Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 74
Filter
2.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 690-695, 2021 Jul 20.
Article in Chinese | MEDLINE | ID: mdl-34371541

ABSTRACT

Objective: To investigate the safety and efficacy of ultrasound-guided percutaneous radiofrequency ablation (RFA) for caudate lobe hepatocellular carcinoma (HCC) and the failure factors of incomplete tumor ablation. Methods: Twenty-four cases with caudate lobe hepatocellular carcinoma who underwent ultrasound-guided percutaneous RFA in the Affiliated Tumor Hospital of Zhengzhou University from January 2017 to October 2019 were enrolled. The ablation effect and complications conditions were recorded, and the primary technical effectiveness and local tumor progression (LTP) were evaluated. Results: Among 24 cases, 20 cases had complete ablation at one session, 4 cases had incomplete ablation, and after supplementary radiofrequency ablation all cases had achieved complete ablation. There was no evidence of local tumor progression in 24 cases after one-month postoperative evaluation. The primary technical effectiveness rate was 100%. The postoperative follow-up was 2 to 29 months (median follow-up time was 18 months). Of the 24 cases after ablation, LTP were detected in 11 cases, of which only 3 cases had distant intrahepatic recurrence, 1 case had distant intrahepatic recurrence and distant metastasis, and 5 cases had only distant metastasis, 2 cases died, and 4 cases had SIR grade B complications related to ablation. Conclusion: Ultrasound-guided percutaneous radiofrequency ablation was safe and effective for caudate lobe hepatocellular carcinoma. In addition, the distance between the tumor and the inferior vena cava < 0.5cm is a suspected risk factor for incomplete ablation of caudate lobe hepatocellular carcinoma (P < 0.05).


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Radiofrequency Ablation , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Neoplasm Recurrence, Local , Retrospective Studies , Treatment Outcome , Ultrasonography, Interventional
3.
Zhonghua Wai Ke Za Zhi ; 58(10): 770-775, 2020 Oct 01.
Article in Chinese | MEDLINE | ID: mdl-32993264

ABSTRACT

Objective: To examine the safety and effectiveness of ultrasound-guided percutaneous radiofrequency ablation in the treatment of liver malignant tumor under subcardiac. Methods: The clinical data of 26 patients (31 tumors) with subcardiac liver malignant tumors who underwent ultrasound-guided percutaneous radiofrequency ablation from January 2017 to October 2019 at the Affiliated Tumor Hospital of Zhengzhou University were retrospectively analyzed. There were 21 males and 5 females. The age was 55 years old (range: 40 to 77 years old) .There were 14 cases of primary liver cancer and 12 cases of metastatic liver cancer. The maximum diameter of tumor was (2.3±1.0) cm (range: 1.0 to 4.2 cm) .According to the maximum diameter of the tumor, 1∶1 match was made between 27 non-subcardiac patients admitted at the same time and a total of 36 liver malignant tumors. subcardiac tumor is defined as tumor ≤1 cm from pericardium in sagittal or coronal imaging. The ablation effect and complications were recorded, and the one-time complete ablation rate, main technical efficiency and complications were evaluated. The preoperative baseline characteristics, ablation effect and complications of the two groups of patients were collected and counted. Single factor analysis and Logistic regression analysis were used to analyze the independent risk factors that affect the ablation effect of ultrasound-guided percutaneous radiofrequency ablation for liver malignant tumors under subcardiac. Results: The one-time complete ablation rate of tumor after radiofrequency ablation was 80.8% (21/26) in the subcardiac group and 92.6% (25/27) in the non-subcardiac group. There was no significant difference between the two groups (P>0.05) . No evidence of local tumor progression was found in the follow-up evaluation of the two groups one month after radiofrequency ablation, and the main technical effective rate was 100%.Ablation-related complications occurred in 2 patients in the subcardiac group. Multivariate analysis both showed that the distance between tumor margin and pericardium ≤5 mm was an independent risk factor affecting radiofrequency ablation (OR=0.020, 95%CI: 0.001 to 0.454, P=0.014) . Conclusions: Ultrasound-guided percutaneous radiofrequency ablation can safely and effectively treat liver malignant tumor under subcardiac. When there is a tumor near the patient's heart (the distance between the edge of the tumor and pericardium is ≤5 mm) , special attention should be paid to formulate a detailed and reasonable ablation plan to minimize tumor residue.


Subject(s)
Liver Neoplasms , Radiofrequency Ablation , Adult , Aged , Female , Humans , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Male , Middle Aged , Radiofrequency Ablation/methods , Retrospective Studies , Treatment Outcome , Ultrasonography, Interventional
5.
Radiat Res ; 184(1): 56-65, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26121228

ABSTRACT

Previously reported studies of the Techa River Cohort have established associations between radiation dose and the occurrence of solid cancers and leukemia (non-CLL) that appear to be linear in dose response. These analyses include 17,435 cohort members alive and not known to have had cancer prior to January 1, 1956 who lived in areas near the river or Chelyabinsk City at some time between 1956 and the end of 2007, utilized individualized dose estimates computed using the Techa River Dosimetry System 2009 and included five more years of follow-up. The median and mean dose estimates based on these doses are consistently higher than those based on earlier Techa River Dosimetry System 2000 dose estimates. This article includes new site-specific cancer risk estimates and risk estimates adjusted for available information on smoking. There is a statistically significant (P = 0.02) linear trend in the smoking-adjusted all-solid cancer incidence risks with an excess relative risk (ERR) after exposure to 100 mGy of 0.077 with a 95% confidence interval of 0.013-0.15. Examination of site-specific risks revealed statistically significant radiation dose effects only for cancers of the esophagus and uterus with an ERR per 100 mGy estimates in excess of 0.10. Esophageal cancer risk estimates were modified by ethnicity and sex, but not smoking. While the solid cancer rates are attenuated when esophageal cancer is removed (ERR = 0.063 per 100 mGy), a dose-response relationship is present and it remains likely that radiation exposure has increased the risks for most solid cancers in the cohort despite the lack of power to detect statistically significant risks for specific sites.


Subject(s)
Neoplasms/epidemiology , Adult , Aged , Cohort Studies , Dose-Response Relationship, Radiation , Female , Humans , Incidence , Male , Middle Aged , Rivers , Russia/epidemiology , Time Factors
6.
Lupus ; 22(11): 1135-41, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23995863

ABSTRACT

OBJECTIVE: The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy. METHODS: Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥ 2 immunosuppressive regimens. While prednisolone (≤ 10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months. RESULTS: Twenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V+III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal. CONCLUSIONS: Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.


Subject(s)
Immunosuppressive Agents/administration & dosage , Lupus Nephritis/drug therapy , Mycophenolic Acid/analogs & derivatives , Tacrolimus/administration & dosage , Adult , Creatinine/urine , Drug Therapy, Combination , Female , Humans , Lupus Nephritis/immunology , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Prospective Studies , Serum Albumin/analysis , T-Lymphocytes/immunology , Tacrolimus/adverse effects
7.
Eur Rev Med Pharmacol Sci ; 17(3): 349-55, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23426538

ABSTRACT

BACKGROUND: Severe acute pancreatitis (SAP) is a serious systemic disease with a sustained high mortality rate. Extensive evidence has shown that gut barrier dysfunction plays a critical role in the pathophysiology of SAP. AIM: Investigating the role of intestinal mucosa oxidative stress in gut barrier dysfunction of SAP. MATERIALS AND METHODS: Twenty-four BALB/c mice were randomly divided into two groups with twelve mice each group. The SAP group mice received six intraperitoneal injections of cerulein (50 µg/kg) at 1-hour intervals, then given one intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS from E. coli) for inducing SAP. Normal saline was given to the mice of control group. The animals of each group were averaged to two batches. Four and eight hours after the final injection, respectively, mice were anesthetized and blood and tissue samples were harvested for examination. The pathological changes of pancreas and gut were observed and scored. The serum levels of diamine oxidase (DAO), amylase and tumor necrosis factor-alpha (TNF-α) were measured. The contents of malondialdehyde (MDA) and reduced glutathione (GSH) and activity of superoxide dismutase (SOD) and xanthine oxidase (XO) in gut mucosa were detected. In gut mucosa, the caspase-3 activity was measured and the cell apoptosis and apoptosis index (AI) were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The data were analyzed by ANOVA and t-test. RESULTS: At four and eight hours after SAP induction, the SAP group mice had significantly higher pancreatic and gut pathological scores (p < 0.01) and increased serum levels of amylase (p < 0.05), DAO and TNF-α (p < 0.01) and increased MDA contents and XO activity of gut mucosa (p < 0.01) compared with those of control mice. There were significantly lower GSH contents (p < 0.05) and SOD activity (p < 0.01) of gut mucosa in the SAP mice. It was also observed that the gut mucosa cells of SAP mice had significantly higher caspase-3 activity and apoptosis index (p < 0.01). CONCLUSIONS: In SAP, waterfall-style release of inflammatory factors such as TNF-α led to ischemia-reperfusion injury of gut mucosa which resulted in serious oxidative stress and activation of caspase-3 pathway and severe apoptosis of gut mucosa. Therefore, intestinal mucosal oxidative stress may play an important role in the mechanism of gut barrier dysfunction.


Subject(s)
Intestinal Mucosa/physiopathology , Oxidative Stress , Pancreatitis/physiopathology , Reperfusion Injury/physiopathology , Acute Disease , Analysis of Variance , Animals , Apoptosis , Caspase 3/metabolism , Ceruletide/toxicity , Disease Models, Animal , In Situ Nick-End Labeling , Inflammation Mediators/metabolism , Male , Mice , Mice, Inbred BALB C , Random Allocation , Severity of Illness Index , Tumor Necrosis Factor-alpha/metabolism
8.
Int J Immunopathol Pharmacol ; 25(1): 219-30, 2012.
Article in English | MEDLINE | ID: mdl-22507334

ABSTRACT

Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-beta, pIkB/IkB, NFkB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Heptanoic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Neuralgia/drug therapy , Neuroprotective Agents/pharmacology , Pyrroles/pharmacology , Animals , Atorvastatin , Disease Models, Animal , Hyperalgesia/drug therapy , Immunohistochemistry , Male , NF-kappa B/analysis , Nitric Oxide Synthase Type II/analysis , Nitric Oxide Synthase Type III/analysis , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/analysis
9.
Neuroscience ; 164(4): 1477-83, 2009 Dec 29.
Article in English | MEDLINE | ID: mdl-19778584

ABSTRACT

Locomotion is a complex behavior affected by many different brain- and spinal cord systems, as well as by variations in the peripheral nervous system. Recently, we found increased gene expression for EphA4, a gene intricately involved in motor neuron development, between high-active parental strain C57BL/6J and the low-active chromosome substitution strain 1 (CSS1). CSS1 mice carry chromosome 1 from A/J mice in a C57BL/6J genetic background, allowing localization of quantitative trait loci (QTL) on chromosome 1. To find out whether differences in motor neuron anatomy, possibly related to the changes in EphA4 expression, are involved in the motor activity differences observed in these strains, motor performance in various behavioral paradigms and anatomical differences in the ventral roots were investigated. To correlate the behavioral profiles to the spinal motor neuron morphology, not only CSS1 and its parental strains C57BL/6J (host) and A/J (donor) were examined, but also a set of other mouse inbred strains (AKR/J, 129x1/SvJ and DBA/2J). Significant differences were found between inbred strains on home cage motor activity levels, the beam balance test, grip test performance, and on alternating versus synchronous hind limb movement (hind limb hopping). Also, considerable differences were found in spinal motor neuron morphology, with A/J and CSS1 showing smaller, possibly less developed, motor neuron axons compared to all other inbred strains. For CSS1 and C57BL/6J, only genetically different for chromosome 1, a correlation was found between motor activity levels, synchronous hind limb movement and neuro-anatomical differences in spinal motor neurons. Inclusion of the other inbred strains, however, did not show this direct correlation. These data verifies the complex nature of the mammalian motor system that may be further dissected using genetic mapping populations derived from these inbred strains.


Subject(s)
Axons/ultrastructure , Motor Activity/physiology , Spinal Nerve Roots/ultrastructure , Animals , Male , Mice , Mice, Inbred Strains , Motor Activity/genetics , Motor Neurons/ultrastructure , Species Specificity
10.
Scand J Rheumatol ; 38(2): 121-7, 2009.
Article in English | MEDLINE | ID: mdl-18991189

ABSTRACT

OBJECTIVES: To examine the effect of disease activity and damage on health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients and matched controls were recruited for a study of HRQoL using the Medical Outcomes Study Short Form-36 (SF-36). SLE activity and damage was assessed by the Safety of Oestrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) and the American College of Rheumatology/Systemic Lupus International Collaborating Clinics (ACR/SLICC) Damage Index (SDI), respectively. Patients were prospectively followed for repeat HRQoL assessment at 2 years. The effects of cumulative disease activity and new damage on changes in SF-36 scores were evaluated. RESULTS: One hundred and fifty-five patients were studied (94% women; age 37.8+/-11.3 years; SLE duration 7.2+/-5.4 years). Fifty (32%) patients had active disease and 75 (48%) had organ damage at baseline. Compared with age- and gender-matched controls, SLE patients had lower SF-36 scores, and the difference remained significant after adjustment for income and education level. SF-36 scores in SLE patients correlated inversely with SDI but not with SELENA-SLEDAI scores. After 2 years, there was a significant drop in the mental component score of the SF-36. Regression analysis revealed that new damage was the only determinant for a reduction in SF-36 scores. Patients with higher cumulative disease activity had a greater drop in bodily pain and general health subscores. CONCLUSIONS: Impaired HRQoL is more common in SLE patients than controls, regardless of age, sex, education and poverty. Pre-existing organ damage is associated with poorer HRQoL and new damage predicts a further decline in HRQoL. Persistent disease activity is associated with deterioration in certain domains of the SF-36.


Subject(s)
Health Status , Lupus Erythematosus, Systemic/physiopathology , Quality of Life , Sickness Impact Profile , Adult , Female , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/pathology , Male , Prospective Studies , Severity of Illness Index
11.
Lupus ; 17(12): 1103-7, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19029278

ABSTRACT

The aim of this study is to determine the risk and predictive factors for work disability in patients with SLE. A cross-sectional questionnaire study was performed to evaluate the employment status of a sample of consecutive Chinese patients with SLE. Demographic, socioeconomic data (age, gender, marital status, years of education and household income), employment status, self-reported fatigue score and disease characteristics (SLE duration, organ damage and disease activity) were collected. Work disability was defined by the failure to work due to SLE. The cumulative incidence of work disability since the time of SLE diagnosis was studied by a Kaplan Meier's plot, and factors predictive of work disability were studied by Cox regression. A total of 147 patients with SLE were studied (mean age = 39.4 +/- 11.3 years; 95% women). Among 105 patients who were working at the time of SLE diagnosis, 39 (37%) lost their ability to work as a result of SLE after a mean disease duration of 10.0 +/- 6.1 years. Twenty-two (56%) patients lost their work ability within 2 years of diagnosis of SLE. The self-reported reasons for job loss were musculoskeletal pain (87%), skin disease (26%), renal problem (21%), fatigue (85%), memory deterioration (51%), anxiety or depressive symptoms (74%), too frequent sick leave (10%) and long-term hospitalisation (10%). The cumulative risk of work disability was 36% at 5 years after SLE diagnosis. In a Cox regression model, age (HR = 1.06 [1.02-1.11] per year; P = 0.008), self-reported fatigue score (HR = 1.06 [1.01-1.10] per point; P = 0.01) and mean disease activity score in the preceding two years (HR = 1.20 [1.02-1.42] per point; P = 0.03) were independently associated with working disability. In all, 37% of this group of patients with SLE lost their work ability after having the disease for 10 years. More than 50% of these patients developed work disability within the first 2 years of SLE diagnosis. Older age, fatigue and more active disease were independent predictors of work disability.


Subject(s)
Asian People/statistics & numerical data , Disability Evaluation , Employment/statistics & numerical data , Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/physiopathology , Unemployment/statistics & numerical data , Adult , Female , Hong Kong/epidemiology , Humans , Incidence , Male , Middle Aged , Morbidity , Predictive Value of Tests , Prevalence , Regression Analysis , Risk Factors , Surveys and Questionnaires
12.
J Ethnopharmacol ; 101(1-3): 68-74, 2005 Oct 03.
Article in English | MEDLINE | ID: mdl-15878812

ABSTRACT

In this study, the potential anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on LPS-induced lung injury were investigated and compared to the profile of dexamethasone (DEXA) in a pre-clinical animal model. Post-treatment with SHXT (75 mg/kg), baicalin (1.5 mg/kg) and DEXA (0.5 mg/kg), significantly inhibited LPS-induced hypotension, lung edema and acute survival rates. Western blotting analysis results indicated that all of them significantly inhibited LPS-induced iNOS, TGF-beta, p38MAPK, and ICAM-1 expressions in the lung tissues. Results from ELISA analysis showed that SHXT, baicalin and DEXA all decreased plasma levels of IL-1beta, TNF-alpha, and MCP-1 caused by LPS. Based on these findings, SHXT and baicalin decreased plasma concentrations of IL-1beta, TNF-alpha, MCP-1, and expressions of TGF-beta, ICAM-1, phosphorylated p38 MAPK, and iNOS, which were associated with lung injury and lethality. These evidences indicated that SHXT and baicalin showed strong anti-inflammatory activity, similar to that observed for DEXA, and therefore implicated that herbal SHXT might be therapeutically useful for the treatment of endotoxic lung injury.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Lung/drug effects , Animals , Blood Pressure/drug effects , Lipopolysaccharides , Male , Nitric Oxide Synthase Type II/metabolism , Phosphorylation , Pulmonary Edema/drug therapy , Rats , Rats, Wistar , Transforming Growth Factor beta/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , p38 Mitogen-Activated Protein Kinases/metabolism
13.
Int J Oncol ; 19(6): 1193-201, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11713589

ABSTRACT

Hypothalamic gonadotropin-releasing hormone (GnRH) plays a central role in the regulation of the mammalian reproductive systems as a releasing hormone of pituitary gonadotropins. However, a number of studies have shown that GnRH or its receptor are also expressed in some reproductive organs including prostate gland, mammary gland, ovary and placenta, tumors and tumor cell lines derived from these organs, suggesting that this peptide hormone may have other extrapituitary functions in addition to its role as a gonadotropin-releasing hormone. Moreover, it has been demonstrated that GnRH analogs exert some direct inhibitory effects on the proliferation of human and rat prostate cancer cells, probably mediated by its own specific receptors expressed in these tumor cells. In the present study, we investigated the mRNA expression of GnRH and its receptor in normal Noble rat prostate gland, and in three rat models of prostate cancer including the sex hormone-induced Noble rat model, an androgen-independent Noble rat prostatic tumor (AIT) and Dunning rat prostatic adenocarcinomas by RT-PCR and Southern blot analyses. The results showed that GnRH mRNA was expressed in the normal, hormone-treated and neoplastic rat prostates, in addition to its positive control expression in the hypothalamus, whereas its receptor was only detected in the androgen-dependent Dunning R3327H tumor. The detection of both GnRH and its receptor in the androgen-dependent Dunning R3327H tumor tissue suggests that this peptide hormone may have some autocrine and paracrine regulatory functions in this tumor. However, the gene expression of GnRH receptor was not detected in two androgen-independent Dunning tumor sublines and the Noble rat prostatic tumor, AIT, suggesting that the expression of GnRH receptor is lost or down-regulated in the prostatic tumors during the progression to a hormone-independent phenotype.


Subject(s)
Adenocarcinoma/metabolism , Gonadotropin-Releasing Hormone/genetics , Prostate/metabolism , Prostatic Neoplasms/metabolism , RNA, Messenger/metabolism , RNA, Neoplasm/metabolism , Receptors, LHRH/genetics , Androgens/metabolism , Animals , Blotting, Southern , DNA Primers/chemistry , Disease Models, Animal , Gonadotropin-Releasing Hormone/metabolism , Male , Polymerase Chain Reaction , RNA, Neoplasm/genetics , Rats , Receptors, LHRH/metabolism , Reverse Transcriptase Polymerase Chain Reaction
14.
Bioorg Med Chem Lett ; 11(17): 2393-6, 2001 Sep 03.
Article in English | MEDLINE | ID: mdl-11527739

ABSTRACT

Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Influenza A virus/drug effects , Thioamides/chemistry , Thioamides/pharmacology , Amines/chemistry , Cells, Cultured/virology , Drug Evaluation, Preclinical , Hemolysis/drug effects , Humans , Influenza A virus/pathogenicity , Magnetic Resonance Spectroscopy , Membrane Fusion/drug effects , Molecular Structure , Quinolizines/chemistry , Quinolizines/pharmacology , Stereoisomerism , Structure-Activity Relationship
15.
J Synchrotron Radiat ; 8(Pt 2): 496-8, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11512828

ABSTRACT

In this study, five epitaxial [Co(t nm)/Pt(1 nm)]30, multilayer samples (t=0.16-1.07 nm) were studied using polarized X-ray absorption spectroscopy method. These samples were prepared on Mo(110)/ Al2O3(11-20) substrates by MBE technique. The results show that the Co layer is more like an fcc pseudomorphic structure for the Co thickness of less than 0.3 nm. For Co layer thickness of 1 nm, the first shell distance is 0.25 nm, which is very close to the Co-Co distance of bulk hcp Co. On the other hand, for Co layer of less than 0.3 nm, the in plane first shell distance is expanded by 4% and most of the neighboring atoms are Pt atoms. The fitting results of the Co/Pt multilayers seem to support a sharp boundary model rather than an interdiffusion model.

16.
Kaohsiung J Med Sci ; 17(1): 16-24, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11411255

ABSTRACT

Bone morphogenetic proteins (BMPs) have been shown to play an important role in cell growth and differentiation. BMPs, a rapidly expanding family closely related to transforming growth factor-beta (TGF-beta) superfamily, have been proven recently to possess a regulatory role and neurotrophic capacity in neurogenesis. The aim of the present study is to reveal the relationship among BMPs, peripheral nerve and neoplastic lesions of nerve sheath tumors. The mRNA transcriptions of BMP 2, 3, 4 and 5 in 12 cases of schwannoma, four cases of malignant schwannoma and three cases of trigeminal neuralgia were detected using an in situ hybridization technique. Our results demonstrated that the myelin sheaths of schwann cell from the peripheral neuroectomy of trigeminal neuralgia were positively expressing mRNA of BMP-2, 3, 4 and 5. However, the nerve fibers of trigeminal nerve showed only BMP-2 positive staining. All of the neoplastic lesions of nerve sheath showed a consistent but variant expression of BMP-2, 3, 4, and 5. Except for the BMP-4 mRNA, the expression signals of BMP-2, 3 and 5 mRNA in malignant schwannoma were relatively lower than in benign lesions. On the basis of the findings, we concluded that selected members of BMPs existed in the peripheral nerves and might contribute to the health maintenance, proliferation, regeneration and neoplastic transformation of the peripheral nerve system. Moreover, the effects of BMP-2, 3, 4 and 5 on peripheral nerve system and its neoplastic transformation might be widespread, diverse and antagonistic.


Subject(s)
Bone Morphogenetic Proteins/genetics , Nerve Sheath Neoplasms/metabolism , RNA, Messenger/analysis , Transforming Growth Factor beta , Adult , Bone Morphogenetic Protein 2 , Bone Morphogenetic Protein 3 , Bone Morphogenetic Protein 4 , Bone Morphogenetic Protein 5 , Humans , In Situ Hybridization , Middle Aged
17.
J Cell Biochem ; 80(3): 304-12, 2001.
Article in English | MEDLINE | ID: mdl-11135359

ABSTRACT

Gonadotropin-releasing hormone (GnRH), acting via the GnRH receptor, elicited rapid extracellular acidification responses in mouse gonadotrope-derived alphaT3-1 cells as measured by the Cytosensor microphysiometer, which indirectly monitors cellular metabolic rates. GnRH increased the extracellular acidification rate of the cells in a dose-dependent manner (EC(50) = 1.81 +/- 0.24 nM). The GnRH-stimulated acidification rate could be attenuated by protein kinase C (PKC) down-regulation, extracellular Ca2+ depletion, and the voltage-sensitive Ca2+ channel (VSCC) blocker nifedipine, indicating that the acidification response is activated by both Ca2+ and PKC-mediated pathways. Upon continuous exposure to 100 nM GnRH or periodic stimulation by 10 nM GnRH at 40 min intervals, homologous desensitization was more pronounced in the absence of extracellular Ca2+, suggesting that desensitization of GnRH activity may be mediated via depletion of intracellular Ca2+ stores. We have also compared the potency of eight GnRH analogs on alphaT3-1 cells. No acidification response was detected for GnRH free acid, consistent with the idea that the C-terminal amide is a critical structural determinant for GnRH activity. Replacement of Gly-NH(2) at the C-terminus by N-ethylamide dramatically reduced the EC(50) value, suggesting that substitution of the Gly-NH(2) moiety by N-ethylamide increases the potency of GnRH analogs. Substitution of Gly at position 6 by D-Trp significantly reduced the EC(50) value, whereas D-Lys at the same position slightly increased the EC(50) value, implying that either an aromatic amino acid or a non-basic amino acid at position 6 may be essential for potent GnRH agonists. In summary, our results demonstrate that the Cytosensor microphysiometer can be used to evaluate the actions of GnRH and GnRH analogs in alphaT3-1 cells in a real-time and noninvasive manner. This silicon-based microphysiometric system should provide new information on the structure-function studies of GnRH and is an invaluable tool for the screening of new GnRH agonists and antagonists in the future.


Subject(s)
Biosensing Techniques , Gonadotropin-Releasing Hormone/physiology , Amino Acid Sequence , Animals , Cell Line , Gonadotropin-Releasing Hormone/analogs & derivatives , Hydrogen-Ion Concentration , Structure-Activity Relationship
18.
Kaohsiung J Med Sci ; 16(5): 241-7, 2000 May.
Article in English | MEDLINE | ID: mdl-10969519

ABSTRACT

Intravenous electrocardiograph (IVECG) can correctly positioning the catheter tip by enlarging p wave as it is moved toward right atrium, and it is a safe, reliable and accurate technique. To evaluate the efficacy of wire-conducted IVECG signal and IVECG signal from the port with sodium bicarbonate (NaHCO3) flushed catheter and to compare those with conventional anatomy landmark method was the propose of this study. This prospective study was carried out in 216 patients who suffered from malignant diseases. The correct position of the catheter tip among these groups was confirmed as follows. In group 1 (n = 80), the anatomy landmark method and portable chest radiograph recognized the correct position. In group 2 (n = 72), IVECG signal was conducted from guide wire to identify the tip position. In group 3 (n = 64), IVECG signal was conducted from the port with NaHCO3 (0.8 mEq/mL) flushed catheter to ascertain the tip position. The patient characteristics did not differ significantly among the groups. The duration of operation was significantly (P < 0.001) longer in group 1 than in group 2 and group 3 (45.4 +/- 9.3 minutes vs 35.7 +/- 8.0 minutes and 35.2 +/- 9.7 minutes, respectively). Catheter tip placement times were shorter in group 2 and group 3 than in group 1 (5.3 +/- 2.9 minutes and 6.4 +/- 3.0 minutes vs 16.7 +/- 5.7 minutes, respectively); there was a statistically significant difference between the group 1 and group 2 and group 3 (p < 0.001). Nonetheless, the duration of operation and catheter tip placement time was similar in group 2 and group 3. Early and late complications within the subsequent 3 months showed no significant difference among groups. We concluded that IVECG signal conducted from guide wire obtained a similar efficiency to that signal from the port with NaHCO3 flushed catheter on positioning the catheter tip of the venous Port-A-Cath system. It is recommended to use these methods to facilitate implanting long-term central venous devices.


Subject(s)
Catheterization, Central Venous , Electrocardiography , Female , Humans , Male , Sodium Bicarbonate
19.
Kaohsiung J Med Sci ; 16(5): 255-60, 2000 May.
Article in English | MEDLINE | ID: mdl-10969521

ABSTRACT

Sevoflurane is used for pediatric ambulatory surgery due to its low blood solubility, rapid emergence, non-pungency and low airway irritability. Nevertheless, its tendency to induce agitation during emergence may offset its benefits. The following study was designed to evaluate the effects of intravenous (i.v.) tramadol (1 mg/kg) on the emergence from sevoflurane anesthesia. Forty ASA I children, ranging from 1 to 8 years old, scheduled for inguinal surgery, were randomized into two groups (Group S--control group, Group ST--i.v. tramadol, 20 in each group). The patients were first premedicated with oral atropine (0.01 mg/kg), then anesthesia was induced with i.v. application of thiamylal (3-4 mg/kg) and maintained with mask anesthesia with sevoflurane. Topical infiltration with 2-3 ml of 1% lidocaine was applied over skin incision area. I.v. tramadol (1 mg/kg) was given before the end of operation in Group ST. The emergence agitation was recorded on a visual analog scale (VAS, 0-10) by a blinded anesthesiologist in the PACU (postoperative anesthesia care unit), as well as the length of other recovery stages and complications after anesthesia. The age, weight, gender, and duration of surgery and anesthesia were similar in the two groups. The emergence agitation score (6.3 +/- 3.5 vs. 3.2 +/- 2.8, P < 0.05), incidences of agitation (VAS > 5, 55% vs 20%, P < 0.05), and postoperative pain (65% vs 30%, P < 0.05) were higher for the control group. I.v. Tramadol (1 mg/kg) before the end of operation reduced postoperative pain and the incidence and degree of emergence agitation from sevoflurane anesthesia in pediatric ambulatory surgery.


Subject(s)
Analgesics, Opioid/pharmacology , Anesthetics, Inhalation/pharmacology , Methyl Ethers/pharmacology , Psychomotor Agitation/prevention & control , Tramadol/pharmacology , Ambulatory Surgical Procedures , Anesthesia, Inhalation , Child , Child, Preschool , Female , Humans , Infant , Male , Sevoflurane
20.
Bioorg Med Chem Lett ; 10(15): 1649-52, 2000 Aug 07.
Article in English | MEDLINE | ID: mdl-10937716

ABSTRACT

Structural variation of the quinolizidine heterocycle of the influenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identification of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a plaque reduction assay.


Subject(s)
Antiviral Agents/pharmacology , Membrane Fusion/drug effects , Orthomyxoviridae/drug effects , Quinolizines/pharmacology , Salicylamides/pharmacology , Animals , Antiviral Agents/chemistry , Cell Line , Dogs , Orthomyxoviridae/physiology , Quinolizines/chemistry , Salicylamides/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL