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1.
Zhonghua Nei Ke Za Zhi ; 61(10): 1144-1151, 2022 Oct 01.
Article in Chinese | MEDLINE | ID: mdl-36207969

ABSTRACT

Objective: To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM). Methods: A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP+) group, anti-HMGCR antibody positive (HMGCR+) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result: (1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP+, 8 (25.0%) with HMGCR+, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP+group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb (P<0.01). The axial muscle score was lower than the distal limb score (P<0.05).(3) Extramuscular manifestations of HMGCR+ group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups (P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP+ group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR+ group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion: IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP+ group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR+group were more prone to myotonia potential and CRDs.


Subject(s)
Autoimmune Diseases , Muscular Diseases , Myositis , Adult , Antibodies , Autoantibodies , Autoimmune Diseases/complications , Edema , Electrophysiology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Muscle, Skeletal/pathology , Muscular Diseases/diagnosis , Myositis/pathology , Necrosis/pathology , Polyesters , Proteomics , Retrospective Studies , Thigh/pathology
2.
J Water Health ; 20(6): 1017-1026, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35768974

ABSTRACT

There is considerable concern regarding antibiotic resistance in the water environment due to antibiotic residues from anthropogenic origins. The low antibiotic concentration in the water environment may promote the selection of antibiotic resistance. However, it is unclear how environmental factors affect resistance selection. We investigated the proliferation of quinolone-susceptible faecal bacteria (E. coli) exposed to low norfloxacin concentration (ng/L) at variable temperatures, exposure times, and carbon concentrations, simulating the conditions of the water environment. The induction of antibiotic resistance in thirteen E. coli isolates was more likely to occur at 37 °C. However, resistance also occurred at temperatures as low as 25 °C, provided a longer exposure time of 5 days. These results suggest that antibiotic resistance is more likely to be induced in regions where temperatures may reach 25-37 °C, such as tropical regions.


Subject(s)
Escherichia coli , Lakes , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Drug Resistance, Microbial , Lakes/microbiology , Microbial Sensitivity Tests , Water
3.
Clin Oncol (R Coll Radiol) ; 33(9): e403-e411, 2021 09.
Article in English | MEDLINE | ID: mdl-33715936

ABSTRACT

Radiotherapy and brachytherapy are the definitive treatments for locally advanced cervix cancer. The use of soft-tissue imaging, particularly magnetic resonance imaging, has enhanced their effectiveness and improved clinical outcomes. However, the use of magnetic resonance imaging is largely restricted to well-resourced centres in both the first and developing world and remains elusive to many less advantaged centres, particularly those in areas with a high burden of cervix cancer. Ultrasound is an accessible, affordable and accurate imaging modality that can be used throughout the brachytherapy procedure. Ultrasound is primarily used to ensure safe insertion of the applicator but can also be used to guide planning. The methods used to utilise ultrasound images for planning are described. Ultrasound is particularly useful as a verification aid to confirm applicator placement after patients are moved and transferred around the radiotherapy department. It can also be used to verify the dimensions of treatment volumes over the course of brachytherapy. There is a crucial unmet need for an accessible economical soft-tissue imaging modality in cervical brachytherapy. Ultrasound has the potential to meet this need.


Subject(s)
Brachytherapy , Uterine Cervical Neoplasms , Female , Humans , Ultrasonography , Ultrasonography, Interventional , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/radiotherapy
4.
Eur J Neurosci ; 50(3): 2401-2414, 2019 08.
Article in English | MEDLINE | ID: mdl-30019362

ABSTRACT

Previous work has shown that chronic administration of the dopamine D2/3 receptor agonist ropinirole invigorates performance on a rodent slot machine task (rSMT). This behavioural change appears superficially similar to the iatrogenic gambling disorder (GD) observed in a sub-set of patients with Parkinson's disease (PD), and has been associated with increased activation of the intra-cellular signalling proteins GSK3ß and CREB in the striatum. Here, we wanted to determine whether this response to ropinirole could be attenuated by targeting these signalling proteins, and if the loss of dopaminergic innervation characteristic of PD would alter ropinirole's effects on the rSMT. Male Long Evans rats were trained on the rSMT. Dopaminergic terminals innervating the dorsolateral striatum were then lesioned bilaterally using the neurotoxin 6-hydroxydopamine hydrochloride (6-OHDA). Subsequently animals were implanted with osmotic mini-pumps delivering ropinirole. Lastly, animals were given dietary lithium (Li+ ), to inhibit the activation of GSK3ß, or injections of the ß-adrenoceptor antagonist propranolol, which potently inhibits CREB as a secondary mechanism of action, and any changes in ropinirole-induced increases in compulsive-like engagement in the rSMT evaluated. Chronic ropinirole increased the number of trials animals completed, reproducing our original finding. This increase in task engagement was not altered in animals with 6-OHDA lesions, a putative model of early PD. In addition, the effects of ropinirole were not attenuated by administration of Li+ , but were ameliorated by propranolol. These data suggest that propranolol may represent a potential pharmacotherapy for the treatment of iatrogenic gambling.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Compulsive Behavior/drug therapy , Gambling/drug therapy , Propranolol/therapeutic use , Psychomotor Performance/drug effects , Adrenergic beta-Antagonists/pharmacology , Animals , Compulsive Behavior/psychology , Conditioning, Operant/drug effects , Conditioning, Operant/physiology , Gambling/psychology , Iatrogenic Disease , Male , Propranolol/pharmacology , Psychomotor Performance/physiology , Rats , Rats, Long-Evans
5.
Eur Rev Med Pharmacol Sci ; 22(20): 6880-6884, 2018 10.
Article in English | MEDLINE | ID: mdl-30402853

ABSTRACT

OBJECTIVE: Myeloma poses a serious risk for people's health and life quality. Molecular targeted treatment of myeloma emerges as a promising therapy. This study aimed to determine the effect of Sirtuin 6 on myeloma KM-HM_(31) cell aging and provide evidence for clinical treatment. MATERIALS AND METHODS: Myeloma KM-HM_(31) cell aging model induced by Carbamide peroxide (CP) was generated. Cells were transfected with Sirtuin 6 over-expression plasmid and specific siRNA. Western blot was used to study Sirtuin 6 expression, P53, P16, and Hippo in KM-HM_(31) cells. ß-galactosidase assay was applied to measure cell aging. Verteporfin inhibited Hippo signal pathway and measured aging of KM-HM_(31) cells. RESULTS: The levels of Sirtuin 6, aging protein P53, and P16 were remarkably elevated while Hippo expression was significantly inhibited in CP-induced KM-HM_(31) cells. Transfection of Sirtuin 6 over-expression plasmid enhanced Sirtuin 6 expression in KM-HM_(31) cells and potentiated cell aging with downregulation of Hippo protein. In contrast, a block of Sirtuin 6 resulted in the opposite effect. Moreover, Verteporfin inhibited Hippo signal pathway and enhanced CP-induced KM-HM_(31) cell aging, which contributed similar effect as Sirtuin 6 did. CONCLUSIONS: We showed that sirtuin 6 facilitates CP-induced myeloma cell KM-HM_(31) aging via suppressing Hippo.


Subject(s)
Multiple Myeloma/pathology , Protein Serine-Threonine Kinases/metabolism , Sirtuins/genetics , Cell Line, Tumor , Cellular Senescence , Down-Regulation , Hippo Signaling Pathway , Humans , Multiple Myeloma/genetics , Signal Transduction , Tumor Suppressor Protein p53/metabolism
6.
Clin Otolaryngol ; 42(2): 425-432, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27960043

ABSTRACT

OBJECTIVES: To assess the prognostic performance of a new N classification that incorporates the log odds of positive lymph nodes (LODDS) into the routinely used pathological N classification for oral squamous cell carcinoma (OSCC) patients. DESIGN: Retrospective cohort study utilising LODDS into pN category was performed, and the AJCC TNM stage and T-New N-M stage were compared with respect to 5-year disease-specific survival (DSS) rates. The discriminability was evaluated from the linear trend chi-square test, Akaike information criterion (AIC) and Harrell's c-statistic. SETTING: Medical centrer in Taiwan. PARTICIPANTS: A total of 463 patients received primary surgery and neck dissection between 2004 and 2013 for OSCC. MAIN OUTCOME MEASURES: The discriminability for 5-year DSS rates. RESULTS: The median follow-up period was 54 months, the mean patient age was 54 ± 11 years and 428 patients (92.4%) were male. The patients with higher LODDS had worse 5-year DSS rates. Incorporation of LODDS into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for 5-year DSS with a lower AIC (1883 versus 1897), and higher prediction accuracy (Harrell's c-statistic: 0.768 versus 0.764). CONCLUSIONS: By utilising a merger of the LODDS and pN classifications to create a new N classification has better discriminatory and predictive ability than pathological TNM staging and could help identify high-risk patients for intense adjuvant therapy.


Subject(s)
Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Lymphatic Metastasis/pathology , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/surgery , Female , Humans , Male , Middle Aged , Mouth Neoplasms/surgery , Neck Dissection , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Factors , Survival Analysis , Taiwan/epidemiology
7.
Psychopharmacology (Berl) ; 233(17): 3135-47, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27417550

ABSTRACT

RATIONALE: Rats, like humans, are susceptible to the reinforcing effects of reward-related stimuli presented within a compound stimulus array, putatively analogous to the so-called near-miss effect. We have previously demonstrated using a rodent slot machine task (rSMT) that the reward expectancy these stimuli elicit is critically mediated by the dopamine D4 receptor. D4 receptors are principally located in prefrontal regions activated during slot machine play in humans, such as the insular cortex. The insula has recently attracted considerable interest as it appears to play a crucial role in substance and behavioral addictions. However, the insula is a heterogeneous area, and the relative contributions of subregions to addictive behaviors are unclear. METHODS: Male Long Evans rats were trained to perform the rSMT, and then bilateral cannula targeting either the granular or agranular insula were implanted. The effects of inactivation and local administration of a D4 agonist were investigated. RESULTS: Temporary inactivation of the agranular, but not the granular insula impaired performance on the rSMT. In contrast, local infusion of the D4 agonist PD168077 into the agranular insula had no effect on task performance, but when administered into the granular insula, it improved animals' ability to differentiate winning from non-winning trials. The agranular insula may therefore modulate decision making when conflicting stimuli are present, potentially due to its role in generating a cohesive emotional percept based on both externally and internally generated signals, whereas the granular insular is not critical for this process. Nevertheless, D4 receptors within the granular insula may amplify the incentive salience of aversive environmental stimuli. DISCUSSION: These data provide insight into the neurobiological mechanism underpinning maladaptive reward expectancy during gambling and provide further evidence that D4 receptors represent a potential target for developing pharmacotherapies for problem gambling.


Subject(s)
Benzamides/pharmacology , Cerebral Cortex/drug effects , Decision Making/drug effects , Dopamine Agonists/pharmacology , Gambling/physiopathology , Piperazines/pharmacology , Receptors, Dopamine D4/agonists , Reward , Animals , Cerebral Cortex/physiopathology , Dopamine , Male , Rats , Rats, Long-Evans , Reinforcement, Psychology
8.
Hum Exp Toxicol ; 35(8): 808-17, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26429932

ABSTRACT

Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity.


Subject(s)
Acute Kidney Injury/prevention & control , Antineoplastic Agents/toxicity , Cisplatin/toxicity , Gastric Emptying/drug effects , Plant Extracts/therapeutic use , Vitis/chemistry , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Acute Kidney Injury/physiopathology , Animals , Antioxidants/metabolism , Fruit/chemistry , Fruit and Vegetable Juices , Gastric Mucosa/metabolism , Ghrelin/genetics , Kidney Function Tests , Male , Oxidative Stress/drug effects , Plant Extracts/isolation & purification , Rats, Wistar , Seeds/chemistry , Stomach/drug effects , Stomach/physiopathology
9.
Oncogene ; 34(40): 5141-51, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-25619834

ABSTRACT

Cullin 3 (Cul3)-family ubiquitin ligases use the BTB-domain-containing proteins for the recruitment of substrates, but the regulation of this family of ubiquitin ligases has not been completely understood. KLHL20 is a BTB-family protein and targets tumor suppressor promyelocytic leukemia protein (PML) and death-associated protein kinase (DAPK) to its kelch-repeat domain for ubiquitination and degradation. Here, we show that another BTB-kelch protein KLHL39 is recruited to the substrate-binding domain of KLHL20 but is not a substrate of Cul3-KLHL20 complex. Interestingly, KLHL39 does not bind Cul3 because of the absence of certain conserved residues in the BTB domain. Instead, KLHL39 blocks KLHL20-mediated ubiquitination of PML and DAPK by disrupting the binding of these substrates to KLHL20 as well as the binding of KLHL20 to Cul3. Through the two mechanisms, KLHL39 increases the stability of PML and DAPK. In human colon cancers, downregulations of KLHL39, PML and DAPK are associated with metastatic progression. Furthermore, preclinical data indicate that KLHL39 promotes colon cancer migration, invasion and survival in vitro and metastasis in vivo through a PML- and DAPK-dependent mechanism. Our study identifies KLHL39 as a negative regulator of Cul3-KLHL20 ubiquitin ligase and reveals a role of KLHL39-mediated PML and DAPK stabilization in colon cancer metastasis.


Subject(s)
Carrier Proteins/metabolism , Colonic Neoplasms/pathology , Death-Associated Protein Kinases/metabolism , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolism , Adaptor Proteins, Signal Transducing , Animals , Cell Line, Tumor , Colonic Neoplasms/metabolism , Female , Heterografts , Humans , Immunohistochemistry , Immunoprecipitation , Mice , Mice, Nude , Neoplasm Invasiveness , Neoplasm Metastasis , Promyelocytic Leukemia Protein , RNA Interference , RNA-Binding Proteins , Tissue Array Analysis , Transfection , Ubiquitination
10.
Eur J Pain ; 18(9): 1323-32, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24664661

ABSTRACT

BACKGROUND: Adrenomedullin (AM) belongs to the calcitonin gene-related peptide (CGRP) family. Our previous studies show that chronic exposure to morphine increases spinal AM bioactivity, contributing to the development and maintenance of morphine tolerance. This study investigated the possible involvement of AM in morphine-evoked gliosis. METHODS: Real-time polymerase chain reaction was performed to determine interleukin-1ß (IL-1ß), IL-6 and tumour necrosis factor-α (TNF-α) mRNAs in the spinal dorsal horn and cultured sensory ganglion explants. Immunohistochemistry was performed to identify spinal microglia and astrocytes. RESULTS: Repetitive intrathecal (i.t.) injection of morphine (20 µg) increased the expression of IL-1ß, IL-6 and TNF-α mRNAs in the spinal dorsal horn. The co-administration of the selective AM receptor antagonist AM22-52 (36 µg) markedly attenuated chronic morphine-evoked increase in IL-1ß and IL-6, but not TNF-α, mRNA levels. Exposure of cultured dorsal root ganglion (DRG) explants to morphine (3.3 µmol/L) for 6 days up-regulated IL-1ß and IL-6 mRNA expressions. The depletion of AM gene using small interfering RNA (siRNA) approach abolished morphine-evoked increase in IL-1ß and IL-6 syntheses in the cultured DRG. The blockade of AM receptors by i.t. AM22-52 also inhibited chronic morphine-evoked cell hypertrophy of microglia and astrocytes as well as an increase in OX-42 and GFAP (glial fibrillary acidic protein) immunoreactivities. Furthermore, the 6-day treatment with AM (10 µg, i.t.) induced morphological changes of microglia and astrocytes as well as an increase in IL-1ß, IL-6 and TNF-α mRNA levels in the spinal dorsal horn. CONCLUSION: The present study supports the idea that up-regulation of the pronociceptive mediator AM can recruit spinal glial cells, resulting in an increase in cytokines during chronic use of morphine.


Subject(s)
Adrenomedullin/metabolism , Cytokines/metabolism , Gliosis/metabolism , Morphine/pharmacology , Narcotics/pharmacology , Spinal Cord Dorsal Horn/metabolism , Adrenomedullin/administration & dosage , Adrenomedullin/pharmacology , Animals , Gliosis/chemically induced , Male , Morphine/administration & dosage , Narcotics/administration & dosage , Rats , Rats, Sprague-Dawley , Spinal Cord Dorsal Horn/drug effects , Up-Regulation
11.
Cell Death Differ ; 18(9): 1507-20, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21311567

ABSTRACT

Death-associated protein kinase (DAPK) is a key player in several modes of neuronal death/injury and has been implicated in the late-onset Alzheimer's disease (AD). DAPK promotes cell death partly through its effect on regulating actin cytoskeletons. In this study, we report that DAPK inhibits microtubule (MT) assembly by activating MARK/PAR-1 family kinases MARK1/2, which destabilize MT by phosphorylating tau and related MAP2/4. DAPK death domain, but not catalytic activity, is responsible for this activation by binding to MARK1/2 spacer region, thereby disrupting an intramolecular interaction that inhibits MARK1/2. Accordingly, DAPK(-/-) mice brain displays a reduction of tau phosphorylation and DAPK enhances the effect of MARK2 on regulating polarized neurite outgrowth. Using a well-characterized Drosophila model of tauopathy, we show that DAPK exerts an effect in part through MARK Drosophila ortholog PAR-1 to induce rough eye and loss of photoreceptor neurons. Furthermore, DAPK enhances tau toxicity through a PAR-1 phosphorylation-dependent mechanism. Together, our study reveals a novel mechanism of MARK activation, uncovers DAPK functions in modulating MT assembly and neuronal differentiation, and provides a molecular link of DAPK to tau phosphorylation, an event associated with AD pathology.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , MAP Kinase Signaling System , Microtubules/metabolism , Neurons/metabolism , Protein Serine-Threonine Kinases/metabolism , tau Proteins/metabolism , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Animals , Cell Differentiation , Cell Line , Death-Associated Protein Kinases , Drosophila , Enzyme Activation , Humans , Mice , Microtubules/ultrastructure , Neurons/ultrastructure , Phosphorylation
12.
Transplant Proc ; 42(10): 4217-20, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21168668

ABSTRACT

Although only 10% of islet transplant recipients maintain insulin independence, 80% of them are C-peptide positive at 5 years. To better understand the fate of transplanted islets, a magnetic resonance imaging (MRI) technique has been used to detect superparamagnetic iron oxide (SPIO)-labeled transplanted islets. Recently, we successfully used a novel MRI contrast agent, chitosan-coated SPIO (CSPIO) nanoparticles, to monitor mouse islet isografts for 18 weeks after transplantation. In the present study, we tested whether CSPIO could be applied to monitor islet allografts, which are supposedly rejected without immune interventions. Male C57BL/6 and Balb/c mice were used as donors and recipients of islet transplantation, respectively. After overnight incubation with or without CSPIO (10 µg/mL), 300 C57BL/6 islets were transplanted under the left kidney capsule of each Balb/c mouse. Starting from day 10 after transplantation, 3.0-Tesla MRI of the recipients was performed weekly. Four mice were followed for ≥38 days. At 38 and 45 days, 1 islet graft was removed for insulin and Prussian blue staining, respectively. From days 10 to 45 after transplantation, CSPIO-labeled islet grafts were visualized on MRI scans as sustained distinct hypointense spots homogeneously located at the upper pole of left kidney, the site of transplantation. At days 38 and 45, the histology of CSPIO-labeled islet grafts revealed insulin and iron staining colocalized in the same areas. Our results in a mouse allotransplantation model indicated that CSPIO-labeled islets survived as long as 45 days with positive MRI.


Subject(s)
Islets of Langerhans Transplantation , Magnetic Resonance Imaging/methods , Animals , Immunohistochemistry , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Transplantation, Homologous
13.
Int J Tuberc Lung Dis ; 14(7): 806-18, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20550762

ABSTRACT

OBJECTIVE: To compare the effects of food and antacids on the bioavailability of first-line anti-tuberculosis drugs. METHOD: Systematic search of electronic databases PubMed (January 1950-May 2009), and the Cochrane Library database (January 1974-May 2009), including the Cochrane Centre register of controlled trials, and ongoing trials from research registers using key terms 'food', 'antacids', 'meal', 'controlled trial', 'diet', and the first-line anti-tuberculosis drugs isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA). Meta-analysis was performed using RevMan software 5 to assess the impact of food or antacids on the maximum plasma concentrations (C(max)) and area under the plasma concentration time curve (AUC) of anti-tuberculosis drugs. RESULTS: Twelve trials involving 157 patients were included in the meta-analysis. The overall effects showed that food significantly reduced the C(max) mean difference (C(max) MD; C(max) MD -1.42, 95%CI -1.56--1.28, P < 0.00001) and AUC (C(max) MD -3.33, 95%CI -4.05--2.62, P < 0.00001) of INH but antacids did not. Food also significantly reduced the C(max) MD (C(max) MD -2.47, 95%CI -3.30--1.64, P < 0.00001) but not the AUC of RMP. Antacids had no effect on the C(max) MD or AUC of RMP. The C(max) and AUC of PZA were unaffected by both food and antacids. Both food and antacids reduced the C(max) but not the AUC of EMB. CONCLUSION: From a pharmacokinetic point of view, it seems that the better option for patients with gastrointestinal upsets during chemotherapy would be to add antacids rather than dosing with meals.


Subject(s)
Antacids/pharmacology , Antitubercular Agents/pharmacokinetics , Food-Drug Interactions , Antitubercular Agents/administration & dosage , Area Under Curve , Biological Availability , Clinical Trials as Topic , Drug Interactions , Humans
14.
Clin Exp Dermatol ; 34(8): e636-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20073092

ABSTRACT

A 68-year-old Chinese woman presented with generalized reticulated dark-brown hyperpigmentation on the trunk, face and limbs, oral Wickham's striae, sparse scalp hair and dark-red reticulated streaks on the occiput of the head and on the neck, some dark-red to violaceous papules on the face, scalp and flanks, light-yellow, deep-seated papules on the palms and soles, and small porcelain-white papules on the dorsal and lateral fingers. The histological features were consistent with the diagnosis of lichen planus (LP). To our knowledge, LP-induced generalized reticulated hyperpigmentation is very rare and this is the first report of the clinical features on the fingers, palms and soles.


Subject(s)
Foot Dermatoses/pathology , Hand Dermatoses/pathology , Hyperpigmentation/pathology , Lichen Planus/pathology , Aged , Diagnosis, Differential , Female , Humans , Hyperpigmentation/etiology , Immunohistochemistry , Lichen Planus/complications , Scalp/pathology
15.
Food Chem Toxicol ; 45(11): 2171-8, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17619074

ABSTRACT

After a long-term culture in (-)-epigallocatechin gallate (EGCG, 20 microM), a major constituent of green tea, human gastric AGS cells developed 2.2-fold resistance to EGCG. The resistant AGS (AGS-R) cells were cross-resistant to several N-methylcarbamate insecticides, which are among the major control agents for pest insects in Taiwan. The AGS-R cells also showed protective effects against both the cytotoxicity and DNA damage induced by one of the mutagenic derivatives of N-methylcarbamate insecticide, N-nitroso methomyl, which is known to target the mammalian gastric tract. Therefore, acquisition of resistance by AGS cells through chronic exposure to EGCG implies that the tea-drinking habit of the Taiwanese is probably beneficial for the health of the gastric tract. In addition, AGS-R cells were cross-resistant to sodium arsenite and hydrogen peroxide, indicating that tolerance to oxidative stress might play a role in the development of resistance described in this investigation.


Subject(s)
Catechin/analogs & derivatives , Environmental Pollutants/adverse effects , Stomach/cytology , Arsenites/adverse effects , Carbamates , Catechin/pharmacology , Cell Line, Tumor , Cytoprotection , Dose-Response Relationship, Drug , Humans , Hydrogen Peroxide/adverse effects , Insecticides/adverse effects , Reactive Oxygen Species , Sodium Compounds/adverse effects
16.
J Phys Chem B ; 110(44): 22097-102, 2006 Nov 09.
Article in English | MEDLINE | ID: mdl-17078645

ABSTRACT

Extreme osmotic compression of nanoemulsion droplets, achieved by ultracentrifugation, can create solidlike biliquid foams without causing significant droplet coalescence. Using small-angle neutron scattering (SANS), we probe the structure of a uniform silicone oil-in-water nanoemulsion stabilized by sodium dodecyl sulfate over a wide range of volume fractions, phi, up to and beyond the limit associated with maximal random jamming of spheres, phiMRJ = 0.64. Although some features in the structure can be understood at lower phi using simple predictions for hard spheres, the anionic repulsion and deformability of the droplet interfaces creates departures from these predictions at higher phi. For phi near and beyond phiMRJ, the effective structure factor, Seff, as a function of wavenumber, q, exhibits a primary peak that is subunity. We speculate that this striking feature is due to the deformation of the droplets into nonspherical shapes as the system begins to approach the limit of a random array of nanoscopic thin films, Plateau borders, and vertexes characteristic of a polyhedral foam.

17.
Phys Rev Lett ; 96(1): 015501, 2006 Jan 13.
Article in English | MEDLINE | ID: mdl-16486472

ABSTRACT

Using time-resolved small angle neutron scattering, we have measured the wave-number-dependent structure factor S(q) of monodisperse nanoemulsions that aggregate and gel after we suddenly turn on a strong, short-range, slippery attraction between the droplets. At high q, peaks in S(q) appear as dense clusters of droplets form, and S(q) increases strongly toward low q, as these dense clusters become locked into a rigid gel network, despite the fluidity of the films between the droplets. The long-time high-q structure of nanoemulsion gels formed by slippery diffusion-limited cluster aggregation is universal in shape and remarkably independent of the droplet volume fraction, phi.

18.
Br J Surg ; 92(11): 1382-7, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16044411

ABSTRACT

BACKGROUND: The aim of this study was to investigate the hypothesis that outcome following concomitant airway resection is superior to that after shaving of the tumour in patients with airway invasion of thyroid carcinoma. METHODS: The records of 34 patients with thyroid cancer with airway invasion were reviewed retrospectively. In addition to total thyroidectomy, airway resection was performed in 18 patients (group 1), whereas the tumour was shaved away from the airway in the other 16 patients (group 2). 131I was used as postoperative adjuvant therapy in all patients. Metastasis and recurrence of the primary lesion were determined by 131I whole-body scans, serum thyroglobulin levels, and computed tomography or ultrasonography of the neck. RESULTS: In group 1, two anastomotic dehiscences resulted in one death. Patients in group 2 had a higher rate of local recurrence (relative risk 8.0, P = 0.013) and earlier recurrence (mean(s.e.m.) 2.6(0.8) versus 7.0(1.1) years; P = 0.026) than those in group 1. Median survival was 5.8 and 4.3 years in the 18 patients of group 1 and 16 patients of group 2 (P = 0.259), and the respective 5-year survival rates were 88 and 84 per cent (P = 0.783). CONCLUSION: Aggressive airway resection can minimize local recurrence of thyroid carcinoma with airway invasion.


Subject(s)
Bronchial Neoplasms/surgery , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Bronchial Neoplasms/mortality , Bronchial Neoplasms/pathology , Child , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/prevention & control , Survival Analysis , Thyroid Neoplasms/mortality , Thyroid Neoplasms/pathology , Treatment Outcome
19.
Phys Rev E Stat Nonlin Soft Matter Phys ; 71(4 Pt 1): 040801, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15903650

ABSTRACT

We have performed small angle neutron scattering measurements (SANS) on dilute aqueous dispersions of polymer microgel particles as a function of temperature, T . The microgel particles are spherical crosslinked assemblies of a loose gel network of a poly-N-isopropylacrylamide (NIPAM) polymer. When the temperature is raised beyond a critical temperature, T(lc) approximately 32 degrees C , the polymer becomes more strongly attracted to itself than the solvent, and the microgel particles contract. The measured form factor, F (q) , for dilute suspensions of uniform microgel particles exhibits many peaks that are characteristic of solid polymer nanospheres. The position and amplitude of the peaks as a function of wave number, q , provide insight into the density profile of poly-NIPAM within the microgels. These peaks can be described well over a wide range of temperature by a model of the polymer density within the particles that is constant up to an inner radius, R1 , and decreases linearly to zero at an outer radius, R2 .

20.
J Chem Phys ; 122(13): 134703, 2005 Apr 01.
Article in English | MEDLINE | ID: mdl-15847485

ABSTRACT

We use extreme shear to create a dispersion of nanoscale droplets of silicone oil in an immiscible water phase containing an anionic surfactant sodium dodecylsulfate. Using centrifugal size fractionation, we obtain nanoemulsions having a well-defined average radius of a=75 nm. We measure the structure of concentrated nanoemulsions over a wide range of volume fractions, 0

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