In Addition (in + addition)

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Distribution within Medical Sciences

Kinds of In Addition

  • conclusion in addition
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  • ms. in addition
  • ph. in addition
  • v. in addition

  • Selected Abstracts

    Decision Factors and the Recognition of Medical Specialty in Patients Receiving Cosmetic Laser and Intense Pulsed Light Treatment

    BACKGROUND In addition to dermatologists and plastic surgeons, physicians of other medical specialties also provide cosmetic laser and light treatment. OBJECTIVE This study aimed to determine the major decision factors in patients who received cosmetic laser or intense pulsed light treatment and how they perceived different medical specialties in providing such services. METHODS The method of factor analysis was adopted to extract the common characteristics (major decision factors) from a list of 17 items patients would regard as important when they planned to receive laser and intense pulsed light treatment. In addition, the level of recognition of different medical specialties in cosmetic patients was indirectly forecast using an analytic hierarchy process. RESULTS Medical competence (0.3296) was the most important decision factor, followed by recommendation (0.2198), friendliness (0.1350), cost (0.1307), complete service (0.0984), and the physical attributes of the physician (0.0865). Dermatologists and plastic surgeons outscored cosmetic practitioners in five factors except for cost, in which the plastic surgeons were weakest. CONCLUSION Medical competence and recommendation are the core issues for cosmetic patients. Dermatologists and plastic surgeons gain better overall recognition than physicians of other medical specialties in cosmetic patients. [source]

    Periungual Basal Cell Carcinoma: Case Report and Literature Review

    BACKGROUND Basal cell carcinoma, the most common malignancy in humans, rarely occurs on the nail unit and may be frequently misdiagnosed clinically. OBJECTIVES To present a case of basal cell carcinoma of the nail unit successfully treated with the mohs technique and to review the literature regarding this unique presentation of this tumor. MATERIALS AND METHODS: Case report and review of the English literature of nail unit basal cell carcinoma. RESULTS In addition to the currently described patient, 17 other patients with nail unit basal cell carcinaoma have been reported. The tumor occurred approximately 3 times more often on the fingers then on the toes and had a slight predilection to occur in men. Ulceration, noted in more than one-half of patients, was the most common presentation of nail unit basal cell carcinoma. Mohs micrographic surgery. Often with second intention healing, was successfully employed in 39% of patients. CONCLUSIONS Basal cell carcinaom infrequently involves the nail unit and often presents as ulceration. Adequate biopsy of the lesion is essential in making a timely diagnosis. Mohs micrographic surgery with second intension healing is an effective treatment that may offer excellent cosmetic and functional results. [source]

    ROCK inhibitor (Y27632) increases apoptosis and disrupts the actin cortical mat in embryonic avian corneal epithelium

    Kathy K.H. Svoboda
    Abstract The embryonic chicken corneal epithelium is a unique tissue that has been used as an in vitro epithelial sheet organ culture model for over 30 years (Hay and Revel [1969] Fine structure of the developing Avian cornea. Basel, Switzerland: S. Karger A.G.). This tissue was used to establish that epithelial cells could produce extracellular matrix (ECM) proteins such as collagen and proteoglycans (Dodson and Hay [1971] Exp Cell Res 65:215,220; Meier and Hay [1973] Dev Biol 35:318,331; Linsenmayer et al. [1977] Proc Natl Acad Sci U S A 74:39,43; Hendrix et al. [1982] Invest Ophthalmol Vis Sci 22:359,375). This historic model was also used to establish that ECM proteins could stimulate actin reorganization and increase collagen synthesis (Sugrue and Hay [1981] J Cell Biol 91:45,54; Sugrue and Hay [1982] Dev Biol 92:97,106; Sugrue and Hay [1986] J Cell Biol 102:1907,1916). Our laboratory has used the model to establish the signal transduction pathways involved in ECM-stimulated actin reorganization (Svoboda et al. [1999] Anat Rec 254:348,359; Chu et al. [2000] Invest Ophthalmol Vis Sci 41:3374,3382; Reenstra et al. [2002] Invest Ophthalmol Vis Sci 43:3181,3189). The goal of the current study was to investigate the role of ECM in epithelial cell survival and the role of Rho-associated kinase (p160 ROCK, ROCK-1, ROCK-2, referred to as ROCK), in ECM and lysophosphatidic acid (LPA) -mediated actin reorganization. Whole sheets of avian embryonic corneal epithelium were cultured in the presence of the ROCK inhibitor, Y27632 at 0, 0.03, 0.3, 3, or 10 ,M before stimulating the cells with either collagen (COL) or LPA. Apoptosis was assessed by Caspase-3 activity assays and visualized with annexin V binding. The ROCK inhibitor blocked actin cortical mat reformation and disrupted the basal cell lateral membranes in a dose-dependent manner and increased the apoptosis marker annexin V. In addition, an in vitro caspase-3 activity assay was used to determine that caspase-3 activity was higher in epithelia treated with 10 ,M Y-27632 than in those isolated without the basal lamina or epithelia stimulated with fibronectin, COL, or LPA. In conclusion, ECM molecules decreased apoptosis markers and inhibiting the ROCK pathway blocked ECM stimulated actin cortical mat reformation and increased apoptosis in embryonic corneal epithelial cells. Developmental Dynamics 229:579,590, 2004. © 2004 Wiley-Liss, Inc. [source]

    Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance,

    DIABETIC MEDICINE, Issue 10 2008
    M. Toshihiro
    Abstract Aims, We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress. Methods, The participants were 128 male Japanese company employees (mean age, 49.3 ± 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan,Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social,psychological factors. Results, Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow-up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1,6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white-collar worker (HR = 0.34, P = 0.033), non-smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042). Conclusions, In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white-collar worker, a non-smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT. [source]

    Left Ventricular Function in Male Patients with Secondary Hypogonadism

    ECHOCARDIOGRAPHY, Issue 3 2007
    Oben Baysan M.D.
    Background: In addition to the effects on ventricular repolarization, testosterone could also affect left ventricular performance. The enhancement of left ventricular contractility in testosterone-deficient rats following testosterone replacement implies to the possible testosterone effect. Objectives: The aim of the current study is to reveal the alterations of left ventricular functions, if any, in secondary hypogonadal male patients. Methods: Thirty-four males with secondary hypogonadism comprised the study group. The control group consisted of 30 healthy subjects. Echocardiographic measurements including left ventricular dimensions, ejection fraction, mitral inflow, and left ventricular outflow parameters were obtained from all subjects. Tissue Doppler parameters were also measured from left ventricular lateral wall and interventricular septum. Results: Left ventricular diameters, wall thicknesses, and performance parameters were similar in both groups. Mitral inflow parameters showed a statistically insignificant difference. Pulse-wave tissue Doppler interpretation of hypogonadal and healthy subjects were similar in terms of lateral and septal basal segment Sm, Em, and Am wave velocities. Conclusions: Regarding the findings of previous studies that showed impaired myocardial contractility and lusitropy in testosterone deficient rats and our study results, further studies are needed for better understanding of testosterone's effects on human myocardium. [source]

    New structures of vector control systems for permanent magnet synchronous motors with core loss

    Shinji Shinnaka
    Abstract This paper investigates and proposes new system structures for vector control of permanent-magnet synchronous motors (PMSMs) with core loss. The proposed vector control systems have the following versatile features. (a) The systems employ the structures allowing control of the stator current through control of the load current. (b) The systems employ unique "stator voltage feedback-use" structures in order to accomplish simply the load current control. (c) The produced torque is directly related to the load current, and the precise torque control can be attained through the load current control. (d) The relation between produced torque and the load current is nonlinear for salient-pole PMSMs similar to the case of no core loss, and a variety of the load current commands can be selected from viewpoints of minimum loss and/or wide speed range drives. The system structures add no constraint to the selection of the load current commands. (e) In addition to the torque control, the speed control can be allowed, where linearity between output of the speed controller and produced torque is kept. The validity of versatile features is verified through the numerical experiments. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 170(3): 28,39, 2010; Published online in Wiley InterScience (www.interscience. DOI 10.1002/eej.20910 [source]

    Development of an oxide semiconductor thick film gas sensor for the detection of total volatile organic compounds

    Masahiro Kadosaki
    Abstract Since the amendment of the Building Standards Law in 2003, the installation of ventilators is compulsory in newly built houses, because many persons suffer from indoor air pollution caused by volatile organic compounds (VOCs). The goal of this research is to develop a gas sensor that can monitor the total VOC (TVOC) gases indoors and then to control the ventilator efficiently using the sensor. In order to develop a sensor that detects TVOC, the responses of four oxide semiconductor materials to 37 different VOC gases were studied. These materials showed small responses to halogenated and aliphatic hydrocarbon gases. As a result of improving the response to these gases, among four metal oxides examined, SnO2 and WO3 showed high sensitivities by the addition of Pd and Pt. The sensing properties of SnO2 for halogenated hydrocarbon gases were greatly improved by the addition of 0.5 wt% Pd. The sensing properties of SnO2 for aliphatic hydrocarbon gases were improved by the addition of 0.7 wt% Pt. In addition, a sensor element with the addition of both platinum and palladium, that is, Pt (0.5 wt%)-Pd (0.5 wt%)-SnO2, showed a large response to many of the VOC gases examined. © 2010 Wiley Periodicals, Inc. Electron Comm Jpn, 93(10): 34,41, 2010; Published online in Wiley Online Library ( DOI 10.1002/ecj.10190 [source]

    Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism

    ADDICTION, Issue 4 2009
    Dirk W. Lachenmeier
    ABSTRACT Aims In addition to being produced in ethanol metabolism, acetaldehyde occurs naturally in alcoholic beverages. Limited epidemiological evidence points to acetaldehyde as an independent risk factor for cancer during alcohol consumption, in addition to the effects of ethanol. This study aims to estimate human exposure to acetaldehyde from alcoholic beverages and provide a quantitative risk assessment. Methods The human dietary intake of acetaldehyde via alcoholic beverages was estimated based on World Health Organization (WHO) consumption data and literature on the acetaldehyde contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the European Food Safety Authority's margin of exposure (MOE) approach with benchmark doses obtained from dose,response modelling of animal experiments. Life-time cancer risk was calculated using the T25 dose descriptor. Results The average exposure to acetaldehyde from alcoholic beverages was estimated at 0.112 mg/kg body weight/day. The MOE was calculated to be 498, and the life-time cancer risk at 7.6 in 10 000. Higher risk may exist for people exposed to high acetaldehyde contaminations, as we have found in certain unrecorded alcohol beverages in Guatemala and Russia, for which we have demonstrated possible exposure scenarios, with risks in the range of 1 in 1000. Conclusions The life-time cancer risks for acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment set between 1 : 10 000 and 1 : 1 000 000. Alcohol consumption has thus been identified as a direct source of acetaldehyde exposure, which in conjunction with other sources (food flavourings, tobacco) results in a magnitude of risk requiring intervention. An initial public health measure could be to reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive. [source]

    Microbial community structure of ethanol type fermentation in bio-hydrogen production

    Nanqi Ren
    Summary Three continuous stirred-tank reactors (CSTRs) were used for H2 production from molasses wastewater at influent pH of 6.0,6.5 (reactor A), 5.5,6.0 (reactor B), or 4.0,4.5 (reactor C). After operation for 28 days, the microbial community formed ethanol type (C), propionate type (A) and ethanol-butyrate-mixed type (B) fermentation. The H2 production rate was the highest for ethanol type fermentation, 0.40 l (g VSS),1 day,1 or 0.45 l H2 (g COD removed),1. Microbial community dynamics and diversity were analysed using double-gradient denaturing gradient gel electrophoresis (DG-DGGE). Denaturing gradient gel electrophoresis profiles indicated that the community structures changed quickly in the first 14 days. Phylogenetic analysis indicated that the dominant bacterial groups were low G+C Gram-positive bacteria, Bacteroides, ,-Proteobacteria and Actinobacteria; ,-Proteobacteria, ,-Proteobacteria, ,-Proteobacteria and Spirochaetes were also presented as minor groups in the three reactors. H2 -producing bacteria were affiliated with Ethanoligenens, Acetanaerobacterium, Clostridium, Megasphaera, Citrobacter and Bacteroides. An ethanol-based H2 -producing bacterium, Ethanoligenens harbinense CGMCC1152, was isolated from reactor C and visualized using fluorescence in situ hybridization (FISH) to be 19% of the eubacteria in reactor C. In addition, isoenzyme activity staining for alcohol dehydrogenase (ADH) supported that the majority of ethanol-producing bacteria were affiliated with Ethanoligenens in the microbial community. [source]

    Cadmium induced oxidative stress influence on glutathione metabolic genes of Camellia sinensis (L.) O. Kuntze

    Prashant Mohanpuria
    Abstract Glutathione, a tripeptide with sulfhydryl (-SH) group is a very crucial compound primarily involved in redox balance maintenance of the cellular environment. In this study, we monitored the influence of Cd exposure on the transcript levels of glutathione metabolic genes in bud tissues, the youngest leaf, of Camellia sinensis L. In addition, some physiochemical parameters were also studied. Cd exposure decreased chlorophyll and protein contents, while increase was observed in lipid peroxidation upon Cd treatments. These changes were found to be concentration and duration dependent, indicating the occurrence of oxidative stress upon Cd exposure. The transcript levels of glutathione biosynthetic genes viz. ,-glutamylcysteine synthetase (,-ECS) and glutathione synthetase (GSHS) increased upon Cd exposure. Furthermore, transcript levels of glutathione reductase (GR), an enzyme involved in reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH), also showed upregulation on Cd exposure. However, the transcript levels of glutathione-S-transferase (GST), an enzyme involved in forming metal,GSH complex and help in sequestration of high levels of metal ions to vacuole, did not show any change on Cd treatment. This study document that Cd exposure induces oxidative stress in Camellia sinensis and the upregulation in transcript levels of glutathione metabolic genes except GST have suggested the role of these enzymes in the protection of plants from high level Cd exposure. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 368,374, 2007. [source]

    General practitioners' and family physicians' negative beliefs and attitudes towards discussing smoking cessation with patients: a systematic review

    ADDICTION, Issue 10 2005
    Florian Vogt
    ABSTRACT Objective, To estimate the proportion of general practitioners (GPs) and family physicians (FPs) with negative beliefs and attitudes towards discussing smoking cessation with patients. Methods A systematic review. Study selection All studies published in English, in peer-reviewed journals, which allowed the extraction of the proportion of GPs and FPs with negative beliefs and attitudes towards discussing smoking cessation. Data synthesis Negative beliefs and attitudes were extracted and categorised. Proportions were synthesized giving greater weight to those obtained from studies with larger samples. Those assessed in two or more studies are reported. Results Across 19 studies, eight negative beliefs and attitudes were identified. While the majority of GPs and FPs do not have negative beliefs and attitudes towards discussing smoking with their patients, a sizeable minority do. The most common negative beliefs were that such discussions were too time-consuming (weighted proportion: 42%) and were ineffective (38%). Just over a quarter (22%) of physicians reported lacking confidence in their ability to discuss smoking with their patients, 18% felt such discussions were unpleasant, 16% lacked confidence in their knowledge, and relatively few considered discussing smoking outside of their professional duty (5%), or that this intruded upon patients' privacy (5%), or that such discussion were inappropriate (3%). Conclusions In addition to providing skills training, interventions designed to increase the implementation of smoking cessation interventions by primary care physicians may be more effective if they address a range of commonly held negative beliefs and attitudes towards discussing smoking cessation. These include beliefs and values that influence primary care physicians' judgements about whether discussing smoking is an effective use of their time. [source]

    Pharmacokinetics of Levetiracetam and Its Enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide in Dogs

    EPILEPSIA, Issue 7 2001
    Nina Isoherranen
    Summary: ,Purpose: The new antiepileptic drug, levetiracetam (LEV, ucb LO59), is a chiral molecule with one asymmetric carbon atom whose anticonvulsant activity is highly enantioselective. The purpose of this study was to evaluate and compare the pharmacokinetics (PK) of LEV [(S)-,-ethyl-2-oxo-pyrrolidine acetamide] and its enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide (REV) after i.v. administration to dogs. This is the first time that the pharmacokinetics of both enantiomers has been evaluated. Methods: Optically pure LEV and REV were synthesized, and 20 mg/kg of individual enantiomers was administered intravenously to six dogs. Plasma and urine samples were collected until 24 h, and the concentrations of LEV and REV were determined by an enantioselective assay. The levels of 2-pyrrolidone- N -butyric acid, an acid metabolite of LEV and REV, were determined by high-performance liquid chromatography (HPLC). The data were used for PK analysis of LEV and REV. Results: LEV and REV had similar mean ± SD values for clearance; 1.5 ± 0.3 ml/min/kg and volume of distribution; 0.5 ± 0.1 L/kg. The half-life (t1/2) and mean residence time (MRT) of REV (t1/2, 4.3 ± 0.8 h, and MRT, 6.0 ± 1.1 h) were, however, significantly longer than those of LEV (t1/2, 3.6 ± 0.8 h, and MRT, 5.0 ± 1.2 h). The renal clearance and fraction excreted unchanged for LEV and REV were significantly different. Conclusions: In addition to the enantioselective pharmacodynamics, ,-ethyl-2-oxo-pyrrolidine acetamide has enantioselective PK. The enantioselectivity was observed in renal clearance. Because REV has more favorable PK in dogs than LEV, the higher antiepileptic potency of LEV is more likely due to intrinsic pharmacodynamic activity rather than to enantioselective PK. [source]

    Alcohol abuse in a metropolitan city in China: a study of the prevalence and risk factors

    ADDICTION, Issue 9 2004
    Zhang Jiafang
    ABSTRACT Aims To investigate the prevalence of alcohol abuse in modern China and to explore the risk factors that may be associated with alcohol abuse. Design A face-to-face interview was carried out in a random sample with 2327 respondents. Setting Respondents were selected randomly from Wuhan City, Hubei Province, China, between May and June 2002. Participants Fifteen,65-year-old urban Chinese adults. Measurements Scores for alcohol abuse and related risk factors were the main measures. Findings (1) Nearly 15% of urban Chinese adults aged 15,65 were alcohol abusers. (2) Deviant drinking habits of mother, schoolmates, colleagues or friends all had a negative impact on the respondent's alcohol drinking behaviours, and higher economic status, current smokers, being male and being older were identified as risk factors related to alcohol abuse. In particular, if a drinker's mother used alcohol frequently then this drinker was more likely to become an alcohol abuser than those drinkers whose mothers did not use alcohol frequently (P = 0.0001). Fathers' drinking behaviours do not have a significant impact on the alcohol abusers. Conclusions In addition to common risk factors such as economic status, deviant peers' and fellows' drinking behaviours and negative attitudes to alcohol drinking, maternal alcohol drinking habit influenced significantly the offspring's drinking habits. Therefore, efficient intervention and education of healthy drinking habits in early motherhood is necessary for Chinese women. [source]

    Clinical dental examinations of 357 donkeys in the UK.

    Part 2: Epidemiological studies on the potential relationships between different dental disorders, between dental disease, systemic disorders
    Summary Reasons for performing study: Dental disease has been shown to be a risk factor for weight loss and colic in horses. No extensive clinical studies in donkeys have investigated the potential relationship between different dental disorders, or between dental disease and systemic disorders. Objectives: To determine possible associations between dental disease and body condition score, weight loss, the need for supplemental feeding and prevalence of colic in donkeys of all ages, and to gain a better understanding of the pathogenesis of dental disease by the determination of associations between different dental disorders. Methods: A prospective cross-sectional analysis of clinical dental examinations of 357 donkeys in The Donkey Sanctuary, Sidmouth was performed. Other epidemiological factors such as estimated age group, body condition score, weight loss, medical history and supplemental feeding were also recorded, and multiple regression analyses were performed to determine possible associations. Results: Donkeys from older age groups were more likely to have dental disease, poor body condition score and suffered previous colic episodes. The presence of dental disease was also significantly associated with weight loss, colic, low body condition score and the need for supplemental feeding. The presence of diastemata, periodontal disease, wave mouth, smooth mouth and step mouth are frequently associated with the presence of other dental disorders. Conclusions: In addition to oral-related pain, dental disease can cause significant systemic disorders and so has increased welfare implications in donkeys. Some dental disorders promote the development of other types of dental abnormalities and thus increase the severity of dental disease in individual animals. Potential significance: Effective treatment of dental disorders slows down the progression of dental disease and decreases the risk of developing some medical disorders such as colic and weight loss that are associated with dental disease. [source]

    Influence of track surface on the equine superficial digital flexor tendon loading in two horses at high speed trot

    N. Crevier-Denoix
    Summary Reasons for performing study: Although track surfaces are a risk factor of tendon injuries, their effects on tendon loading at high speed are unknown. Using a noninvasive ultrasonic technique, it is now possible to evaluate the forces in the superficial digital flexor tendon (SDFT) in exercise conditions. Objectives: To compare the effects of an all-weather waxed track (W) vs. a crushed sand track (S), on the SDFT loading in the trotter horse at high speed. Methods: Two trotter horses were equipped with the ultrasonic device (1 MHz ultrasonic probe, fixed on the palmar metacarpal area of the right forelimb). For each trial, data acquisition was made at 400 Hz and 10 consecutive strides were analysed. In each session, the 2 track surfaces were tested in a straight line. The speed was imposed at 10 m/s and recorded. The right forelimb was also equipped with a dynamometric horseshoe and skin markers. The horse was filmed with a high-speed camera (600 Hz); all recordings were synchronised. Statistical differences were tested using the GLM procedure (SAS; P<0.05). Results: Maximal tendon force was significantly lower on W compared with S. In addition to maximal force peaks around mid-stance, earlier peaks were observed, more pronounced on S than on W, at about 13%(horse 2) and 30% (both horses) of the stance phase. Comparison with kinematic data revealed that these early peaks were accompanied by plateaux in the fetlock angle-time chart. For high tendon forces, the tendon maximal loading rate was significantly lower on W than on S. Conclusions and potential clinical relevance: The all-weather waxed track appears to induce a lesser and more gradual SDFT loading than crushed sand. The SDFT loading pattern at high speed trot suggests proximal interphalangeal joint movements during limb loading. [source]

    Role of Toll-like receptor 4 in the initiation and progression of atherosclerotic disease

    G. Pasterkamp
    Abstract The family of Toll-like receptors (TLRs) initiates an innate immune response after recognition of pathogen-associated molecular patterns (PAMPs). Evidence is accumulating that TLRs, and particularly TLR4, are important players in the initiation and progression of atherosclerotic disease. Not only exogenous ligands but also endogenous ligands that are expressed during arterial injury are recognized by TLR4. Mouse knockout studies and epidemiological studies of human TLR4 polymorphisms have demonstrated that the TLR4 might play a role in the initiation and progression of atherosclerosis. This review will summarize the latest progression in research on the role of TLR4 in arterial occlusive disease In addition, the potential of intervention in TLR4 signalling to influence progression of atherosclerotic disease is discussed. [source]

    Impaired cardiovagal and vasomotor responses to baroreceptor stimulation in type II diabetes mellitus

    E. O. Sanya
    Abstract Background In diabetic patients, impairment of the cardiovagal limb of the baroreflex has been well established. However, the role of sympathetic mediated baroreflex vasomotor control of the blood vessels is not well defined. We therefore assessed the vasomotor responses to sinusoidal baroreceptor stimulation in diabetic patients. Materials and methods We studied 14 type II diabetic patients (age; 57 ± 7 years) and 18 healthy controls (age; 59 ± 11 years). Oscillatory neck suction was applied at 0·1 Hz to assess the sympathetic modulation of the heart and blood vessels, and at 0·2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was paced at 0·25 Hz. Spectral analysis was used to evaluate the oscillatory responses of RR-interval and blood pressure. Results The diabetic patients showed a significantly lower RR-interval response (P < 0·05) to the 0·1 Hz neck suction (2·52 ± 0·50,3·62 ± 0·54 ln ms2) than the controls (4·23 ± 0·31,6·74 ± 0·36 ln ms2). The increase in power of 0·1 Hz systolic blood pressure oscillations during 0·1 Hz suction was also significantly smaller (P < 0·05) in the diabetics (1·17 ± 0·44,1·69 ± 0·44 mmHg2) than in the controls (1·60 ± 0·29 mmHg2,5·87 ± 1·25 mmHg2). The magnitude of the peak of the 0·2 Hz oscillation in the RR-interval in response to 0·2 Hz neck stimulation was significantly greater (P < 0·05) in the controls (3·42 ± 0·46 ln ms2) than in the diabetics (1·58 ± 0·44 ln ms2). Conclusion In addition to cardiovagal dysfunction, baroreflex-mediated sympathetic modulation of the blood vessels is impaired in type II diabetic patients. [source]

    CLINICAL STUDY: Attentional bias in alcohol-dependent patients: the role of chronicity and executive functioning

    ADDICTION BIOLOGY, Issue 2 2009
    Sabine Loeber
    ABSTRACT It has been suggested that the attention towards alcohol-related stimuli increases with the duration of drinking and alcohol dependence. The present study aimed to assess whether an attentional bias was present in detoxified alcohol-dependent patients, and if the magnitude of the attentional bias depended on the subject's drinking history and variables of executive functioning. Attentional bias was assessed in 30 alcohol-dependent patients using a visual dot-probe task with a picture presentation time of 50 ms. In addition, patients completed a variety of different cognitive tasks such as attention, continuous performance, working memory, set shifting and inhibitory control tests. Based on correlation analysis we split the patient sample on the median with regard to the duration of alcohol dependence and our results indicated a significant attentional bias towards alcohol-associated pictures in patients dependent for less than 9 years, but not in patients with a longer duration of dependence. The two patient samples differed significantly with regard to attention and working memory functioning with patients who were dependent for more than 9 years showing a greater impairment. When impairment of attention and working memory were controlled for, the group differences in attentional bias were no longer significant. Our results indicate that differences with regard to drinking-related variables as well as cognitive functioning seem to modulate attentional bias and need to be taken into account in models of drinking maintenance. [source]

    EFNS guidelines on the use of neuroimaging in the management of multiple sclerosis

    M. Filippi
    Magnetic resonance (MR)-based techniques are widely used for the assessment of patients with suspected and definite multiple sclerosis (MS). However, despite the publication of several position papers, which attempted to define the utility of MR techniques in the management of MS, their application in everyday clinical practice is still suboptimal. This is probably related, not only, to the fact that the majority of published guidelines focused on the optimization of MR technology in clinical trials, but also to the continuing development of modern, quantitative MR-based techniques, that have not as yet entered the clinical arena. The present report summarizes the conclusions of the ,EFNS Expert Panel of Neuroimaging of MS' on the application of conventional and non-conventional MR techniques to the clinical management of patients with MS. These guidelines are intended to assist in the use of conventional MRI for the diagnosis and longitudinal monitoring of patients with MS. In addition, they should provide a foundation for the development of more widespread but rational clinical applications of non-conventional MR-based techniques in studies of MS patients. [source]

    The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory-related activity of hypoglossal motoneurons in the adult rat

    Fernando Montero
    Abstract Motoneurons integrate interneuronal activity into commands for skeletal muscle contraction and relaxation to perform motor actions. Hypoglossal motoneurons (HMNs) are involved in essential motor functions such as breathing, mastication, swallowing and phonation. We have investigated the role of the gaseous molecule nitric oxide (NO) in the regulation of the inspiratory-related activity of HMNs in order to further understand how neural activity is transformed into motor activity. In adult rats, we observed nitrergic fibers and bouton-like structures in close proximity to motoneurons, which normally lack the molecular machinery to synthesize NO. In addition, immunohistochemistry studies demonstrated that perfusion of animals with a NO donor resulted in an increase in the levels of cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP pathway were micro-iontophoretically applied while performing single-unit extracellular recordings in the adult decerebrated rat. Application of a NO synthase inhibitor or a sGC inhibitor induced a statistically significant reduction in the inspiratory-related activity of HMNs. However, excitatory effects were observed by ejection of a NO donor or a cell-permeable analogue of cGMP. In slice preparations, application to the bath of a NO donor evoked membrane depolarization and a decrease in rheobase, which were prevented by co-addition to the bath of a sGC inhibitor. These effects were not prevented by reduction of the spontaneous synaptic activity. We conclude that NO from afferent fibers anterogradely modulates the inspiratory-related activity of HMNs by a cGMP-dependent mechanism in physiological conditions. [source]

    Inactivation of colicin Y by intramembrane helix,helix interaction with its immunity protein

    FEBS JOURNAL, Issue 21 2008
    David, majs
    The construction of hybrids between colicins U and Y and the mutagenesis of the colicin Y gene (cya) have revealed amino acid residues important for interactions between colicin Y and its cognate immunity protein (Cyi). Four such residues (I578, T582, Y586 and V590) were found in helices 8 and 9 of the colicin Y pore-forming domain. To verify the importance of these residues, the corresponding amino acids in the colicin B protein were mutated to the residues present in colicin Y. An Escherichia coli strain with cloned colicin Y immunity gene (cyi) inactivated this mutant, but not the wild-type colicin B. In addition, interacting amino acid pairs in Cya and Cyi were identified using a set of Cyi point mutant strains. These data are consistent with antiparallel helix,helix interactions between Cyi helix T3 and Cya helix 8 of the pore-forming domain as a molecular mechanism of colicin Y inactivation by its immunity protein. [source]

    The relationship between thermal stability and pH optimum studied with wild-type and mutant Trichoderma reesei cellobiohydrolase Cel7A

    FEBS JOURNAL, Issue 5 2003
    Harry Boer
    The major cellulase secreted by the filamentous fungus Trichoderma reesei is cellobiohydrolase Cel7A. Its three-dimensional structure has been solved and various mutant enzymes produced. In order to study the potential use of T. reesei Cel7A in the alkaline pH range, the thermal stability of Cel7A was studied as a function of pH with the wild-type and two mutant enzymes using different spectroscopic methods. Tryptophan fluorescence and CD measurements of the wild-type enzyme show an optimal thermostability between pH 3.5,5.6 (Tm, 62 ± 2 °C), at which the highest enzymatic activity is also observed, and a gradual decrease in the stability at more alkaline pH values. A soluble substrate, cellotetraose, was shown to stabilize the protein fold both at optimal and alkaline pH. In addition, unfolding of the Cel7A enzyme and the release of the substrate seem to coincide at both acidic and alkaline pH, demonstrated by a change in the fluorescence emission maximum. CD measurements were used to show that the five point mutations (E223S/A224H/L225V/T226A/D262G) that together result in a more alkaline pH optimum [Becker, D., Braet, C., Brumer, H., III, Claeyssens, M., Divne, C., Fagerström, R.B., Harris, M., Jones, T.A., Kleywegt, G.J., Koivula, A., et al. (2001) Biochem. J.356, 19,30], destabilize the protein fold both at acidic and alkaline pH when compared with the wild-type enzyme. In addition, an interesting time-dependent fluorescence change, which was not observed by CD, was detected for the pH mutant. Our data show that in order to engineer more alkaline pH cellulases, a combination of mutations should be found, which both shift the pH optimum and at the same time improve the thermal stability at alkaline pH range. [source]

    Conversion of a glutamate dehydrogenase into methionine/norleucine dehydrogenase by site-directed mutagenesis

    FEBS JOURNAL, Issue 22 2001
    Xing-Guo Wang
    In earlier attempts to shift the substrate specificity of glutamate dehydrogenase (GDH) in favour of monocarboxylic amino-acid substrates, the active-site residues K89 and S380 were replaced by leucine and valine, respectively, which occupy corresponding positions in leucine dehydrogenase. In the GDH framework, however, the mutation S380V caused a steric clash. To avoid this, S380 has been replaced with alanine instead. The single mutant S380A and the combined double mutant K89L/S380A were satisfactorily overexpressed in soluble form and folded correctly as hexameric enzymes. Both were purified successfully by Remazol Red dye chromatography as routinely used for wild-type GDH. The S380A mutant shows much lower activity than wild-type GDH with glutamate. Activities towards monocarboxylic substrates were only marginally altered, and the pH profile of substrate specificity was not markedly altered. In the double mutant K89L/S380A, activity towards glutamate was undetectable. Activity towards l -methionine, l -norleucine and l -norvaline, however, was measurable at pH 7.0, 8.0 and 9.0, as for wild-type GDH. Ala163 is one of the residues that lines the binding pocket for the side chain of the amino-acid substrate. To explore its importance, the three mutants A163G, K89L/A163G and K89L/S380A/A163G were constructed. All three were abundantly overexpressed and showed chromatographic behaviour identical with that of wild-type GDH. With A163G, glutamate activity was lower at pH 7.0 and 8.0, but by contrast higher at pH 9.0 than with wild-type GDH. Activities towards five aliphatic amino acids were remarkably higher than those for the wild-type enzyme at pH 8.0 and 9.0. In addition, the mutant A163G used l -aspartate and l -leucine as substrates, neither of which gave any detectable activity with wild-type GDH. Compared with wild-type GDH, the A163 mutant showed lower catalytic efficiencies and higher Km values for glutamate/2-oxoglutarate at pH 7.0, but a similar kcat/Km value and lower Km at pH 8.0, and a nearly 22-fold lower S0.5 (substrate concentration giving half-saturation under conditions where Michaelis,Menten kinetics does not apply) at pH 9.0. Coupling the A163G mutation with the K89L mutation markedly enhanced activity (100,1000-fold) over that of the single mutant K89L towards monocarboxylic amino acids, especially l -norleucine and l -methionine. The triple mutant K89L/S380A/A163G retained a level of activity towards monocarboxylic amino acids similar to that of the double mutant K89L/A163G, but could no longer use glutamate as substrate. In terms of natural amino-acid substrates, the triple mutant represents effective conversion of a glutamate dehydrogenase into a methionine dehydrogenase. Kinetic parameters for the reductive amination reaction are also reported. At pH 7 the triple mutant and K89L/A163G show 5 to 10-fold increased catalytic efficiency, compared with K89L, towards the novel substrates. In the oxidative deamination reaction, it is not possible to estimate kcat and Km separately, but for reductive amination the additional mutations have no significant effect on kcat at pH 7, and the increase in catalytic efficiency is entirely attributable to the measured decrease in Km. At pH 8 the enhancement of catalytic efficiency with the novel substrates was much more striking (e.g. for norleucine ,,2000-fold compared with wild-type or the K89L mutant), but it was not established whether this is also exclusively due to more favourable Michaelis constants. [source]

    Novel polysialogangliosides of skate brain

    FEBS JOURNAL, Issue 16 2000
    Structural determination of tetra, hexasialogangliosides with a NeuAc-GalNAc linkage, penta
    The gangliosides in the brain of a cartilaginous fish, skate (Bathyraja smirnovi), have been isolated and characterized by means of methylation analysis, antibody binding, enzymatic hydrolysis and MALDI-TOF MS. In addition to gangliosides with known structures (GM2, fucosyl-GM1, GD3, GD2, GT3 and GT2), five polysialogangliosides were isolated and characterized as having the following structures. (1) IV3NeuAc, III6NeuAc, II3NeuAc-Gg4Cer; (2) IV3NeuAc2, III6NeuAc, II3NeuAc-Gg4Cer; (3) IV3NeuAc, III6NeuAc, II3NeuAc2 -Gg4Cer; (4) IV3NeuAc, III6NeuAc, II3NeuAc3 -Gg4Cer; and (5) IV3NeuAc2, III6NeuAc, II3NeuAc3 -Gg4Cer. These structures are ,hybrid-type' which comprise combinations of ,-series and either a, b or c-series structures. Three gangliosides (2), (4) and (5), were novel. The main features of the ganglioside composition of skate brain were an abundance of gangliotriaosyl species, a lack of gangliotetraosyl species (except fucosyl-GM1), and an abundance of hybrid-types. These characteristics closely resemble those in shark brain which we reported previously [Nakamura, K., Tamai, Y. & Kasama, T. (1997) Neurochem. Int.30, 593,604]. Two of the hybrid-type gangliosides (1) and (4), were examined for their neuritogenic activity toward cultured neuronal cells (Neuro-2A), and were found to have more potent activity than nonhybrid-type gangliosides such as GM1. [source]

    Sympathetic control of short-term heart rate variability and its pharmacological modulation

    Jean-Luc Elghozi
    Abstract The static relationship between heart rate (HR) and the activity of either vagal or sympathetic nerves is roughly linear within the physiological range of HR variations. The dynamic control of HR by autonomic nerves is characterized by a fixed time delay between the onset of changes in nerve activity and the onset of changes in HR. This delay is much longer for sympathetically than for vagally mediated changes in HR. In addition, the kinetics of the HR responses shows the properties of a low-pass filter with short (vagal) and long (sympathetic) time constants. These differences might be secondary to differences in nervous conduction times, width of synaptic cleft, kinetics of receptor activation and post-receptor events. Because of the accentuated low-pass filter characteristics of the HR response to sympathetic modulation, sympathetic influences are almost restricted to the very-low-frequency component of HR variability, but the chronotropic effects of vagal stimulation usually predominate over those of sympathetic stimulation in this frequency band. Oscillations in cardiac sympathetic nerve activity are not involved in respiratory sinus arrhythmia (high-frequency component) and make a minor contribution to HR oscillations of approximately 10-s period (low-frequency component of approximately 0.1 Hz), at least in the supine position. In the latter case, HR oscillations are derived mainly from a baroreflex, vagally mediated response to blood pressure Mayer waves. Beta-blockers and centrally acting sympathoinhibitory drugs share the ability to improve the baroreflex control of HR, possibly through vagal facilitation, which might be beneficial in several cardiovascular diseases. [source]

    PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA

    GENES TO CELLS, Issue 10 2002
    Tetsuo Iida
    Background: Proliferating cell nuclear antigen (PCNA) is a ring-shaped protein known as a processivity factor of DNA polymerase ,. In addition to this role, PCNA interacts with a number of other proteins to increase their local concentration at replicated DNA sites. DNA cytosine methyltransferase 1 (Dnmt1), which preserves epigenetic signals by completing the methylation of hemimethylated DNA after DNA replication, has been indicated as one of these PCNA binding proteins by a previous work. However, the molecular mechanisms and functional significance of their association have not yet been studied. Results: Dnmt1 can be readily isolated from nuclear extracts by PCNA affinity chromatography. Studies of the interactions between the two proteins demonstrate that the N-terminal region of Dnmt1, which contains a typical PCNA binding motif, has core PCNA binding activity, and that the remaining portion of the protein exerts a negative influence on the interaction of Dnmt1 with PCNA. The affinity of Dnmt1 for DNA is much higher for DNA bound by PCNA than for free DNA. Furthermore, DNA methylation assays with hemimethylated DNA as a substrate revealed that PCNA clamp-bound DNA is methylated more efficiently by Dnmt1 than is free DNA. Conclusion: These results provide the first biochemical evidence that physical interactions between PCNA and Dnmt1 facilitate the methylation of newly neplicated DNA, on which PCNA remains associated as a functional clamp. [source]

    Topiramate Treatment of Chronic Migraine: A Randomized, Placebo-Controlled Trial of Quality of Life and Other Efficacy Measures

    HEADACHE, Issue 8 2009
    Stephen Silberstein MD
    Objective., To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial. Background., We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated. Methods., Variables analyzed included between-treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache-free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine-Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change. Results., The intent-to-treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate- vs placebo-treated subjects were as follows: for ,25% reduction: 68.6% vs 51.6% (P = .005); ,50%: 37.3% vs 28.8% (P = .093); and ,75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache-free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine-Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine-Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062). Conclusions., In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events. [source]

    Depression and Retirement in Late Middle-Aged U.S. Workers

    Jalpa A. Doshi
    Objective. To determine whether late middle-aged U.S. workers with depression are at an increased risk for retirement. Data Source. Six biennial waves (1992,2002) of the Health and Retirement Study, a nationally representative panel survey of noninstitutionalized 51,61-year-olds and their spouses started in 1992. Study Design. Workers aged 53,58 years in 1994 were followed every 2 years thereafter, through 2002. Depression was coded as lagged time-dependent variables measuring active depression and severity of depression. The main outcome variable was a transition to retirement which was measured using two distinct definitions to capture different stages in the retirement process: (1) Retirement was defined as a transition out of the labor force in the sample of all labor force participants (N=2,853); (2) In addition a transition out of full time work was used as the retirement definition in the subset of labor force participants who were full time workers (N=2,288). Principal Findings. In the sample of all labor force participants, the presence of active depression significantly increased the hazard of retirement in both late middle-aged men (adjusted OR: 1.37 [95 percent CI 1.05, 1.80]) and women (adjusted OR: 1.40 [95 percent CI 1.10, 1.78]). For women, subthreshold depression was also a significant predictor of retirement. In the sample of full time workers, the relationship between depression and retirement was considerably weaker for women yet remained strong for men. Conclusions. Depression and depressive symptoms were significantly associated with retirement in late middle-aged U.S. workers. Policymakers must consider the potentially adverse impact of these labor market outcomes when estimating the cost of untreated depression and evaluating the value of interventions to improve the diagnosis and treatment of depression. [source]

    An efficient therapeutic approach to patients with acute promyelocytic leukemia using a combination of arsenic trioxide with low-dose all-trans retinoic acid

    Guanjun Wang
    Abstract The use of arsenic trioxide (As2O3, ATO) combined with all-trans retinoic acid (ATRA) has recently been reported to induce remission in patients with acute promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly due to the small number of the available cases. In this study, therefore, we present a clinical study using a combination of ATO with low-dose ATRA (LD-ATRA) to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients). Therapeutic outcomes using the ATO/LD-ATRA approach were compared with those of APL patients treated either with ATO alone (65 patients) or ATRA alone (51 patients). The results showed that the ATO/LD-ATRA approach provided significantly better therapeutic outcomes as compared to either ATO or ATRA alone, as evidenced by lower mortality, a higher CR rate and a reduced period to CR. In addition, the toxic side-effects have been no worse with the combined ATO/LD-ATRA treatment than with either ATO or ATRO alone and in some cases have been reduced. These data suggest that the ATO/LD-ATRA regimen is superior to either regimen given alone to patients with APL. Copyright © 2004 John Wiley & Sons, Ltd. [source]

    A fresh look at dry weight

    Jochen RAIMANN
    Abstract The concept of dry weight (DW) is central to dialysis therapy. The most commonly used definition of DW is the weight below which patients become hypotensive on dialysis. However, this definition is dependent on patient symptoms. A more rigorous definition of DW is the body weight at a physiological extracellular volume (ECV) state. Overhydration is an excess in ECV above that found in healthy subjects. In healthy subjects, within extremes of salt intake, ECV may vary between 280 and 340 mL/kg lean body mass. Sodium accumulation is one of the many consequences of renal failure; it results in increased water intake and an increase in ECV, and an accompanying rise in blood pressure with its clinical sequelae, most prominently cardiovascular and cerebrovascular diseases. Recently characterized endogenous digitalis-like factors which are released in response to ECV expansion have extended this traditional picture. Efforts to reduce a positive sodium balance include dietary counseling and avoidance of iatrogenic intradialytic sodium loading, such as dialysate sodium exceeding serum levels, sodium profiling, and intravenous saline. Excess ECV is predominantly located in the interstitial compartment and must be removed during dialysis therapy by ultrafiltration. During this process, interstitial fluid redistributes to the intravascular space via uptake in the capillary bed. In addition to that mechanism, we propose that increased lymphatic flow into the venous system contributes to plasma refilling. Both clinical and technical means are used to assess the presence of DW. Continuous segmental calf bioimpedance is a promising new technology for intradialytic DW diagnosis. [source]