)-tail contains a small poly-glutamine (Q) tract, whose length is normally 4∼19 Q, but when expanded up to 20∼33Q, the tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6). A recent study has shown that a 75-kDa C-terminal fragment (CTF) containing the polyQ tract remains soluble in normal brains, but becomes insoluble mainly in the cytoplasm with additional localization to the nuclei of human SCA6 Purkinje cells. However, the mechanism by which the CTF aggregation leads to neurodegeneration is completely elusive, particularly whether the CTF exerts more toxicity in the nucleus or in the cytoplasm. We tagged recombinant (r)CTF with either nuclear-localization or nuclear-export signal, created doxycyclin-inducible rat pheochromocytoma (PC12) cell lines, and found that the CTF is more toxic in the cytoplasm than in the nucleus, the observations being more obvious with Q28 (disease range) than with Q13 (normal-length). Surprisingly, the CTF aggregates co-localized both with cAMP response element-binding protein (CREB) and phosphorylated-CREB (p-CREB) in the cytoplasm, and Western blot analysis showed that the quantity of CREB and p-CREB were both decreased in the nucleus when the rCTF formed aggregates in the cytoplasm. In human brains, polyQ aggregates also co-localized with CREB in the cytoplasm of SCA6 Purkinje cells, but not in other conditions. Collectively, the cytoplasmic Cav2.1-CTF aggregates are sufficient to cause cell death, and one of the pathogenic mechanisms may be abnormal CREB trafficking in the cytoplasm and reduced CREB and p-CREB levels in the nuclei.


Assuntos
Canais de Cálcio/metabolismo , Citoplasma/metabolismo , Animais , Canais de Cálcio/química , Canais de Cálcio/genética , Canais de Cálcio/toxicidade , Morte Celular , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Doxiciclina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Espaço Intracelular/metabolismo , Sinais de Exportação Nuclear/genética , Sinais de Localização Nuclear/química , Sinais de Localização Nuclear/genética , Ligação Proteica , Transporte Proteico , Células de Purkinje/metabolismo , Células de Purkinje/patologia , Ratos
17.
Neuropathology ; 32(6): 595-603, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22393909

RESUMO

Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant neurodegenerative disorder caused by a small expansion of tri-nucleotide (CAG) repeat encoding polyglutamine (polyQ) in the gene for α(1A) voltage-dependent calcium channel (Ca(v) 2.1). Thus, this disease is one of the nine neurodegenerative disorders called polyQ diseases. The Purkinje cell predominant neuronal loss is the characteristic neuropathology of SCA6, and a 75-kDa carboxy-terminal fragment (CTF) of Ca(v) 2.1 containing polyQ, which remains soluble in normal brains, becomes insoluble in the cytoplasm of SCA6 Purkinje cells. Because the suppression of the brain-derived neurotrophic factor (BDNF) expression is a potentially momentous phenomenon in many other polyQ diseases, we implemented BDNF expression analysis in SCA6 human cerebellum using quantitative RT-PCR for the BDNF mRNA, and by immunohistochemistry for the BDNF protein. We observed significantly reduced BDNF mRNA levels in SCA6 cerebellum (n = 3) compared to controls (n = 6) (Mann-Whitney U-test, P = 0.0201). On immunohistochemistry, BDNF protein was only weakly stained in control cerebellum. On the other hand, we found numerous BDNF-immunoreactive granules in dendrites of SCA6 Purkinje cells. We did not observe similar BDNF-immunoreactive granules in other polyQ diseases, such as Huntington's disease or SCA2. As we often observed that the 1C2-positive Ca(v) 2.1 aggregates existed more proximally than the BDNF-positive granules in the dendrites, we speculated that the BDNF protein trafficking in dendrites may be disturbed by Ca(v) 2.1 aggregates in SCA6 Purkinje cells. We conclude that the SCA6 pathogenic mechanism associates with the BDNF mRNA expression reduction and abnormal localization of BDNF protein.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Cerebelo/metabolismo , Regulação da Expressão Gênica , RNA Mensageiro/biossíntese , Ataxias Espinocerebelares/metabolismo , Ataxias Espinocerebelares/patologia , Idoso , Idoso de 80 Anos ou mais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cerebelo/patologia , Citoplasma/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células de Purkinje/metabolismo , Células de Purkinje/patologia , Ataxias Espinocerebelares/genética
18.
J Nippon Med Sch ; 78(2): 84-95, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21551965

RESUMO

This study aimed to examine whether morphological changes during the early stage of treatment or indices of proliferation, apoptosis, or hormone receptors are reliable predictors of the hormonal response to uterus-preserving high-dose progestin therapy in patients with endometrial adenocarcinoma. Seven patients (5 good responders and 2 poor responders) with presumptive stage IA endometrial adenocarcinoma treated with 600 mg/day of medroxyprogesterone acetate were reviewed. Epithelial cell size and stromal area observable on microscopic examination of hematoxylin and eosin-stained sections, and immunostaining labeling indices for Ki-67 nuclear antigen, single-stranded DNA, estrogen receptor, and progesterone receptor were semiquantitatively analyzed before treatment and after 4, 8, 12, and 16 weeks of treatment using computer imaging programs. The mean ratio of cell size after 4 weeks of treatment to that before treatment in good responders was 3.83, whereas the ratios in the 2 poor responders were 1.08 and 0.98. The mean Ki-67 nuclear antigen labeling index before treatment was 37.2% for the 5 good responders but was 51.0% in the 2 poor responders. The indices of the poor responders remained high (20%-77%), even after 16 weeks of treatment; in contrast, the indices of the good responders were low (0.4%-7.3%) throughout the treatment period. No definitive differences in labeling indices for single-stranded DNA, estrogen receptor, or progesterone receptor were observed between good and poor responders or at different stages of treatment (p>0.05). In conclusion, a higher epithelial cell size ratio after 4 weeks of treatment in conjunction with lower Ki-67 nuclear antigen labeling indices could be a potential predictor of hormonal response.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Processamento de Imagem Assistida por Computador , Progestinas/administração & dosagem , Progestinas/uso terapêutico , Adenocarcinoma/sangue , Adulto , Antígeno Ca-125/sangue , Diferenciação Celular , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/sangue , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Membrana/sangue , Estadiamento de Neoplasias
19.
Eye Contact Lens ; 37(2): 85-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21252684

RESUMO

OBJECTIVES: Polyhexamethylene biguanide (PHMB) exhibits broad-spectrum antimicrobial activity and is included in multipurpose solutions for contact lenses as a disinfectant. Both cationic and hydrophobic features of PHMB are believed to support its association with microbial cell membranes through electrostatic and hydrophobic interactions. We now evaluated the effects of ionic and surfactant agents on the antimicrobial activity of PHMB. METHODS: The antimicrobial activity of PHMB (1 ppm) against various bacteria and fungi was measured with the stand-alone procedure (ISO 14729, 2001). The effect of NaCl as an ionic isotonic agent on such an activity was determined in comparison with that of propylene glycol as a nonionic isotonic agent. The effect of the nonionic surfactant Poloxamer 407 (Px407) was similarly examined in the absence or presence of NaCl. RESULTS: The antimicrobial activity of PHMB increased with time, being especially pronounced after 60 min. This activity was inhibited by NaCl in a concentration-dependent manner but was not affected by propylene glycol. Poloxamer 407 (4%) alone slightly increased the activity of PHMB toward Staphylococcus aureus and fungi. Although Px407 prevented the inhibitory effect of NaCl on PHMB activity against bacteria, it enhanced that observed with Candida albicans. CONCLUSIONS: The antimicrobial activity of PHMB was inhibited by adjustment of osmolality with the ionic agent NaCl but not by that with the nonionic agent propylene glycol. The surfactant Px407 exhibited complex effects on PHMB activity in the presence of NaCl. These findings indicate that the electrostatic interaction with the cell membrane is a dominant factor in the antimicrobial activity of PHMB.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Biguanidas/farmacologia , Fungos/efeitos dos fármacos , Anti-Infecciosos/antagonistas & inibidores , Biguanidas/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Poloxâmero/farmacologia , Propilenoglicol/farmacologia , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Tensoativos/farmacologia , Fatores de Tempo
20.
Eye Contact Lens ; 37(2): 57-60, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21252685

RESUMO

OBJECTIVES: Alexidine is a bis-biguanide disinfectant with two cationic active sites and hydrophobic ethylhexyl end groups, both of which are believed to support its association with microbial cell membranes through electrostatic and hydrophobic interactions. We evaluated the effects of tonicity-adjusting and surfactant agents on the antimicrobial activity of alexidine to assess its suitability as a disinfectant in multipurpose solutions for contact lenses. METHODS: The antimicrobial activity of alexidine (4.5 ppm) against various bacteria and fungi was measured with the stand-alone procedure (ISO 14729, 2001). The effect of NaCl as an ionic tonicity-adjusting agent on such activity was determined in comparison with that of propylene glycol as a nonionic tonicity-adjusting agent. The effect of the nonionic surfactant Poloxamer 407 (Px407) was similarly examined in the absence or presence of NaCl. RESULTS: Alexidine showed robust antimicrobial activity, with no organisms surviving after 1 hr. Antifungal activity was inhibited by NaCl in a concentration-dependent manner, whereas neither antibacterial nor antifungal activity was affected by propylene glycol. The activity of alexidine was not affected by Px407 (4%) alone but was attenuated by the combination of NaCl and Px407 with all microorganisms tested. CONCLUSIONS: The antifungal activity of alexidine was inhibited by adjustment of osmolality with the ionic agent NaCl but not by that with the nonionic agent propylene glycol. The surfactant Px407 reduced antimicrobial activity only in the presence of NaCl. These findings indicate that electrostatic and hydrophobic interactions with the microbial cell membrane are a key factor in the antimicrobial activity of alexidine.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Biguanidas/farmacologia , Fungos/efeitos dos fármacos , Anti-Infecciosos/antagonistas & inibidores , Biguanidas/antagonistas & inibidores , Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Poloxâmero/farmacologia , Propilenoglicol/farmacologia , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/farmacologia , Tensoativos/farmacologia
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