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1.
Pharmazie ; 78(11): 245-250, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38178284

ABSTRACT

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.


Subject(s)
Laxatives , Opioid-Induced Constipation , United States/epidemiology , Humans , Laxatives/adverse effects , Analgesics, Opioid/adverse effects , Constipation/chemically induced , Constipation/epidemiology , Magnesium/therapeutic use , Opioid-Induced Constipation/drug therapy , Pharmacovigilance
2.
Pharmazie ; 76(9): 437-443, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34481535

ABSTRACT

The aim of this study was to investigate the association between the incidence of Guillain-Barré syndrome (GBS) and seasonal influenza vaccines using the United States Vaccine Adverse Event Reporting System. Using multiple logistic regression analysis, we calculated the adjusted reporting odds ratio (ROR) of GBS cases associated with seasonal influenza vaccines administered from August 2018 to July 2019. Additionally, we analyzed the time-to-onset profile. The total number of adverse events reported following vaccination during this period was 43,235. Most of the GBS patients received a cell culture-based quadrivalent inactivated influenza vaccine (42.2%), quadrivalent inactivated influenza vaccine (26.6%), or high-dose trivalent inactivated influenza vaccine (15.6%). The adjusted ROR of seasonal influenza vaccines for GBS was 3.44 (2.40-4.95). The adjusted ROR of sex (male) (as reference female) and 0.5-59 years (as reference ≥ 60 years) were 1.90 (0.73-4.95) and 1.57 (0.88-2.78). Male sex and advanced age were not risk factors for GBS. The median duration of GBS was 9.5 (4.0-21.5) days. GBS following seasonal influenza vaccination developed mainly within 14 days and 42 days at most. In sex-stratified analyses, the median durations of GBS in females and males were 12.0 (8.3-28.5) and 5.0 (3.0-15.5) days (P = 0.050). Therefore, our findings indicate that the incidence of GBS is associated with seasonal influenza vaccines, and careful monitoring of GBS is required for up to 42 days, especially in the first 14 days. Moreover, GBS may occur slightly earlier in males than in females.


Subject(s)
Guillain-Barre Syndrome , Influenza Vaccines , Female , Guillain-Barre Syndrome/chemically induced , Guillain-Barre Syndrome/epidemiology , Humans , Incidence , Influenza Vaccines/adverse effects , Male , Seasons , United States/epidemiology , Vaccination/adverse effects
3.
Int J Colorectal Dis ; 36(2): 405-411, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33047209

ABSTRACT

PURPOSE: The aim of this study is to reveal the vascular branching variation in SFC (splenic flexure cancer) patients using the preoperative three-dimensional computed tomography angiography with colonography (3D-CTAC). METHODS: We retrospectively analyzed patients with SFC who underwent preoperative 3D-CTAC between January 2014 and December 2019. RESULTS: Among 1256 colorectal cancer (CRC) patients, 96 (7.6%) manifested SFC. The arterial branching from the superior mesenteric artery (SMA) was classified into five patterns, as follows: (type 1A) the left branch of middle colic artery (LMCA) diverged from middle colic artery (MCA) (N = 47, 49.0%); (2A) the LMCA diverged from the MCA and the accessory middle colic artery (AMCA) (N = 26, 27.1%); (3A) the LMCA independently diverged from the SMA (N = 16, 16.7%); (4A) the LMCA independently diverged from the SMA and AMCA (N = 3, 3.1%); (5A) only the AMCA and the LMCA was absent (N = 4, 4.1%). Venous drainage was classified into four patterns, as follows: (type 1V) the SFV flows into the inferior mesenteric vein (IMV) then back to the splenic vein (N = 50, 52.1%); (2V) the SFV flows into the IMV then back to the superior mesenteric vein (SMV) (N = 19, 19.8%); (type 3V) the SFV independently flows into the splenic vein (N = 3, 3.1%); (type 4V) the SFV is absent (N = 24, 25.0%). CONCLUSION: 3D-CTAC could reveal accurate preoperative tumor localization and vascular branching. These classifications should be helpful in performing accurate complete mesocolic excision and central vessel ligation for SFC.


Subject(s)
Colon, Transverse , Colonic Neoplasms , Colonic Neoplasms/diagnostic imaging , Computed Tomography Angiography , Humans , Imaging, Three-Dimensional , Retrospective Studies
4.
Pharmazie ; 74(10): 630-638, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31685091

ABSTRACT

The aim of this study was to clarify the community pharmacy-level factors related to experiences of and attitudes toward collaboration with medical and nursing home care facilities. We conducted a postal questionnaire survey of all pharmacies in Gifu, Japan, assessing the experiences and attitudes of supervising pharmacists regarding the following activities related to collaboration between medical facilities and nursing home care facilities: regional care meetings/service adjustment meetings, case discussion conferences, joint workshops/continuing education conferences, community service, information sharing through medical cooperation networks, and pharmacists accompanying physicians on home care visits. The factors significantly related to inter-professional collaboration were the family pharmacist guidance fee and the number of patients offered pharmaceutical care through cooperation with other medical facilities. Items on attitudes toward collaborating with other medical facilities showed similar results. Overall, policies that support inter-professional collaboration to create a foundation, establish mechanisms to facilitate collaboration, and identify collaborative activities that can be carried out at each pharmacy should be developed.


Subject(s)
Community Pharmacy Services/organization & administration , Nursing Homes/organization & administration , Female , Home Care Services , Humans , Japan , Male , Pharmacies , Pharmacists , Surveys and Questionnaires
5.
Pharmazie ; 74(5): 286-289, 2019 05 01.
Article in English | MEDLINE | ID: mdl-31109398

ABSTRACT

Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel ® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400-550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.


Subject(s)
Bromocriptine/chemistry , Bromocriptine/radiation effects , Chromatography, High Pressure Liquid , Color , Drug Stability , Lighting , Photolysis , Tablets/chemistry , Tablets/radiation effects , Temperature
6.
Pharmazie ; 73(9): 545-552, 2018 09 01.
Article in English | MEDLINE | ID: mdl-30223940

ABSTRACT

The aim of this study was to clarify the clinic-level factors related to experiences of and attitudes toward collaboration with community pharmacies. We conducted a postal questionnaire survey of all clinics in Gifu, Japan, assessing the experiences and attitudes of representative clinical staff regarding the following activities in collaboration with community pharmacists: regional care meetings/service adjustment meetings, case study conferences, joint workshops/continuing education conferences, community services, information sharing through medical cooperation networks, and accompanying community pharmacists during home care. The factors significantly related to experiences of joint workshops/continuing education conferences included home care visits (odds ratio [OR] 2.39) and a 100 % out-of-hospital prescription ratio (OR 4.80). In contrast, only home care visits were significantly associated with consideration of information sharing through medical cooperation networks and accompanying community pharmacists during home care (OR 2.06 and 11.91, respectively). Finally, the factors significantly associated with considering implementing case study conferences and joint workshops/continuing education conferences included home care visits (OR 4.64 and 2.98, respectively) and a 100% out-of-hospital prescription ratio (OR 4.64 and 6.38). Overall, having more opportunities to communicate with community pharmacists and other healthcare professionals appeared to facilitate clinics' consideration of collaboration with community pharmacies, along with actual experiences.


Subject(s)
Community Pharmacy Services/organization & administration , Cooperative Behavior , Health Personnel/statistics & numerical data , Pharmacists/organization & administration , Ambulatory Care Facilities/organization & administration , Ambulatory Care Facilities/statistics & numerical data , Attitude of Health Personnel , Health Personnel/organization & administration , Humans , Interdisciplinary Communication , Interprofessional Relations , Japan , Surveys and Questionnaires
7.
Free Radic Res ; 48(11): 1371-85, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25156503

ABSTRACT

In this study, we show that exposure of human lung cancer A549 cells to cisplatin (cis-diamminedichloroplatinum, CDDP) promotes production of nitric oxide (NO) through generation of reactive oxygen species (ROS) and resulting upregulation of inducible NO synthase (iNOS). The incubation of the cells with a NO donor, diethylenetriamine NONOate, not only reduced the CDDP-induced cell death and apoptotic alterations (induction of CCAAT-enhancer-binding protein homologous protein and caspase-3 activation), but also elevated proteolytic activity of 26S proteasome, suggesting that the activation of proteasome function contributes to the reduction of CDDP sensitivity by NO. Monitoring expression levels of six aldo-keto reductases (AKRs) (1A1, 1B1, 1B10, 1C1, 1C2, and 1C3) during the treatment with the NO donor and subsequent CDDP sensitivity test using the specific inhibitors also proposed that upregulation of AKR1B10 by NO is a key process for acquiring the CDDP resistance in A549 cells. Treatment with CDDP and NO increased amounts of nitrotyrosine protein adducts, indicative of peroxynitrite formation, and promoted the induction of AKR1B10, inferring a relationship between peroxynitrite formation and the enzyme upregulation in the cells. The treatment with CDDP or a ROS-related lipid aldehyde, 4-hydroxy-2-nonenal, facilitated the iNOS upregulation, which was restored by increasing the AKR1B10 expression. In contrast, the facilitation of NO production by CDDP treatment was hardly observed in AKR1B10-overexpressing A549 cells and established CDDP-resistant cancer cells (A549, LoVo, and PC3). Collectively, these results suggest the NO functions as a key regulator controlling AKR1B10 expression and 26S proteasome function leading to gain of the CDDP resistance.


Subject(s)
Aldehyde Reductase/metabolism , Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Lung Neoplasms/drug therapy , Lung Neoplasms/enzymology , Proteasome Endopeptidase Complex/metabolism , Aldehyde Reductase/genetics , Aldehydes/metabolism , Aldo-Keto Reductases , Apoptosis/drug effects , Blotting, Western , Cell Proliferation/drug effects , Humans , Lung Neoplasms/pathology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Peroxynitrous Acid/metabolism , Proteasome Endopeptidase Complex/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
8.
Eur Surg Res ; 51(3-4): 129-37, 2013.
Article in English | MEDLINE | ID: mdl-24280661

ABSTRACT

BACKGROUND: Portal vein embolization (PVE) is considered to improve the safety of major hepatectomy. Various conditions might affect remnant liver hypertrophy after PVE. The aim of the present study was to clarify the factors that affect remnant liver hypertrophy and to establish a prediction formula for the hypertrophy ratio. METHODS: Fifty-nine patients who underwent preoperative PVE for cholangiocarcinoma (39 patients), metastatic carcinoma (10 patients), hepatocellular carcinoma (8 patients), and other diseases (2 patients) were enrolled in this study. For the prediction of the hypertrophy ratio, a formula with stepwise multiple regression analysis was set up. The following parameters were used: age, gender, future liver remnant ratio to total liver (FLR%), plasma disappearance rate of indocyanine green (ICGK), platelet count, prothrombin activity, serum albumin, serum total bilirubin at the time of PVE and the maximum value before PVE (Max Bil), as well as a history of cholangitis, diabetes mellitus, and chemotherapy. RESULTS: The mean hypertrophy ratio was 28.8%. The 5 parameters detected as predictive factors were age (p = 0.015), FLR% (p < 0.001), ICGK (p = 0.112), Max Bil (p < 0.001), and history of chemotherapy (p = 0.007). The following prediction formula was established: 101.6 - 0.78 × age - 0.88 × FLR% + 128 × ICGK - 1.48 × Max Bil (mg/dl) - 21.2 × chemotherapy. The value obtained using this formula significantly correlated with the actual value (r = 0.72, p < 0.001). A 10-fold cross validation also showed significant correlation (r = 0.62, p < 0.001), and a hypertrophy ratio <20% was predictable with a sensitivity of 100% and a specificity of 90.9%. Moreover, technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy showed a significantly smaller increase in the uptake ratio of the remnant liver in patients with prediction values <20% than in those with values ≥20% (6.8 vs. 20.8%, p = 0.030). CONCLUSIONS: The prediction formula can prognosticate the hypertrophy ratio after PVE, which may provide a new therapeutic strategy for major hepatectomy.


Subject(s)
Embolization, Therapeutic , Hepatectomy/methods , Liver/pathology , Portal Vein , Preoperative Care , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Hypertrophy , Liver/blood supply , Male , Middle Aged , Regression Analysis , Retrospective Studies
9.
Cancer Gene Ther ; 19(2): 118-25, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22076042

ABSTRACT

Carrier cells delivering a conditionally replicating adenovirus (CRAd), which selectively replicates in tumor cells and induces tumor cell lysis, have promising potential for treatment of cancer because CRAd-loaded carrier cells evade inhibition by neutralizing anti-adenovirus (Ad) antibodies and because the carrier cells are locally retained at the injection point after local injection. A previous study by Hamada et al. demonstrated that carrier cells (CRAd-containing cell fragments derived from the carrier cells) are engulfed into the target cells, probably through a pathway independent of the primary receptor for Ad, the coxsackievirus and Ad receptor (CAR) (Mol Ther, 15: 1121-1128; 2007); however, it remains to be elucidated whether carrier cells infected with a conventional CRAd, which is composed of subgroup-C Ad serotype-5 (Ad5), mediate antitumor effects on CAR-negative cells. In order to examine whether carrier cells delivering a conventional CRAd (Carrier-F5) induce lysis of CAR-negative tumor cells, CAR-positive and CAR-negative tumor cells were incubated with Carrier-F5. Carrier-F5 mediated efficient killing of CAR-positive tumor cells; however, CAR-negative tumor cells were almost refractory to Carrier-F5. On the other hand, carrier cells loaded with a fiber-substituted CRAd containing fiber proteins of Ad serotype-35 (Ad35) (CRAd-F35), which binds to human CD46 for infection, showed efficient killing of both CAR-positive and CAR-negative tumor cells. Intra-tumoral injection of carrier cells loaded with CRAd-F35 (Carrier-F35) also resulted in efficient regression of both CAR-positive and CAR-negative tumors. These results demonstrated that the expression levels of receptors for Ad are an important factor for CRAd-loaded carrier cell-mediated cancer therapy, and that Carrier-F35 would have potential as a cancer treatment for not only CAR-positive tumors but also CAR-negative tumors.


Subject(s)
Adenocarcinoma/therapy , Adenocarcinoma/virology , Adenoviridae/physiology , Lung Neoplasms/therapy , Lung Neoplasms/virology , Oncolytic Virotherapy/methods , Receptors, Virus/deficiency , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/virology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma of Lung , Adenoviridae/genetics , Animals , Cell Line, Tumor , Coxsackie and Adenovirus Receptor-Like Membrane Protein , Genetic Vectors , HEK293 Cells , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Membrane Cofactor Protein/biosynthesis , Mice , Mice, Inbred BALB C , Receptors, Virus/biosynthesis , Transduction, Genetic , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Virus Replication , Xenograft Model Antitumor Assays
10.
Rev Sci Instrum ; 81(10): 10E525, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21034053

ABSTRACT

A compact tomography camera system consisting of a photomultiplier tube, a multislit optical system, and a band-pass interference filter has been developed. The viewing area and spatial resolution can be configured by the arrangement of the slit system. The camera system has been specially designed for self-organized compact torus experiments having strong magnetohydrodynamics events with a submicrosecond time-scale. The developed system has been tested on a field-reversed configuration formed by the field-reversed theta-pinch. Performance evaluation of the system has been performed by comparison to the former optical system.

11.
Kyobu Geka ; 62(5): 395-8, 2009 May.
Article in Japanese | MEDLINE | ID: mdl-19425382

ABSTRACT

Here we report a case of a rare thymic tumors histologically diagnosed as lipofibroadenoma. The patient was a 32-year-old male who displayed an anterior mediastinal tumor on a chest computed tomography (CT) scan while being treated for pneumonia. The tumor was localized within the thymus, and the diameter was 3 cm. No significant change was observed in the tumor on a CT scan taken 6 months after the 1st scan. Suspecting a thymoma from the CT and magnetic resonance imaging (MRI) findings, we performed a thymothymectomy via a median sternotomy. The histopathological diagnosis was a lipofibroadenoma of the thymus. The findings resembled fibroadenoma of the breast. Lymphocytes were scarce within the tumor with abundant interstitial stroma, and the tumor epithelial cells displayed restiform and dendritic structures. The epithelial cells were mostly negative for Ki-67 immunohistochemical staining. A very small amount of calcification was detected within the tumor using alizarin red staining. Based on the histopathological findings, it was considered to be a benign tumor with little growth potential, and which had been present for a long period of time.


Subject(s)
Fibroadenoma/pathology , Lipoma/pathology , Thymoma/pathology , Thymus Neoplasms/pathology , Adult , Humans , Male
12.
J Fish Biol ; 74(8): 1756-73, 2009 May.
Article in English | MEDLINE | ID: mdl-20735669

ABSTRACT

Three morphologically and genetically distinct forms of the genus Carassius were collected from the Ob River system, Kazakhstan, Central Asia; Carassius carassius, Carassius gibelio gibelio and an unknown stock tentatively referred to as Carassius gibelio sub-species M. The last mentioned had 33-41 gill rakers, being intermediate between the other two forms (23-27 in C. carassius and 44-49 in C. g. gibelio), and five scales in the upper transverse series, less than in the others. It also had a relatively larger erythrocyte suggesting triploidy and an mtDNA haplotype distinct from all other known crucian carps. Comparative mtDNA phylogenetic analysis suggested that C. gibelio gibelio in the Ob River system was introduced from China and the Amur River, the same possibly being true for European C. gibelio gibelio based on published haplotypes. C. gibelio sub-species M is thought to be more widely distributed in central Asia, probably extending as far west as European Russia.


Subject(s)
Carps/anatomy & histology , Carps/genetics , DNA, Mitochondrial/genetics , Phylogeny , Animals , Carps/classification , Erythrocytes/cytology , Female , Genetic Variation , Haplotypes , Kazakhstan , Male , Sequence Analysis, DNA
13.
Kyobu Geka ; 61(2): 164-7, 2008 Feb.
Article in Japanese | MEDLINE | ID: mdl-18268958

ABSTRACT

23 year-old non-smoking male who had underwent bilateral video-assisted thoracoscopic surgery (VATS) bullectomy for spontaneous pneumothorax using surgical stapler (Endo GIA, Tyco Healthcare) 5 years before, referred to our hospital due to hemoptysis. Chest computed tomography (CT) revealed infiltrative shadow surrounding stapled-line at right pulmonary apex. Aspiration-shadows were scattered in right lung parenchyma. Bronchoscopy revealed bloody clot extended from right B1 to main bronchi. These findings suggested that the cause of bloody sputum was bleeding from the tissue around staples used in VATS bullectomy. On admission he treated with hemostatic agents, and bloody sputum and abnormal CT shadows disappeared. Metallic surgical staplers may cause airway bleeding after surgery in its chronic stage, although complications due to them are rare.


Subject(s)
Hemoptysis/etiology , Sputum , Sutures/adverse effects , Adult , Hemoptysis/diagnostic imaging , Hemoptysis/therapy , Humans , Male , Pneumonectomy , Pneumothorax/surgery , Postoperative Complications/etiology , Thoracic Surgery, Video-Assisted , Time Factors , Tomography, X-Ray Computed
14.
Apoptosis ; 7(6): 519-25, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12370494

ABSTRACT

Intracellular acidification is known to be involved in the initiation phase of apoptosis. However, the necessity of intracellular acidic conditions in the execution phase of apoptosis remains unknown. In this study, we found that in HL-60 cells imidazole induces cell death, associated with intracellular acidification, caspase-3 activation and DFF-45 cleavage, but not oligonucleosomal DNA fragmentation. A caspase inhibitor prevented cell death but not intracellular acidification. When pHi was neutralized by changing from imidazole-containing medium to fresh medium, oligonucleosomal DNA fragmentation and increased caspase-3 activity was observed in the imidazole-treated HL-60 cells. Furthermore, the DNA fragmentation induced by intracellular neutralization was inhibited by caspase inhibitor treatment. These results indicate that imidazole induces caspase-dependent cell death, and suggest that maintaining pHi in the neutral range is essential for the induction of oligonucleosomal DNA fragmentation in the execution phase of apoptosis.


Subject(s)
Apoptosis/drug effects , Apoptosis/physiology , Imidazoles/pharmacology , Apoptosis Regulatory Proteins , Caspase 3 , Caspases/metabolism , DNA Fragmentation/drug effects , Enzyme Activation/drug effects , HL-60 Cells , Humans , Hydrogen-Ion Concentration , Intracellular Fluid/metabolism , Proteins/metabolism
15.
Vet Res Commun ; 26(3): 171-7, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12090289

ABSTRACT

The concentrations of C-reactive proteins (CRP) in the plasma of five beagle dogs experimentally inoculated with Ehrlichia canis increased markedly. The concentrations began to increase between 4 and 16 days and peaked between 15 and 42 days after inoculation of E. canis. The peak concentrations ranged from 217.8 to 788.8 microg/ml (452.6 +/- 228.1 SD). After the peak, the concentrations of CRP decreased rapidly. The PCR product of 16S rRNA of E. canis became detectable in the five dogs between 18 and 27 days after inoculation of E canis. Antibodies to E canis were detected in plasma from the dogs between 5 and 15 days after inoculation of E. canis. The timings of seroconversion and of the start of the increase in CRP were approximately similar and the high concentrations of CRP in the plasma of the dogs tended to become apparent when the PCR product of 16 S rRNA of E. canis became detectable.


Subject(s)
C-Reactive Protein/biosynthesis , Dog Diseases/blood , Ehrlichia canis/growth & development , Ehrlichiosis/veterinary , Animals , Antibodies, Bacterial/blood , C-Reactive Protein/analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Dog Diseases/microbiology , Dogs , Ehrlichia canis/genetics , Ehrlichiosis/blood , Ehrlichiosis/microbiology , Fluorescent Antibody Technique, Indirect/veterinary , Polymerase Chain Reaction , RNA, Ribosomal, 16S/chemistry , RNA, Ribosomal, 16S/genetics
16.
Am J Respir Crit Care Med ; 164(10 Pt 1): 1879-84, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11734440

ABSTRACT

Nitric oxide (NO) produced in the airways can be either detrimental or protective to the host. To investigate the role of NO in the pathogenesis of exercise-induced bronchoconstriction (EIB), we measured exhaled NO (ENO) after exercise challenge in 39 asthmatic and six normal children. FEV(1) and ENO were measured before and at 0, 5, 10, and 15 min after exercise performed on a treadmill for 6 min. EIB was defined as a decrease in FEV(1) of more than 15% after the exercise. Normal children (control group) did not have EIB. Twenty-one patients with asthma had EIB (EIB group) whereas the remaining 18 patients did not (non-EIB group). The baseline ENO value was significantly higher in the asthmatic children than in the normal children, and there was a positive correlation between the maximal percent decrease in FEV(1) and the baseline ENO value (r = 0.501, p = 0.012). At the end of the exercise, ENO had decreased in all the subjects. In the non-EIB and control groups, ENO rebounded to above the baseline at 5 min after the exercise and thereafter. In contrast, ENO remained at a decreased level in the EIB group. The change in ENO did not correlate with the change in minute ventilation, and beta-agonist inhalation at the peak of EIB that accelerated the recovery of FEV(1) did not affect the depressed level of ENO, demonstrating that the reduction of ENO is not a simple consequence of increased ventilation nor airway obstruction. Among the EIB group, steroid-treated patients showed sooner recovery in ENO after the exercise than steroid-naive patients. Our study suggests that NO production in response to exercise may be impaired in patients with EIB, and that ENO represents not only airway inflammation but also a protective function of NO in EIB.


Subject(s)
Asthma, Exercise-Induced/metabolism , Breath Tests , Nitric Oxide/analysis , Nitric Oxide/physiology , Administration, Inhalation , Adolescent , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Agonists/therapeutic use , Analysis of Variance , Anti-Inflammatory Agents/therapeutic use , Asthma, Exercise-Induced/diagnosis , Asthma, Exercise-Induced/drug therapy , Asthma, Exercise-Induced/physiopathology , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Case-Control Studies , Child , Drug Therapy, Combination , Exercise Test , Female , Forced Expiratory Volume/drug effects , Heart Rate/drug effects , Humans , Male , Procaterol/pharmacology , Procaterol/therapeutic use , Steroids , Time Factors
17.
J Nat Prod ; 64(11): 1421-5, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11720524

ABSTRACT

Five new halogenated prostanoids 1-4 and 6 were isolated from the Okinawan soft coral Clavularia viridis. The gross structure of 1 was elucidated mainly on the basis of NMR spectral data. The relative and absolute configurations were determined by analysis of NOESY and CD data, chemical conversion, and the modified Mosher's method. The structures of 2-4 and 6 were deduced by comparison of their spectral data with those of 1. Compound 1 demonstrated cytotoxic activity.


Subject(s)
Cnidaria/chemistry , Hydrocarbons, Halogenated/isolation & purification , Prostaglandins/isolation & purification , Algorithms , Animals , Cells, Cultured/drug effects , Circular Dichroism , Colorectal Neoplasms , Drug Screening Assays, Antitumor , Fibroblasts/drug effects , Humans , Hydrocarbons, Halogenated/chemistry , Hydrocarbons, Halogenated/pharmacology , Japan , Leukemia, Lymphoid , Lung/cytology , Lung/drug effects , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Prostaglandins/chemistry , Prostaglandins/pharmacology , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Stereoisomerism , Tumor Cells, Cultured/drug effects
18.
Biochem Biophys Res Commun ; 287(3): 714-20, 2001 Sep 28.
Article in English | MEDLINE | ID: mdl-11563854

ABSTRACT

Glycation of plasma proteins may contribute to an excess risk of developing atherosclerosis in patients with diabetes mellitus. Although it is believed that high-density lipoprotein (HDL) is nonenzymatically glycosylated at an increased level in diabetic individuals, little is known about a possible linkage between glycated HDL and endothelium dysfunction in diabetes. This study set out to clarify whether glucose-modified HDL affects the function of endothelial cells by examining the apoptosis of cultured human aortic endothelial cells (HAECs) exposed to a glycated-oxidized HDL (gly-ox-HDL) prepared in vitro. Incubation of HAECs with 100 microg/ml of gly-ox-HDL for 48 h showed apoptotic features, such as cell shrinkage, membrane blebbing, and concentration and fragmentation of the nucleus, and the degree of apoptosis was dose-dependent on the glucose used in the preparation of gly-ox-HDL. Stimulation of HAECs with gly-ox-HDL elicited a marked increase in caspase 3 activity and the expressions of active caspase 3 and caspase 9, whereas concomitant treatment with a caspase 3 inhibitor significantly blocked gly-ox-HDL-induced apoptosis of HAECs. The release of cytochrome c into cytosols markedly increased in HAECs during the treatment with gly-ox-HDL. The increased expressions of Bax and Bad were detected in HAECs incubated for 24 h with gly-ox-HDL, but gly-ox-HDL failed to interfere with the expression of Bcl-2 and Bcl-x. Moreover, in vitro experiments with HDL (gly-HDL) glycated in the presence of 2 mM EDTA and Cu(2+)-oxidized HDL suggested that the apoptotic effect of gly-ox-HDL on endothelial cells might be due to an additional oxidative modification of gly-HDL. Taken altogether, additional oxidation of HDL under hyperglycemic conditions may induce endothelial apoptosis through a mitochondrial dysfunction, following the deterioration of vascular function.


Subject(s)
Apoptosis , Endothelium, Vascular/pathology , Lipoproteins, HDL/metabolism , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2 , Aorta/cytology , Blotting, Western , Carrier Proteins/biosynthesis , Caspase 3 , Caspase 9 , Caspases/metabolism , Cell Nucleus/metabolism , Cells, Cultured , Cytochrome c Group/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Glucose/pharmacology , Humans , Lipoproteins, HDL/pharmacology , Microscopy, Phase-Contrast , Protein Binding , Proto-Oncogene Proteins/biosynthesis , Time Factors , bcl-2-Associated X Protein , bcl-Associated Death Protein
19.
Apoptosis ; 6(4): 263-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11445668

ABSTRACT

Phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane in apoptotic cell death. However, the roles of PS in apoptotic signaling are still unclear. In this study, we found that exogenous PS, but not other phospholipids, induced cell death in adherent cells, but not in suspension culture. The cell death exhibited typical features of apoptosis such as cell shrinkage, nuclear fragmentation and abnormal chromatin condensation. When PS was added to CHO-K1 cells in monolayer culture, they began to show changes in cell shape and actin cytoskeleton and protein kinase C (PKC) activity, followed by cell detachment, caspase activation, cleavage of focal adhesion kinase (FAK) and finally loss of viability. These results suggested that PS causes apoptosis through actin disorganization, cell detachment and cleavage of FAK.


Subject(s)
Apoptosis , Cell Adhesion , Phosphatidylserines/physiology , Actins/physiology , Animals , CHO Cells , Cell Division , Cell Survival , Cricetinae , HL-60 Cells , Humans , Phosphatidylserines/pharmacology , Tumor Cells, Cultured
20.
Prostate ; 47(1): 59-65, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11304730

ABSTRACT

BACKGROUND: Prostatic tumors are well known to progress to hormonal therapy-resistant terminal states. At this stage, there are no chemotherapeutic agents to affect clinical outcome. An effective cell death inducer for these prostate cells may be a candidate as an attractive antitumor agent. The extracts from S. repens have been used to improve the state of prostatic diseases and we have attempted to identify the effective component from the extract. METHODS: Cell viability was examined in LNCaP cells, an in vitro model for hormonal therapy-resistant prostatic tumor. RESULTS: We found that exposure of the extract from S. repens resulted in cell death of LNCaP cells. We also identified myristoleic acid as one of the cytotoxic components in the extract. The cell death exhibited both apoptotic and necrotic nuclear morphology as determined by Hoechst 33342 staining. Cell death was also partially associated with caspase activation. CONCLUSIONS: It was demonstrated that the extract from S. repens and myristoleic acid induces mixed cell death of apoptosis and necrosis in LNCaP cells. These results suggest that the extract and myristoleic acid may develop attractive new tools for the treatment of prostate cancer.


Subject(s)
Androgen Antagonists/toxicity , Apoptosis/drug effects , Fatty Acids, Monounsaturated/toxicity , Plant Extracts/toxicity , Prostatic Neoplasms , Amino Acid Chloromethyl Ketones/pharmacology , Caspase 3 , Caspase Inhibitors , Caspases/metabolism , Enzyme Inhibitors/pharmacology , Humans , Male , Necrosis , Serenoa , Tumor Cells, Cultured/enzymology , Tumor Cells, Cultured/pathology
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