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1.
Nat Commun ; 14(1): 6723, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37872193

ABSTRACT

Stimuli-responsive emulsions offer a dual advantage, combining long-term storage with controlled release triggered by external cues such as pH or temperature changes. This study establishes that thermo-responsive emulsion behaviour is primarily determined by interactions between, rather than within, interfaces. Consequently, the stability of these emulsions is intricately tied to the nature of the stabilizing microgel particles - whether they are more polymeric or colloidal, and the morphology they assume at the liquid interface. The colloidal properties of the microgels provide the foundation for the long-term stability of Pickering emulsions. However, limited deformability can lead to non-responsive emulsions. Conversely, the polymeric properties of the microgels enable them to spread and flatten at the liquid interface, enabling stimuli-responsive behaviour. Furthermore, microgels shared between two emulsion droplets in flocculated emulsions facilitate stimuli-responsiveness, regardless of their internal architecture. This underscores the pivotal role of microgel morphology and the forces they exert on liquid interfaces in the control and design of stimuli-responsive emulsions and interfaces.

2.
Zhonghua Yan Ke Za Zhi ; 58(8): 606-614, 2022 Aug 11.
Article in Chinese | MEDLINE | ID: mdl-35959605

ABSTRACT

Objective To prepare a biologically active amniotic membrane powder and explore its preservation conditions, and to evaluate the efficacy of the amniotic membrane (AM)-fibrin sealant (FS) cement made from the amniotic powder on the rabbit severe ocular surface alkali burn model. Methods Experimental research. Fresh AM was air-dried, cooled with liquid nitrogen, ground into amniotic powder and sterilized by radiation. The expression of transformed growth factor, nerve growth factor receptor (NGFR), hepatocyte growth factor (HGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) after preparation and 10, 20 and 30 days after storage at room temperature, 4 ℃ and -20 ℃ was tested and compared with that in the fresh AM. The AM-FS cement containing different concentrations of amniotic powder and no amniotic powder was diluted. Rabbit corneal epithelial cells were cultured for 72 hours. The effects of different concentrations of amniotic powder on epithelial cell growth were observed by light microscopy, and the amniotic powder concentration with the largest absorbance value at 450 nm was selected for subsequent animal experiments. Thirty-two right eyes of 32 rabbits as the severe ocular surface alkali burn model were divided using the random counting method into the AM-FS cement group, fresh AM transplantation group, FS group and antibiotic control group (8 rabbits each group) and given different interventions. After weekly observation of corneal repair, hematoxylin and eosin staining, immunohistochemical staining of monocyte chemotaxis protein 1 (MCP-1)and vascular endothelial growth factor (VEGF) were performed and detected by light microscopy at 28 days. The logFC values of the growth factor or receptor expression difference ratio were corrected by BH; the data were analyzed by t-test and analysis of variance. Results: The expression of TGF in the amniotic membrane powder compared with the fresh amniotic membrane group (logFC=-0.11), and the expression of NGFR (HGF, EGF, bFGF) was higher than that of the fresh amniotic membrane group (logFC=-2.07, 0.72, 0.46, 2.62; P<0.05); the expression of HGF, bFGF and EGF in amniotic membrane powder stored for 10 days and 20 days were no lower than fresh amniotic membrane; at 30 days, the expression of growth factors or receptors except HGF and bFGF were decreased, and HGF, bFGF and EGF were no less than 4 ℃ and -20 ℃.The maximum A value was obtained for 0.25 mg/ml of the amniotic membrane powder after 72 hours of the CEC culture 0.98±0.05. The corneal recovery was better in the AM-FS and fresh amniotic membrane transplant groups, with corneal turbidity scores of 3.75±0.46 and 3.50±0.46, respectively, on 28 days, lower than antibiotics (4.29±0.45) (t=2.480, 3.629; P=0.019, 0.001). The corneal neovascular area in the antibiotic control group was compared with the other three groups (t=4.040, 4.339, 2.820; all P<0.001); the corneal neovascular area in the AM-FS group was (9.88±0.20) and (18.96±0.18) mm2 at 7 and 28 days. The corneal neovascularization area at 7 and 28 days in the fresh AM group [(9.54±0.22) and (18.08±0.96) mm2] was smaller than the AM-FS group (t=3.085, 3.017, P=0.005, 0.005). Despite the tiny statistical difference (0.34, 0.88), there was no clinical difference. Hematoxylin and eosin staining showed corneal structures were intact in the AM-FS and fresh AM groups, the epithelial arrangement became normal, and the corneal healing was superior to the FS and antibiotic control groups. Immunohistochemistry showed that the positive expression of VEGF in the fresh AM group was weaker than that in the remaining three groups. MCP-1 was expressed to a similar extent in the AM-FS and fresh AM groups. Conclusions: The active cytokine had high expression and stable properties at room temperature. The AM-FS cement containing 0.25 mg/ml amniotic powder can promote the repair of corneal epithelium, reduce inflammatory reaction and corneal neovascularization after alkali burning in rabbit eyes.


Subject(s)
Burns, Chemical , Corneal Neovascularization , Amnion/metabolism , Amnion/transplantation , Animals , Anti-Bacterial Agents , Burns, Chemical/therapy , Corneal Neovascularization/metabolism , Eosine Yellowish-(YS)/metabolism , Epidermal Growth Factor/metabolism , Fibrin Tissue Adhesive/metabolism , Hematoxylin/metabolism , Powders/metabolism , Rabbits , Vascular Endothelial Growth Factor A/metabolism
3.
Zhonghua Bing Li Xue Za Zhi ; 49(10): 1031-1035, 2020 Oct 08.
Article in Chinese | MEDLINE | ID: mdl-32992418

ABSTRACT

Objective: To investigate the clinical manifestations, imaging features, histopathologic, immunohistochemical (IHC) and ultrastructure features of neuronal intranuclear inclusion disease (NIID). Methods: HE, IHC staining and EM were performed in cases of NIID diagnosed at the Department of Pathology, Jinling Hospital from 2018 to 2019. Results: Two cases were identified, including one male and one female; both patients were 76 years old. They were hospitalized because of nervous system dysfunction. MRI showed abnormal high signal intensity in corticomedullary junction of bilateral frontal lobes (male patient) and bilateral cerebral hemispheres (female patient). Light eosinophilic transparent inclusion bodies were seen in the nuclei of neurons in both rectal mucosa and cutaneous sweat glands, and these were positive for p62 by IHC. By scanning EM, the inclusion bodies in the sweat gland cells nuclei were round membranous structures consisting of 8-18 nm microfilaments. Conclusions: NIID is a rare, multi-system and slowly progressive neurodegenerative disease. Its clinical manifestations are highly diverse and easily misdiagnosed or missed. Neuroimaging can make a preliminary diagnosis. In the past, NIID can only be diagnosed through autopsy, and this study demonstrates that NIID can be confirmed through skin or rectal mucosal biopsy.


Subject(s)
Neurodegenerative Diseases/diagnostic imaging , Aged , Biopsy , Female , Humans , Intranuclear Inclusion Bodies , Magnetic Resonance Imaging , Male
4.
Hong Kong Med J ; 26(2): 95-101, 2020 04.
Article in English | MEDLINE | ID: mdl-32245911

ABSTRACT

INTRODUCTION: To compare the intermediate-term outcomes and patient-reported outcomes of robot-assisted laparoscopic prostatectomy (RALP) and radical external beam radiotherapy (RT) in Chinese patients with localised prostate cancer. METHODS: This was a retrospective study of patients with localised prostate cancer diagnosed between 2010 and 2011 and treated with either RALP or RT. Baseline patient and disease characteristics, post-treatment complications, and latest disease status were retrospectively collected from hospital records. For assessment of patient-reported outcomes, the Chinese version of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire was completed by the patients. RESULTS: Ninety three patients aged 58 to 84 years were recruited. Thirty patients were treated by RALP (32.3%), whereas 63 received RT (67.7%). The RALP group had significantly lower baseline prostate-specific antigen levels than the RT group (P<0.001). More patients who underwent RALP reported urinary incontinence (70.0% vs 3.2%, P<0.001), whereas more patients who underwent RT reported other voiding symptoms (87.3% vs 50.0%, P<0.001) and perirectal bleeding (36.5% vs 0%, P<0.001) during follow-up. Of the 85 patients who were still alive at the time of the study, 52 (61.2%) returned completed questionnaires. Patients who underwent RALP had poorer median (interquartile range) EPIC urinary summary scores than patients who underwent RT [81.5 (18.3) vs 88.9 (17.9), P=0.016]. Urinary function [75.9 (20.4) vs 93.6 (16.2), P<0.001] and incontinence [60.5 (31.8) vs 91.8 (14.5), P<0.001] were also significantly worse in the RALP group. The bowel and sexual domain scores were similar between the two groups. CONCLUSIONS: We found that RALP and RT were associated with different patterns of complications and patient-reported outcomes. Urinary incontinence was much more prevalent in the patients treated surgically. This may significantly affect patients' quality of life.


Subject(s)
Laparoscopy/adverse effects , Patient Reported Outcome Measures , Prostatectomy/adverse effects , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Aged , Aged, 80 and over , Hong Kong , Humans , Laparoscopy/methods , Male , Middle Aged , Prostate-Specific Antigen , Prostatectomy/methods , Quality of Life , Retrospective Studies , Robotics , Surveys and Questionnaires , Treatment Outcome , Urinary Incontinence/etiology
5.
Bone Joint J ; 101-B(4): 491-496, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30929488

ABSTRACT

AIMS: The aim of this study was to utilize a national paediatric inpatient database to determine whether obesity influences the operative management and inpatient outcomes of paediatric limb fractures. PATIENTS AND METHODS: The Kids' Inpatient Database (KID) was used to evaluate children between birth and 17 years of age, from 1997 and 2012, who had undergone open and closed treatment of humeral, radial and ulna, femoral, tibial, and ankle fractures. Demographics, hospital charges, lengths of stay (LOS), and complications were analyzed. RESULTS: Obesity was significantly associated with increased rates of open reduction and internal fixation (ORIF) for: distal humeral (odds ratio (OR) = 2.139, 95% confidence interval (CI) 1.92 to 3.44; p < 0.001); distal radius and ulna fractures (OR = 1.436, 95% CI 1.14 to 2.16; p < 0.05); distal femoral (OR = 2.051, 95% CI 1.69 to 3.60; p < 0.05); tibial and fibula shaft (OR = 2.101, 95% CI 2.10 to 3.50; p < 0.001); and ankle (OR = 1.733, 95% CI 1.70 to 2.39; p < 0.001). Older age was significantly associated with ORIF for all fractures (p < 0.05). LOS, hospital charges, and complications were significantly increased in obese patients following ORIF for upper and lower limb fractures (p < 0.05). CONCLUSION: Obese paediatric patients are more likely to undergo ORIF in both upper and lower limb fractures and have more inpatient complications. These findings may assist in informing obese paediatric fracture patients and their families regarding the increased risk for open operative fixation and associated outcomes. Cite this article: Bone Joint J 2019;101-B:491-496.


Subject(s)
Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Hand Injuries/surgery , Inpatients , Leg Injuries/surgery , Open Fracture Reduction/methods , Pediatric Obesity/complications , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Fractures, Bone/complications , Hand Injuries/complications , Humans , Incidence , Infant , Infant, Newborn , Leg Injuries/complications , Male , Postoperative Complications/epidemiology , Retrospective Studies , Treatment Outcome , United States/epidemiology
6.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 35(10): 765-767, 2017 Oct 20.
Article in Chinese | MEDLINE | ID: mdl-29294552

ABSTRACT

Objective: To investigate the clinical effect and safety of electroencephalographic biofeedback therapy in improving memory disorders in patientsin the recovery stage of acute severe toxic encephalopathy. Methods: A total of 52 patients in the recovery stage of acute severe toxic encephalopathy who were hospitalized in our hospital from March 2013 to December 2016 were enrolled and randomly divided into observation group with 27 patients and control group with 25 patients. Both groups were given the drugs to promote the metabolism of brain cells,and the patients in the observation group were given electroencephalographic biofeedback therapy in addition. The Chinese revised version of Wechsler Memory Scale Type A was used to measure memory ability before and after each course of treatment. The treatment outcome was evaluated for both groups. Results: There were no significant differences in the scores of long-term memory,short-term memory, immediate memory, and memory quotient between the two groups before treatment(P>0.05).After the first course of treatment ended, the observation group had significant increases in the scores of forward task,backward task,association,and memory quotient(P<0.05); compared with the control group, the observation group had a significant reduction in the score of backward task(P<0.05).After the second course of treatmentended, the observation group had significant increases in the scores offorward task,backward task,memorization of pictures,reproduction,association,comprehension,and memory quotient,and the control group had significant increases in the scores of reproduction,association,comprehension,and memory quotient(P<0.05); compared with the control group, the observation group had significant increases in the scores of forward task,backward task,memorization of pictures, reproduction, association, comprehension, and memory quotient(P<0.05).Two patients experiencedchest distress, palpitation, and dysphoria during treatment, which did not affect the treatment. Conclusion: Electroencephalographic biofeedback therapy has a certain effect in the treatment of memory disorders in patients with acute severe toxic encephalopathy.


Subject(s)
Memory Disorders/therapy , Neurofeedback/methods , Neurotoxicity Syndromes/complications , Acute Disease , Biofeedback, Psychology , Brain , Humans , Memory , Memory Disorders/physiopathology , Treatment Outcome
7.
Oncogene ; 34(37): 4821-33, 2015 Sep 10.
Article in English | MEDLINE | ID: mdl-25531323

ABSTRACT

Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-ß (TGF-ß) is known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN-) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-ß1 to mediate adoption of the CAF phenotype. This OPN-TGF-ß1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1 and TGF-ß1 dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN-MZF1-TGF-ß1 pathway.


Subject(s)
Breast Neoplasms/pathology , Cell Transformation, Neoplastic/metabolism , Fibroblasts/pathology , Mesenchymal Stem Cells/pathology , Neoplastic Stem Cells/pathology , Osteopontin/physiology , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Transformation, Neoplastic/genetics , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , MCF-7 Cells , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Osteopontin/pharmacology , Signal Transduction/drug effects , Signal Transduction/genetics , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Tumor Cells, Cultured
8.
Allergy ; 67(1): 131-7, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21951319

ABSTRACT

BACKGROUND: School personnel in contact with students with life-threatening allergies often lack necessary supports, creating a potentially dangerous situation. Sabrina's Law, the first legislation in the world designed to protect such children, requires all Ontario public schools to have a plan to protect children at risk. Although it has captured international attention, the differences a legislative approach makes have not been identified. Our study compared the approaches to anaphylaxis prevention and management in schools with and without legislation. METHODS: Legislated (Ontario) and nonlegislated (Alberta, British Columbia, Newfoundland and Labrador, and Quebec) environments were compared. School board anaphylaxis policies were assessed for consistency with Canadian anaphylaxis guidelines. Parents of at-risk children and school personnel were surveyed to determine their perspectives on school practices. School personnel's EpiPen5 technique was assessed. RESULTS: Consistency of school board policies with anaphylaxis guidelines was significantly better in a legislated environment (P=0.009). Parents in a legislated environment reported more comprehensive anaphylaxis emergency forms (P<0.001), while school personnel in nonlegislated environments reported more comprehensive forms (P=0.004). Despite school personnel in both environments receiving EpiPen5 training (>80%), suboptimal technique was commonly observed. However, school personnel in the legislated environment had better technique (P<0.001). CONCLUSION: Our results suggest that school boards in legislated environments have made greater efforts to support students at risk for anaphylaxis compared to nonlegislated environments. However, significant gaps exist in both environments, especially with respect to EpiPen5 administration, content, and distribution of anaphylaxis emergency forms, and awareness of school procedures by school personnel and parents.


Subject(s)
Anaphylaxis/prevention & control , School Health Services/legislation & jurisprudence , Schools/legislation & jurisprudence , Bronchodilator Agents/administration & dosage , Child , Epinephrine/administration & dosage , Guidelines as Topic , Humans , Ontario , Parents , Students
9.
Environ Geochem Health ; 31(6): 707-15, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19214759

ABSTRACT

This study was designed to investigate heavy metal (Cu, Zn, Pb, and Cd) contamination levels of soils, vegetables, and rice grown in the vicinity of the Dabaoshan mine, south China. The concentration of Cu, Zn, Pb, and Cd in paddy soil exceeded the maximum allowable concentrations for Chinese agricultural soil. The heavy metal concentrations (mg kg(-1), dry weight basis) in vegetables ranged from 5.0 to 14.3 for Cu, 34.7 to 170 for Zn, 0.90 to 2.23 for Pb, and 0.45 to 4.1 for Cd. The concentrations of Pb and Cd in rice grain exceeded the maximum permissible limits in China. Dietary intake of Pb and Cd through the consumption of rice and certain vegetable exceeded the recommended dietary allowance levels. The status of heavy metal concentrations of food crops grown in the vicinity of Dabaoshan mine and their implications for human health should be further investigated.


Subject(s)
Environmental Exposure , Food Contamination/analysis , Metals, Heavy/analysis , Oryza/chemistry , Soil Pollutants/analysis , Vegetables/chemistry , China , Environmental Monitoring , Humans , Mining , Risk Assessment , Spectrophotometry, Atomic
10.
J Clin Psychopharmacol ; 20(4): 435-44, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10917405

ABSTRACT

Oral codeine preparations, widely used for analgesia and cough suppression, are abused by some individuals for their mood-altering properties. The enzymatic O-demethylation of codeine is catalyzed by cytochrome P450 2D6 (CYP2D6), leading to the production of metabolites (morphine, morphine-6-glucuronide) that are pharmacologically more potent than codeine. A placebo-controlled, single-blind study was conducted to characterize the subjective effects of codeine associated with abuse liability and to determine the importance of metabolic O-demethylation to codeine abuse liability. Twelve non-drug-dependent subjects received oral administration of placebo and codeine 60, 120, and 180 mg, and a favorite dose (FD) was determined for each subject. The FD was readministered after pretreatment with placebo, 50 mg of quinidine (a specific, selective CYP2D6 inhibitor) once, or 50 mg of quinidine given four times a day for 4 days. Single-dose quinidine pretreatment significantly decreased the recovery of O-demethylated metabolites in plasma (p < 0.01) and resulted in a decrease in the positive (e.g., "high," p < 0.05) and negative (e.g., nausea, p < 0.05) subjective effects of codeine in both the FD120 and FD180 groups. Short-term quinidine pretreatment inhibited codeine O-demethylation more than did single-dose quinidine pretreatment (p < 0.01), and it decreased positive codeine effects in the FD120 group (N = 7), but unexpectedly not in the FD180 group (N = 5). These results suggest that the O-demethylated metabolites contribute substantially to the subjective effects and abuse liability of codeine.


Subject(s)
Codeine/adverse effects , Cytochrome P-450 CYP2D6 Inhibitors , Enzyme Inhibitors/therapeutic use , Narcotics/adverse effects , Opioid-Related Disorders/prevention & control , Quinidine/therapeutic use , Adult , Codeine/pharmacokinetics , Cytochrome P-450 CYP2D6/genetics , Dealkylation , Dose-Response Relationship, Drug , Female , Humans , Male , Narcotics/pharmacokinetics , Polymorphism, Genetic/genetics , Pupil/drug effects , Reproducibility of Results , Single-Blind Method , Time Factors
11.
Drug Metab Dispos ; 27(8): 924-30, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10421620

ABSTRACT

We investigated the enzymatic function, stability, and regional distribution of rat brain cytochrome P-450 (CYP) 2D1 activity. CYP2D1 is the homolog of human CYP2D6, a genetically variable enzyme that activates or inactivates many clinical drugs acting on the central nervous system (e.g., antidepressants, monoamine oxidase inhibitors, serotonin uptake inhibitors, and neuroleptics), drugs of abuse (e.g., amphetamine and codeine), neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3, 4-tetrahydroquinoline), and endogenous neurochemicals (e.g., tryptamine). The CYP2D family has been identified in rodent, canine, and primate brain. Conversion of dextromethorphan to dextrorphan by rat brain membranes was assayed by HPLC and was dependent on NADPH, protein concentration, and incubation time. Significant loss of activity was observed in some homogenizing buffers and after freezing of whole tissues or membrane preparations. Dextromethorphan (0.5-640 microM) metabolism was mediated by high- and low-affinity enzyme systems; K(m1) was 2.7 +/- 2.6 and K(m2) was 757 +/- 156 microM (n = 3 rats, mean +/- S.E.). The enzyme activity was significantly (p <.01) and stereoselectively inhibited by CYP2D1 inhibitors quinine and quinidine (not by CYP2C or CYP3A inhibitors), and by anti-CYP2D6 peptide antiserum (not by anti-CYP2C, -CYP2B, or -CYP3A antibodies). The enzymatic activity demonstrated significant brain regional variation (n = 10 regions, p <.001). These data characterize CYP2D1-mediated dextromethorphan metabolism in rat brain and suggest that localized metabolism of other CYP2D1 substrates (drugs, neurotoxins, and possibly endogenous compounds) within the brain will occur. In humans, CYP2D6 is genetically polymorphic; the variable expression of brain CYP2D6 may result in interindividual differences in central drug and neurotoxin metabolism, possibly contributing to interindividual differences in drug effects and neurotoxicity.


Subject(s)
Antitussive Agents/pharmacokinetics , Aryl Hydrocarbon Hydroxylases , Brain/enzymology , Cytochrome P-450 Enzyme System/metabolism , Dextromethorphan/pharmacokinetics , Alcohol Oxidoreductases , Animals , Antibodies, Blocking/pharmacology , Antitussive Agents/analysis , Cerebellum/drug effects , Cerebellum/metabolism , Chromatography, High Pressure Liquid , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P450 Family 2 , Dextromethorphan/analysis , Dextrorphan/analysis , Dextrorphan/pharmacokinetics , Kinetics , Liver/drug effects , Liver/metabolism , Male , Membranes/drug effects , Membranes/metabolism , NADP/metabolism , Neuroprotective Agents/analysis , Neuroprotective Agents/pharmacokinetics , Rats , Rats, Wistar
12.
J Pharmacol Exp Ther ; 280(3): 1374-82, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9067326

ABSTRACT

Humans that lack cytochrome P450 2D6 (CYP2D6) activity may have an altered risk of drug dependence or abuse because this enzyme is important in the metabolism of some drugs of abuse, including hydrocodone. In rats, hydrocodone conversion to hydromorphone is catalyzed by CYP2D1, the rat homolog of the human CYP2D6. To determine the impact of impaired hydromorphone formation on the behavioral effects of the parent compound, hydrocodone-induced analgesia and hyperactivity, hydrocodone discrimination and self-administration were examined in male Wistar rats, with or without pretreatment with CYP2D1 inhibitors (quinine and budipine). In vivo, quinine (20 mg/kg) and budipine (10 mg/kg) produced a marked suppression in brain and plasma hydromorphone levels detected after the peripheral administration of hydrocodone, thus confirming that the doses used suppressed CYP2D1 activity. In contrast, CYP2D1 inhibition had no impact on the analgesic or discriminative stimulus effects of hydrocodone, nor did this type of manipulation alter hydrocodone self-administration. The effects of quinine on the locomotor activating effects of hydrocodone were subtle at best. Because inhibition of CYP2D1 in this rat strain is proposed to be a useful animal counterpart for studying the impact of CYP2D6 polymorphism in humans, these data suggest that differences in CYP2D6 phenotype will have limited influence on the drug response to hydrocodone after nonoral administration. This has recently been verified in a study showing that inhibition of hydrocodone biotransformation to hydromorphone does not affect measures of abuse liability. Therefore, hydrocodone's behavioral effects are most likely attributable to its own intrinsic effects at mu opioid receptors.


Subject(s)
Behavior, Animal/drug effects , Cytochrome P-450 CYP2D6 Inhibitors , Enzyme Inhibitors/pharmacology , Hydrocodone/metabolism , Piperidines/pharmacology , Quinine/pharmacology , Animals , Brain/drug effects , Brain/metabolism , Hydrocodone/administration & dosage , Hydrocodone/pharmacology , Male , Rats , Rats, Wistar , Self Administration
13.
Eur J Drug Metab Pharmacokinet ; 22(4): 295-304, 1997.
Article in English | MEDLINE | ID: mdl-9512924

ABSTRACT

Comparison of 7-hydroxylation of coumarin, a CYP2A6 substrate, in human and African green and cynomolgus monkey liver microsomes was made by means of an HPLC assay with UV detection. In human liver microsomes, the Km and Vmax values for the metabolic conversion were 2.1 microM and 0.79 nmol/mg/min, respectively. While African green monkey showed Km and Vmax values of 2.7 microM and 0.52 nmol/mg/min, which were similar to human, higher Km and Vmax values were found in cynomolgus monkey. Coumarin 7-hydroxylation in human and African green monkey was selectively inhibited by methoxsalen and pilocarpine (CYP2A6 inhibitors) but not by other inhibitors, i.e. alpha-naphthoflavone (CYP1A1), orphenadrine (CYP2B6), sulfaphenazole (CYP2C9), quinidine (CYP2D6) and ketoconazole (CYP3A4). Immunoinhibition results supported CYP2A6 involvement in human and its homolog in monkey in coumarin 7-hydroxylation, as only anti-CYP2A6, but not CYP2B1, CYP2C13, CYP2D6, CYP2E1 or CYP3A antibodies, inhibited this conversion. African green monkey was found to be similar to human in catalytic activity of coumarin 7-hydroxylation and response to CYP2A6 inhibitors or antibody inhibition. However, the monkey CYP2A6 is not identical to the human in that Ki values were different, and differences were observed with some CYP2A6 inhibitors, such as nicotine and methoxsalen, suggesting that, under some circumstances, studies of nicotine kinetics and drug taking behavior in monkey may not be comparable to human.


Subject(s)
Anticoagulants/metabolism , Aryl Hydrocarbon Hydroxylases , Cytochrome P-450 Enzyme System/metabolism , Microsomes, Liver/enzymology , Mixed Function Oxygenases/metabolism , Adult , Animals , Antibodies, Monoclonal/pharmacology , Chlorocebus aethiops , Chromatography, High Pressure Liquid , Cytochrome P-450 CYP2A6 , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/immunology , Enzyme Inhibitors/pharmacology , Female , Humans , Hydroxylation , In Vitro Techniques , Kinetics , Macaca fascicularis , Male , Middle Aged , Mixed Function Oxygenases/antagonists & inhibitors , Mixed Function Oxygenases/immunology , Species Specificity , Spectrophotometry, Ultraviolet
14.
Eur J Drug Metab Pharmacokinet ; 22(4): 427-32, 1997.
Article in English | MEDLINE | ID: mdl-9512945

ABSTRACT

An improved HPLC method for analysis of methamphetamine (MAMP) and its metabolites in plasma was established, which features: high and reliable extraction recovery without loss of the analytes during solvent evaporation; no need for sample derivatization, and simultaneous analysis of MAMP, its N-demethylation and 4-hydroxylation metabolites. The major modification on the previous extraction procedure is addition of HCl to ethyl acetate extract prior to evaporation, resulting in significant increases in recovery, reproducibility and sensitivity. HPLC analysis is performed with an isocratic system on a C6 column. Samples are eluted with a mobile phase of acetonitrile-10 mM phosphate buffer containing 0.1% triethylamine (pH 6) at a flow rate of 1.0 ml/min, and monitored by a UV detector at a wavelength of 214 nm. All the analytes elute within 24 min. This method was successfully applied to the analysis of MAMP and its metabolites in rat plasma after MAMP dosing.


Subject(s)
Dopamine Uptake Inhibitors/blood , Methamphetamine/blood , Animals , Biotransformation , Chromatography, High Pressure Liquid , Dealkylation , Dopamine Uptake Inhibitors/pharmacokinetics , Hydrolysis , Hydroxylation , Male , Methamphetamine/pharmacokinetics , Rats , Rats, Wistar , Spectrophotometry, Ultraviolet
15.
Biochem Mol Biol Int ; 36(1): 113-22, 1995 May.
Article in English | MEDLINE | ID: mdl-7663405

ABSTRACT

Indole and isatin (2,3-dioxindole) analogues were studied as inhibitors of MAO-A and B. They exhibited reversible and competitive MAO inhibition. Three dimensional structures of the compounds tested were constructed and minimized using PC-based molecular graphic software. The QSAR analysis revealed the requirement of co-planar structure of substituents at C2 and C3 of indole ring for selective MAO-A inhibition, whilst type of bond was less essential. The presence of hydroxy group at C5 of isatin increased selectivity of MAO-A inhibition, however simultaneous insertion of substituents into both positions of indole ring (5-hydroxy-2-phenylindole) led to a decrease of MAO-A inhibition. The planar molecules demonstrating potent MAO-A inhibition have the average sizes 7 A in length and 6 A in width. The MAO B inhibition also depended on the sizes of planar molecules however distribution of electron density in the molecules was another precondition for the selective inhibition of the enzyme.


Subject(s)
Indoles/pharmacology , Mitochondria/enzymology , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase/metabolism , Animals , Humans , Indoles/chemistry , Indoles/metabolism , Isatin/analogs & derivatives , Isatin/chemistry , Isatin/metabolism , Isatin/pharmacology , Kinetics , Molecular Structure , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/metabolism , Rats , Structure-Activity Relationship
16.
Cephalalgia ; 15(2): 101-3, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7641242

ABSTRACT

The concept of dietary migraine as a clinical entity remains controversial. We review here such objective evidence that has been put forward for its existence. Red wine, in particular, is commonly alleged to initiate attacks in susceptible individuals. We discuss how some of its recently described pharmacological properties might trigger off the sequence of events leading to migrainous headache.


Subject(s)
Migraine Disorders/etiology , Wine/adverse effects , Clinical Trials as Topic , Double-Blind Method , Humans , Monoamine Oxidase Inhibitors/adverse effects
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 14(5): 268-70, 259, 1994 May.
Article in Chinese | MEDLINE | ID: mdl-7950208

ABSTRACT

UNLABELLED: The quality of life of 56 chronic renal failure (CRF) patients using two kinds of treatment has been observed. 36 of them were taken as Group A with BUN 21.62 +/- 5.96 mmol/L, Cr 528.63 +/- 176.3 mumol/L and Hb 65 +/- 13 g/L were treated with Baoyuan Dahuang Decoction consisted of Panax ginseng, Astragalus membranaceus, Cassia cinnamomi, Glycyrrhiza uralensis and Rheum palmatum. RESULT: Six symptoms were observed, that were: fatigue, lassitude in loin and legs, aversion of cold, anorexia, sexual dysfunction and mental depression. Five of them improved markedly, from 12.5 +/- 2.91 before treatment to 5.58 +/- 4.68 after treatment in terms of symptom scores, P < 0.001. Furthermore, dihydrothelin (E2), testosterone (T) and pregnendione (P) were regulated significantly, the elevated level of creatine phosphokinase (CPK) before treatment lowered to near normal. The other 20 patients, BUN 20.24 +/- 6.57 mmol/L, Cr 487.08 +/- 238.68 mumol/L and Hb 68 +/- 13g/L formed Group B using comprehensive treatment of Western medicine as control. The main drug was coated aldehyde oxystarch. After treatment, the symptoms didn't show marked improvement, symptom scores being 12.55 +/- 2.0 compared with 10.05 +/- 2.72 before treatment, P > 0.05. E2, T, P and CPK were of insignificant differences (P > 0.05); Hb remained almost unchanged, even though BUN and Cr lowered for 22% and 29% respectively. It is assumed that Baoyuan Dahuang decoction could improve CRF patients' quality of life, and the mechanism of which was not only to reduce the urea nitrogen, but also to adjust the anemia and regulate the membrane function.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Kidney Failure, Chronic/drug therapy , Adult , Astragalus propinquus , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/physiopathology , Kidney Function Tests , Male , Middle Aged , Quality of Life , Yang Deficiency/drug therapy
18.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 28(5): 272-4, 318, 1993 Sep.
Article in Chinese | MEDLINE | ID: mdl-8194413

ABSTRACT

A total of 38 seriously damaged posterior teeth were restored by cast metal prostheses, including onlays (with pulp chamber retainer and radicular retainer), cast dowelcore, two-piece dowel-core or cast dowel crown. As followed up for 6-48 months, 37 prostheses remained firm and sound, with perfect periphery seal, no secondary caries and pathological changes of peridontium were observed, The clinical consummate rate was 97%, The occlusal force of the restored teeth measured in 14 cases was 13.6-30.2 kg, which can satisfy the needs of masticatory function. The selection of retainers should be in accordance with the position and degree of crown damage of the posterior teeth. The key links guaranteeing smooth insertion and perfect periphery seal of cast metal prostheses were also pointed out.


Subject(s)
Crowns , Dental Restoration, Permanent , Adolescent , Adult , Child , Chromium Alloys , Dental Casting Technique , Female , Follow-Up Studies , Humans , Male , Middle Aged
19.
Zhonghua Bing Li Xue Za Zhi ; 22(4): 214-7, 1993 Aug.
Article in Chinese | MEDLINE | ID: mdl-8168179

ABSTRACT

Gangliogliomas are relatively rare tumors of the CNS in which ganglion cells and neuroglia coexist. 13 cases are reported, representing 0.61% of a series of 2,121 patients undergoing biopsy for CNS tumors. The clinical, radiological, pathological, electron microscopical and immunohistochemical features were evaluated with clinical follow-up. The age of the patients ranged from 3 to 51 years, including 8 males and 5 females. Duration of symptoms prior to surgery varied from 15 days to 12 years, the most common symptoms being seizures, headache, vomiting and motor disturbances. Computed tomographic scans found high density space-occupying mass in 6 patients and low density space-occupying mass in 3. Ten of the tumors originated form the cerebral hemispheres and three from the midline. The tumors were all sharply delineated and well defined from surrounding tissues. The tumor is generally firm. 8 patients are survived operation for 2-10 years. Neurons and glial cells in the tumor could be demonstrated by electron microscopy and immunohistochemical examination. Anaplastic transformation in the gliomatous component was found in one case. This series suggest that surgical removal of this neoplasm carries a good prognosis.


Subject(s)
Brain Neoplasms/pathology , Ganglioglioma/pathology , Adult , Brain Neoplasms/surgery , Cerebral Cortex , Child , Child, Preschool , Female , Ganglioglioma/surgery , Humans , Male , Middle Aged , Prognosis
20.
Zhonghua Zhong Liu Za Zhi ; 14(1): 45-7, 1992 Jan.
Article in Chinese | MEDLINE | ID: mdl-1327689

ABSTRACT

Paraffin sections of forty cases of human brain gliomas were immunohistochemically stained for five serum proteins by PAP techniques. In all gliomas P-Alb and Alb were present within the tumor interstitium. Cer was observed around tumor vessels and in highly anaplastic tumors consisting of polymorphic glioma cells. LDL and FN were almost restricted to blood vessels and necrotic areas. These results indicate that the occurrence and distribution of serum proteins in gliomas depend on the molecular weight of serum proteins, serum concentration and the differentiation of tumors. Serum proteins accumulated in peritumoral brain tissue, in reactive astrocytes and, occasionally, in neurons. Therefore, it can be assumed that in human brain gliomas serum proteins extravasate also mainly across tumorous blood vessels and reach the peritumoral tissue.


Subject(s)
Blood Proteins/analysis , Brain Neoplasms/metabolism , Glioma/metabolism , Astrocytoma/metabolism , Blood-Brain Barrier , Ceruloplasmin/analysis , Glioblastoma/metabolism , Humans , Immunohistochemistry , Lipoproteins, LDL/analysis , Serum Albumin/analysis
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