ABSTRACT
AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
Subject(s)
Alzheimer Disease/epidemiology , Dementia/epidemiology , Parity/physiology , Aged , Aged, 80 and over , China/epidemiology , Cohort Studies , Europe/epidemiology , Female , Geriatric Psychiatry , Humans , Incidence , Independent Living , Middle Aged , Pregnancy , Proportional Hazards Models , Republic of Korea/epidemiology , Risk Factors , Socioeconomic FactorsABSTRACT
OBJECTIVES: The objective of this study was to investigate secular trends in adolescent health status and healthcare consultations. STUDY DESIGN: The design of this study is cross-sectional comparisons of population survey outcomes. METHODS: Canadian national population data from 2007 to 2016 (T1 N = 14,223; T2 N = 14,247; T3 N = 13,532; T4 N = 13,184; T5 N = 11,122; Total N = 66,308) were examined to find trends in health diagnosis (chronic illnesses and mental disorders) and healthcare consultation (general health practitioners and mental health professionals). Controlling demographics, Multivariate analysis of covariances (MANCOVAs) and correlations were carried out to compare differences by age group (A1: 12-14 years N = 25,180; A2: 15-17 years N = 25,825; A3: 18-19 years N = 15,303) and gender (girls N = 32,388; boys N = 33,920) across survey years. RESULTS: Steady increases were found in diagnosed mental disorders and consultations with a mental health professional (MP) for girls, while chronic illnesses remained stable and general practitioner consultations declined for all adolescents over these years. Gender disparity in MP consultations grew with age, much more in recent years, whereas chronic illness diagnoses curved down for all in midadolescence. More integrated relations between health status and healthcare utilization were noted in T5 than in T1. CONCLUSIONS: Differential secular trends were shown for adolescent physical versus mental health statuses and relevant healthcare consultations. Although girls' and older adolescents' mental health declined over the years, a positive direction was also found for improved awareness of mental health.
Subject(s)
Adolescent Health , Delivery of Health Care/organization & administration , Health Status , Mental Disorders/epidemiology , Mental Health/statistics & numerical data , Referral and Consultation/statistics & numerical data , Adolescent , Canada/epidemiology , Chronic Disease , Cross-Sectional Studies , Female , Humans , Male , Surveys and QuestionnairesABSTRACT
Transportation of actinides through the geosphere is facilitated by complexation with organic ligands dissolved in groundwater. Carboxylic groups can interact directly with actinide ions and are found among the most abundant organic ligands in alkaline aquatic systems like underground water. In this study, the complexation of organic carboxylic groups with Am(iii) was investigated by monitoring the interactions of Am(iii) with oxalate (Ox), the simplest dicarboxylate ligand, in solution. UV-Vis spectrophotometry coupled with a liquid waveguide capillary cell (100 cm optical path-length) and time-resolved laser fluorescence spectroscopy were employed for quantitative detection of the respective Am(iii)-Ox species. Increasing the Ox concentration caused significant spectral changes, i.e., red-shifts in both the absorption and luminescence maxima with increased molar absorption coefficients, enhanced luminescence intensities, and prolonged luminescence lifetimes. Individual spectra of AmOx+(aq), Am(Ox)2-(aq), and Am(Ox)33-(aq) were resolved by deconvolution of the absorption spectra, with apparent formation constants of log ß1,1 = 5.34 ± 0.05, log ß1,2 = 9.14 ± 0.18, and log ß1,3 = 11.49 ± 0.30, respectively, in I = 0.1 M NaClO4 and 0-30 mM Na2Ox. The absorption and luminescence spectral changes suggest bidentate complexation of Ox with Am(iii) via inner-sphere interactions. The geometry of the Am(iii)-Ox complexes was optimized by density functional theory, where the bonding characteristics were in good agreement with the experimental results. Thorough spectroscopic characterization enabled speciation of the Am(iii)-Ox complexes and determination of their formation constants. This spectroscopic approach is generally applicable in the investigation of molecular interactions between Am(iii) and various ligands in aqueous solution.
ABSTRACT
BACKGROUND AND PURPOSE: The occult changes in normal-appearing white matter (NAWM) were investigated and compared amongst patients with neuromyelitis optica spectrum disorder (NMOSD), patients with multiple sclerosis (MS) and healthy controls (HCs) by applying tract-based spatial statistics to diffusion tensor imaging (DTI) data. METHODS: Diffusion tensor imaging was performed with a 3-T scanner in 93 patients with NMOSD, 53 patients with MS and 43 HCs. Voxel-wise statistical analyses of the DTI data were performed using tract-based spatial statistics. RESULTS: Compared to HCs, patients with NMOSD had significantly lower mean global fractional anisotropy, higher mean diffusivity and radial diffusivity, and no significant differences in axial diffusivity in their NAWM. Patients with MS demonstrated significantly lower mean global fractional anisotropy and higher mean diffusivity, axial diffusivity and radial diffusivity in the NAWM than did patients with NMOSD and HCs. Compared to patients with NMOSD, patients with MS had NAWM damage that was more extensive, particularly in the inferior cerebellar peduncle, external capsule, cingulum, superior fronto-occipital fasciculus and uncinate fasciculus. CONCLUSIONS: Using DTI, widespread occult damage was demonstrated in the NAWM of patients with NMOSD. However, the NAWM was less affected in patients with NMOSD than it was in patients with MS; specifically, the axonal injuries and diffusion abnormalities in the association fibers were more severe in patients with MS than they were in patients with NMOSD.
Subject(s)
Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Neuromyelitis Optica/diagnostic imaging , White Matter/diagnostic imaging , Adult , Anisotropy , Brain/diagnostic imaging , Diffusion Tensor Imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND AND PURPOSE: We investigated changes in deep gray matter (DGM) volume and its relationship to cognition and clinical factors in a large cohort of patients with neuromyelitis optica spectrum disorder (NMOSD) and compared them with results from multiple sclerosis (MS). METHODS: Brain magnetic resonance imaging (3 Tesla) and clinical data from 91 patients with NMOSD, 52 patients with MS and 44 healthy controls (HCs) were prospectively evaluated. Differences in DGM volumes were compared among groups. The relationships between DGM atrophy and clinical variables were also analysed. RESULTS: Patients with NMOSD exhibited significantly reduced thalamic volumes compared with HCs (P = 0.029), although this atrophy was less severe than that seen in patients with MS (P < 0.001). DGM atrophy was restricted to the thalamus in NMOSD, but it was broadly distributed in MS. Patients with NMOSD with cognitive impairment (CI) exhibited more severe thalamic atrophy than those with cognitive preservation (P = 0.017) and HCs (P = 0.003), whereas patients with MS with CI revealed DGM atrophy across the entire structure, with the exception of the bilateral pallidum, left hippocampus and amygdala, relative to HCs. The Expanded Disability Status Scale score was correlated with thalamic atrophy in both NMOSD and MS. Patients with NMOSD with brain lesions demonstrated more severe thalamic atrophy than did those without brain lesions and HCs (P < 0.001). CONCLUSIONS: The DGM atrophy was less severe and more selectively distributed in NMOSD than in MS. Thalamic atrophy was associated with clinical disability, including CI, in both NMOSD and MS.
Subject(s)
Gray Matter/pathology , Multiple Sclerosis/pathology , Neuromyelitis Optica/pathology , Adult , Atrophy , Cognitive Dysfunction/pathology , Cognitive Dysfunction/psychology , Disability Evaluation , Female , Globus Pallidus/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/psychology , Neuromyelitis Optica/psychology , Prospective Studies , Thalamus/pathologyABSTRACT
BACKGROUND AND PURPOSE: Studies on cortical involvement and its relationship with cognitive function in patients with neuromyelitis optica spectrum disorder (NMOSD) remain scarce. The objective of this study was to compare cortical thickness on magnetic resonance imaging (MRI) between patients with NMOSD and multiple sclerosis (MS) and to investigate its relationship with clinical features and cognitive function. METHODS: This observational clinical imaging study of 91 patients with NMOSD, 52 patients with MS and 44 healthy controls was conducted from 1 December 2013 to 30 April 2015 at the institutional referral center. Three tesla MRI of the brain and neuropsychological tests were performed. Cortical thickness was measured using three-dimensional surface-based analysis. RESULTS: Both sets of patients exhibited cortical thinning throughout the entire brain cortex. Patients with MS showed a significantly greater reduction in cortical thickness over broad regions of the bilateral frontal and parieto-temporal cortices and the left precuneus compared to those with NMOSD. Memory functions in patients with MS were correlated with broad regional cortical thinning, whereas no significant associations were observed between cortical thickness and cognitive function in patients with NMOSD. CONCLUSIONS: Widespread cortical thinning was observed in patients with NMOSD and MS, but the extent of cortical thinning was greater in patients with MS. The more severe cortical atrophy may contribute to memory impairment in patients with MS but not in those with NMOSD. These results provide in vivo evidence that the severity and clinical relevance of cortical thinning differ between NMOSD and MS.
Subject(s)
Brain/pathology , Cognition/physiology , Neuromyelitis Optica/pathology , Adult , Atrophy/diagnostic imaging , Atrophy/pathology , Atrophy/psychology , Brain/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuromyelitis Optica/diagnostic imaging , Neuromyelitis Optica/psychology , Neuropsychological TestsABSTRACT
BACKGROUND: This study evaluated the effects of allopurinol (ALP), a xanthine oxidase inhibitor, and apocynin (APC), a NADPH oxidase inhibitor, administered alone or together, on kidney damage caused by renal ischemia-reperfusion (IR) in rats. METHODS: Thirty rats were randomly assigned to 5 groups. Group 1 was a sham group. Group 2 was the renal IR control group (30-min ischemia followed by 24-h reperfusion). In groups 3 and 4, ALP or APC, respectively, was administered 1 h before the ischemia. In group 5, ALP and APC were co-administered. Blood urea nitrogen (BUN) and serum creatinine (Cr), renal tissue malondialdehyde (MDA) and superoxide dismutase (SOD), and histological changes were evaluated. RESULTS: A significant increase in BUN and Cr level, and histological damage was seen in the IR control group, indicating renal injury. Elevated MDA and decreased SOD levels in the IR control group demonstrated that renal damage occurred through oxidative stress. Pretreatment with ALP or APC alone or together prevented IR-induced renal damage. However, there was no significant difference between treatment with a single drug and co-administration of ALP and APC. CONCLUSIONS: The use of ALP and/or APC before ischemia may be beneficial to ameliorate renal IR injury.
Subject(s)
Acetophenones/administration & dosage , Allopurinol/administration & dosage , Enzyme Inhibitors/administration & dosage , Kidney/drug effects , Reperfusion Injury/prevention & control , Animals , Blood Urea Nitrogen , Creatinine/blood , Drug Therapy, Combination , Ischemia/pathology , Ischemic Preconditioning/methods , Kidney/blood supply , Kidney Diseases/pathology , Kidney Function Tests , Male , Malondialdehyde/metabolism , Oxidative Stress , Random Allocation , Rats , Superoxide Dismutase/metabolismABSTRACT
Absorption spectra of very small metal clusters exhibit individual peaks that reflect the discreteness of their localized electronic states. With increasing size, these states develop into bands and the discrete absorption peaks give way to smooth spectra with, at most, a broad localized surface-plasmon resonance band. The widely accepted view over the last decades has been that clusters of more than a few dozen atoms are large enough to have necessarily smooth spectra. Here we show through theory and experiment that for the ubiquitous thiolate cluster compound Au144(SR)60 this view has to be revised: clearly visible individual peaks pervade the full near-IR, VIS and near-UV ranges of low-temperature spectra, conveying information on quantum states in the cluster. The peaks develop well reproducibly with decreasing temperature, thereby highlighting the importance of temperature effects. Calculations using time-dependent density-functional theory indicate the contributions of different parts of the cluster-ligand compound to the spectra.
Subject(s)
Models, Chemical , Nanoparticles/chemistry , Organogold Compounds/chemistry , Quantum Theory , Sulfur Compounds/chemistry , Cyclohexanes , Cyclopentanes , Kinetics , Mass Spectrometry/methodsABSTRACT
The present study aimed at investigating the effectiveness and tolerability of -bupropion hydrochloride extended release (XL) in major depressive disorder (MDD) patients with atypical features (AF).51 patients were prescribed bupropion XL for 8 weeks (6 visits: screening, baseline, weeks 1, 2, 4 and 8). The primary efficacy measure was a change of the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) from baseline to endpoint. Secondary efficacy measures included the SIGH-SAD atypical symptoms subscale, Clinical Global Impression-Severity (CGI-S), Sheehan Disability Scale (SDS) and Epworth Sleepiness Questionnaire (ESQ). Response or remission was defined as ≥50% reduction or ≤7 in SIGH-SAD total scores, respectively, at end of treatment.The HAM-D-29 total score reduced by 55.3% from baseline (27.3±6.5) to end of treatment (12.2±6.3) (p<0.001). Atypical symptom subscale scores also reduced by 54.5% from baseline (9.2±3.0) to end of treatment (4.2±2.8) (p<0.001). At the end of treatment, 24.4% (n=10) and 51.2% (n=21) subjects were classified as remitters and responders, respectively. The most frequently reported AEs were headache (13.7%), dry mouth (11.8%), dizziness (9.8%), and dyspepsia (9.8%).Our preliminary study indicates that bupropion XL may be beneficial in the treatment of MDD with atypical features. Adequately powered, randomized, double-blind, placebo-controlled trials are necessary to determine our results.
Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Bupropion/therapeutic use , Depressive Disorder, Major/drug therapy , Adult , Antidepressive Agents, Second-Generation/administration & dosage , Antidepressive Agents, Second-Generation/adverse effects , Bupropion/administration & dosage , Bupropion/adverse effects , Delayed-Action Preparations/adverse effects , Depressive Disorder, Major/diagnosis , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Single-Blind MethodABSTRACT
OBJECTIVE: Transfers to adult care can be problematic, resulting in postponement due to the protective nature of pediatric care and patient dependency. It is unknown whether these findings apply specifically to urology patients. Our department is taking part in a national general transition project. In this light, our aim was to investigate the specific needs of adolescent urologic patients, regarding their independence and transition. PATIENTS AND METHODS: 80 patients, born in 1975-1998, with a chronic bladder condition received a questionnaire. They were divided into pre- and post-transfer groups. Parents (n = 7) of post-transfer patients formed a third group. Questionnaires were based on those used in the national transition study, supplemented with urological questions. Pre-transfer patients were asked about their level of independence, what subjects were discussed during consultations, and their expectations and wishes regarding transfer. Post-transfer patients and parents were asked for their opinions on the transfer process. RESULTS: 73% (n = 58) responded (55 pre-transfer and 3 post-transfer patients plus parents). It appeared that the confidence built-up with the pediatric urologist impeded the transfer. An adequate level of disease-related knowledge was reported. Relationships, sexuality and fertility were hardly talked about (respectively n = 17, 16 and 18). Parents played an important role, which patients appreciated, confirming their dependency. Despite the 49% (n = 27) who stated they can arrange their urological care themselves, 44% (n = 24) felt ill-prepared for transfer. CONCLUSION: Although overall self-perceived knowledge is sufficient, the trust in and personal relationship with the pediatric urologist formed the greatest obstruction to successful transition. These findings have been used to improve support during transition by creating a transition protocol.
Subject(s)
Continuity of Patient Care , Needs Assessment , Pediatrics , Spinal Dysraphism/therapy , Urinary Bladder Diseases/therapy , Urology , Adolescent , Chronic Disease , Female , Humans , Male , Parents/psychology , Physician-Patient Relations , Sexuality/psychology , Spinal Dysraphism/complications , Spinal Dysraphism/psychology , Surveys and Questionnaires , Urinary Bladder Diseases/etiology , Urinary Bladder Diseases/psychology , Young AdultABSTRACT
The Missouri River sturgeon iridovirus (MRSIV) is an important factor contributing to losses during the hatchery rearing of juvenile pallid Scaphirhynchus albus and shovelnose S. platorynchus sturgeon. As the virus has not been isolated in cell culture, current detection procedures rely upon a combination of light and electron microscopy. Detection of characteristic virus-infected cells in the integument, usually of the fins, in hematoxylin and eosin (H&E)-stained tissue sections provides a presumptive finding. Confirmation requires observation by electron microscopy of characteristic doubly enveloped hexagonal virions of the appropriate size in the host cell cytoplasm. To improve these diagnostic procedures, a conventional polymerase chain reduction (PCR) assay was developed as a sensitive and specific method for detection of MRSIV DNA as found in numerous tissues of both naturally and experimentally infected pallid and shovelnose sturgeon. Sequences of amplicons obtained from testing of wild-caught shovelnose sturgeon and juvenile pallid sturgeon during hatchery outbreaks were identical, suggesting that the viruses found in both sturgeon are similar or closely related. In addition, a TaqMan PCR was developed that allowed estimates of the concentrations of MRSIV DNA present in the tissues of pallid and shovelnose sturgeon during acute and persistent infection. These new PCR assays are improved methods to detect MRSIV, but equally importantly, they provide insights into to the biology of the agent for more effective management of viral diseases in captive and wild Missouri River sturgeon populations.
Subject(s)
DNA Virus Infections/veterinary , Fish Diseases/virology , Iridovirus/isolation & purification , Animals , Cloning, Molecular , DNA Virus Infections/epidemiology , DNA Virus Infections/virology , DNA, Viral/genetics , Ecosystem , Fish Diseases/epidemiology , Fishes , Genome, Viral , RiversABSTRACT
The prognostic implications of capsular incision (CI) remain to be defined. We evaluated the impact of CI on biochemical recurrence (BCR) and the potential risk factors of CI. Between June 1995 and July 2007, 266 patients with follow-up for at least 6 months, who had neither the seminal vesicle nor lymph node involvement on prostatectomy specimen, were included. Patients with insufficient biopsy data and those with neoadjuvant and/or adjuvant therapy were excluded. CI was defined as tumor extending into the inked margins, at sites except the apex of the prostate, without documented extraprostatic extension (EPE). There were 186 with organ-confined disease and negative surgical margins (pT2/SM-), 12 with organ-confined disease and an apex-only positive margin (pT2/AM+), 35 with CI, 19 with EPE and negative surgical margins (pT3a/SM-) and 13 with EPE and positive surgical margins (pT3a/SM+). We compared BCR-free probability among these five groups and the risk factors for CI were assessed. The 3-year BCR-free probability for each group was 92.7% for pT2/SM-, 75.8% for pT2/AM+, 70.7% with CI, 84% with pT3/SM- and 51% in pT3/SM+. That for CI was worse than pT2/SM- (P=0.007), not significantly different from pT2/AM+ and pT3/SM- (P=0.614, P=0.318, respectively), but better than pT3/SM+ (P=0.044), adjusting for the pre-operative prostate-specific antigen and pathological Gleason score. The risk for CI was significantly associated with more than 25% positive biopsy cores. CI seems to affect BCR and is more likely to occur in proportion to positive biopsy cores.
Subject(s)
Neoplasm Recurrence, Local/pathology , Prostate/pathology , Prostatectomy/adverse effects , Prostatic Neoplasms/pathology , Biopsy, Needle , Humans , Male , Prognosis , Prostate/diagnostic imaging , Prostate/surgery , Prostatectomy/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , UltrasonographyABSTRACT
BACKGROUND: An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw. METHODS: Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague-Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), or SOD (4000 U/kg)+L-NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats. RESULTS: Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and L-NAME, which were used to investigate the roles of superoxide (O2(-)) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks. CONCLUSIONS: Our findings suggest that O2(-) and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects.
Subject(s)
Ischemia/complications , Reactive Oxygen Species/metabolism , Allopurinol/pharmacology , Animals , Chronic Disease , Cold Temperature , Enzyme Inhibitors/pharmacology , Free Radical Scavengers/pharmacology , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , Pain/etiology , Pain/metabolism , Physical Stimulation , Rats , Rats, Sprague-Dawley , Reperfusion Injury/complications , Superoxide Dismutase/antagonists & inhibitors , Xanthine Oxidase/antagonists & inhibitorsABSTRACT
Phosphatidylinositol 3-kinase (PI3K) signalling plays a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation, and tumourigenesis. PI3K is overexpressed in many human cancers, including endometrial carcinomas, one of the most common female genital tract malignancies. Here, we used small interfering RNA (siRNA) targeted to PI3K p110-beta to determine whether inhibition of the beta isoform could be a potential therapeutic target for endometrial carcinoma. In this study, treatment of HEC-1B endometrial cancer cells with PI3K p110-beta-specific siRNA resulted in increased apoptosis and decreased tumour cell proliferation. Depletion of PI3K p110-beta decreased the protein levels of AKT1, AKT2, pAKT, and mTOR-downstream targets of PI3K. Knock-down of PI3K p110-beta by siRNA also induced decreased expression of cyclin E and Bcl-2, suggesting that PI3K p110-beta stimulates tumour growth, at least in part by regulating cyclin E and Bcl-2. Thus, our results indicate that siRNA-mediated gene silencing of PI3K p110-beta may be a useful therapeutic strategy for endometrial cancers overexpressing PI3K p110-beta.
Subject(s)
Apoptosis/genetics , Endometrial Neoplasms/physiopathology , Phosphatidylinositol 3-Kinases/genetics , RNA Interference/physiology , RNA, Small Interfering/genetics , Cell Cycle/genetics , Cell Division/genetics , Cell Line, Tumor , Class I Phosphatidylinositol 3-Kinases , Endometrial Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Gene Silencing/physiology , Humans , Isoenzymes/genetics , Neoplasm Proteins/analysis , Phosphatidylinositol 3-Kinases/analysis , Protein Kinases/analysis , Proto-Oncogene Proteins c-akt/analysis , RNA, Neoplasm/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , TOR Serine-Threonine KinasesABSTRACT
BACKGROUNDS AND OBJECTIVE: There is a high incidence of pain following intravenous injection of propofol, and many studies have been conducted to find a way of reducing this. The administration of lidocaine and, recently, remifentanil has also been used for this purpose, but it is only partially effective. Thus, the purpose of this study was to investigate the analgesic effect of a combination of pretreatment with remifentanil and premixture of lidocaine with propofol and to compare either treatment alone during propofol injection in dorsal hand-veins. METHODS: In a prospective, randomized, double-blinded trial, we studied 141 adult patients scheduled for elective surgery. The combination of pretreatment of remifentanil (0.35 microg kg(-1) min(-1)) and a premixture of lidocaine with propofol (mixture of propofol 1% and lidocaine 1% in a 10:1 ratio) was compared with either treatment alone in the prevention of pain on propofol injection. Pain was assessed on a four-point scale (0=none, 1=mild, 2=moderate, 3=severe) during propofol injection. Patients in Group B received remifentanil (0.35 microg kg(-1) min(-1)) 30 s before the injection of propofol. RESULTS: The reduction of pain on propofol injection was similar in both the remifentanil pretreatment and lidocaine premixture groups (62.2% vs. 62.2%). Combination therapy was associated with a higher incidence of patients without pain (91.3%) than either treatment alone (P<0.001). On analysing the injection pain scores, we found a significant reduction of the score in the remifentanil and lidocaine Group C compared with the lidocaine Group A (P<0.001) and the remifentanil Group B (P<0.001). CONCLUSIONS: The combination of pretreatment of remifentanil and premixture of lidocaine with propofol was more effective in reducing the incidence of pain on injection of propofol than either treatment alone.
Subject(s)
Anesthetics, Intravenous/adverse effects , Pain/drug therapy , Propofol/adverse effects , Adult , Analysis of Variance , Anesthetics, Intravenous/administration & dosage , Anesthetics, Local/therapeutic use , Double-Blind Method , Drug Combinations , Female , Humans , Injections, Intravenous/adverse effects , Lidocaine/therapeutic use , Male , Middle Aged , Pain/etiology , Pain Measurement/methods , Piperidines/therapeutic use , Propofol/administration & dosage , Prospective Studies , Remifentanil , Treatment OutcomeABSTRACT
Adrenal medullary chromaffin cells secrete several neuroactive substances including catecholamines and opioid peptides that produce analgesic effects in the central nervous system. This study was designed to investigate whether intrathecal microencapsulated chromaffin cells could release analgesic materials producing antiallodynic effects on the chronic neuropathic pain in rats induced by chronic constriction injury (CCI) of the sciatic nerve. Prior to intrathecal implantation, chromaffin cells were encapsulated with alginate and poly-L-lysine to protect them from the host immune system. Behavior tests were performed before CCI, 1 week later, and at 4, 7, 14, 21, 28 days postimplantation. At the end of study, we performed cerebrospinal fluid (CSF) collection and implant retrieval. We observed that intrathecal implantation of encapsulated xenogenic chromaffin cells reduced the mechanical and cold allodynia in a model of neuropathic pain. CSF levels of catecholamines and metenkephalin in the rats that received implants were higher than the controls. In addition, we observed chronic survival of implants. These results suggested that intrathecal microencapsulated chromaffin cells may represent a new approach to chronic neuropathic pain management.
Subject(s)
Analgesics/administration & dosage , Chromaffin Cells/transplantation , Absorbable Implants , Animals , Cattle , Cell Survival , Chromaffin Cells/cytology , Chromaffin Cells/pathology , Rats , Sciatic Nerve , Spine , Transplantation, HeterologousABSTRACT
Adhesive interaction between a tip and a sample surface was examined on a microscopic scale by pulsed-force-mode atomic force microscopy (PFM-AFM). The signal measured by monitoring pull-off force is influenced by various factors such as topography, elasticity, electrostatic charges, and adsorbed water on surfaces. Here, we focus on the topographic effects on the adhesive interaction. To clarify the topographic influence, the adhesive force measurement of a stretched DNA molecule with a smaller radius of curvature than that of a tip was carried out at low relative humidity (RH) with an alkanethiol-modified tip. The experimental conditions such as low RH and the use of the alkanethiol-modified tip were required to minimise the influence of water capillary force on hydrated DNA strands. The hydrophobic modification of a substrate surface was also important to minimise the adsorbed water effect. The DNA molecules were stretched on the substrate surfaces by an immobilisation process called a dynamic molecular combing method. The two-component vapour-phase surface modification with an alkylsilane mixed with a silane derivative containing an amino end group enhanced the DNA adsorption due to the electrostatic interaction. The experimental results for the topographic effects on the adhesive force mapping were reproducible.
Subject(s)
DNA/chemistry , Microscopy, Atomic Force/methods , AdhesivenessABSTRACT
We demonstrate here by imaging successive surface reactions in self-assembled monolayers (SAMs) on Au(111) at molecular scale with a scanning tunneling microscope (STM): (i) SAM matrices formation with 1-octanethiol on Au(111) in ethanol, (ii) insertion of N-Fmoc-aminooctanethiol into the SAM matrices in ethanol, and (iii) removal of the Fmoc protecting group with tris(2-aminoethyl)amine (TAEA). The total reaction is formation of SAMs containing a small amount of NH2 terminated molecules in the CH3 terminated SAM matrices. After the reaction of the protecting group with TAEA, STM imaging revealed the decrease in heights of the inserted molecules on average. We attributed this observation to removal of the protecting group by taking account of a convolution of electronic and topographic contributions to observed STM heights. Apparent areas of the terminal groups, however, became larger on removal. The increase in the areas was attributed to water adsorption to the NH2 terminal group under air.
ABSTRACT
The effect of a surface water layer on DNA strands deposited on a substrate was studied by atomic force microscopy (AFM). DNA molecules were deposited and stretched on chemically modified glass coverslips by a molecular combing method. Lambda bacteriophage DNA molecules were aligned on the organosilane-modified substrate surfaces by chemical and physical adsorption during the molecular combing. The combed DNA molecules were observed in humidity-controlled air and in aqueous solutions by pulsed-force-mode AFM (PFM-AFM). Chemical modification of cantilevers with an Au-coated tip by organothiol compounds was also applied to DNA observation. Mapping adhesive forces in aqueous media was useful to discriminate chemically the DNA strands from the substrate surface. The results suggest that PFM-AFM can be used widely to image the stretched DNA molecules on the silane-modified substrates.