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1.
J Biomech ; 105: 109723, 2020 05 22.
Article in English | MEDLINE | ID: mdl-32151381

ABSTRACT

Approximately one-third of elderly people fall each year with severe consequences, including death. The aim of this study was to identify the most relevant features to be considered to maximize the accuracy of a logistic regression model designed for prediction of fall/mortality risk among older people. This study included 261 adults, aged over 65 years. Men and women were analyzed separately because sex stratification was revealed as being essential for our purposes of feature ranking and selection. Participants completed a 3-m walk test at their own gait velocity. An inertial sensor attached to their lumbar spine was used to record acceleration data in the three spatial directions. Signal processing techniques allowed the extraction of 21 features representative of gait kinematics, to be used as predictors to train and test the model. Age and gait speed data were also considered as predictors. A set of 23 features was considered. These features demonstrate to be more or less relevant depending on the sex of the cohort under analysis and the classification label (risk of falls and mortality). In each case, the minimum size subset of relevant features is provided to show the maximum accuracy prediction capability. Gait speed has been largely used as the single feature for the prediction fall risk among older adults. Nevertheless, prediction accuracy can be substantially improved, reaching 70% in some cases, if the task of training and testing the model takes into account some other features, namely, sex, age and gait kinematic parameters. Therefore we recommend considering sex, age and step regularity to predict fall-risk.


Subject(s)
Gait , Walking Speed , Acceleration , Accidental Falls , Aged , Aged, 80 and over , Biomechanical Phenomena , Female , Humans , Male
2.
Lupus ; 27(10): 1718-1722, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29635998

ABSTRACT

Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such patients.


Subject(s)
Antimalarials/therapeutic use , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Joint Diseases/drug therapy , Lupus Erythematosus, Cutaneous/drug therapy , Lupus Erythematosus, Systemic/drug therapy , Quinacrine/therapeutic use , Adult , Antimalarials/adverse effects , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/adverse effects , Immunosuppressive Agents/adverse effects , Joint Diseases/diagnosis , Joint Diseases/immunology , Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Cutaneous/immunology , Lupus Erythematosus, Discoid/diagnosis , Lupus Erythematosus, Discoid/drug therapy , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Quinacrine/adverse effects , Remission Induction , Retrospective Studies , Smokers , Treatment Outcome
3.
Sci Rep ; 7(1): 16875, 2017 12 04.
Article in English | MEDLINE | ID: mdl-29203902

ABSTRACT

Injection of amniotic fluid stem cells (AFSC) delays the course of progression of renal fibrosis in animals with Alport Syndrome, enhancing kidney function and improving survival. The mechanisms responsible for these protective outcomes are still largely unknown. Here, we showed that vascular endothelial growth factor (VEGF) signaling within the glomeruli of Alport mice is strongly elevated early on in the disease, causing glomerular endothelial cell damage. Intraventricular injected AFSC that homed within the glomeruli showed strong modulation of the VEGF activity, particularly in glomerular endothelial cells. To investigate this phenomenon we hypothesized that extracellular vesicles (EVs) produced by the AFSC could be responsible for the observed renoprotection. AFSC derived EVs presented exosomal and stem cell markers on their surface membrane, including VEGFR1 and VEGFR2. EVs were able to modulate VEGF in glomerular endothelial cells by effectively trapping the excess VEGF through VEGFR1-binding preventing cellular damage. In contrast, VEGFR1/sVEGFR1 knockout EVs failed to show similar protection, thus indicating that VEGF trapping is a potentially viable mechanism for AFSC-EV mediated renoprotection. Taken together, our findings establish that EVs secreted by AFSC could target a specific signaling pathway within the glomerulus, thus representing a new potential glomerulus-specific targeted intervention.


Subject(s)
Endothelial Cells/metabolism , Extracellular Vesicles , Stem Cells/metabolism , Amniotic Fluid/cytology , Animals , Cells, Cultured , Coculture Techniques , Creatinine/blood , Disease Models, Animal , Endothelial Cells/cytology , Endothelial Cells/drug effects , Extracellular Vesicles/metabolism , Kidney Glomerulus/cytology , Mice , Nephritis, Hereditary/metabolism , Nephritis, Hereditary/pathology , Proteinuria/pathology , Signal Transduction , Stem Cells/cytology , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism
4.
Arch Gynecol Obstet ; 295(1): 103-109, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27619683

ABSTRACT

INTRODUCTION: Pelvic floor ultrasound plays a major role in urogynecologic diagnostics. Using 3D ultrasound we can identify integrity of levator ani and measure hiatal area in the axial plane. The main goal of our study was to measure hiatal area on Valsalva in a cohort of urogynecological patients. Furthermore, we aimed to correlate hiatal area with urogynecological symptoms, levator integrity and evaluate cut-off values for pelvic organ prolapse. MATERIALS AND METHODS: In a retrospective analysis, we included 246 patients seen for urogynecological problems in our tertiary urogynecological unit. After a standardized interview and physical examination, a 3D pelvic floor ultrasound was performed. According to the cardinal urogynecological symptoms and signs, patients were categorized into three groups: pelvic organ prolapse, stress urinary incontinence and overactive bladder symptoms. RESULTS: Median age of our study population was 66 (range 29-94) years, median parity was 2.1 (range 0-9) with 17 (6.9 %) nulliparous women. Symptoms of overactive bladder in 71.1 % were most common, followed by 54.5 % symptoms of stress incontinence and 32.1 % symptoms of prolapse. On examination 49.2 % showed signs of prolapse. Levator avulsions on 3D ultrasound were detected in 20.7 %. Hiatal area was normally distributed with a median of 28.7 cm2 (range 10.4-50.0 cm2). Patients with levator avulsion had a significantly larger hiatal area (p < 0.001). Also patients with signs of prolapse had a significantly larger hiatal area (p < 0.001). There was no correlation between hiatal area and symptoms of overactive bladder (p = 0.374). Although not reaching statistical significance there was evidence of a smaller hiatal area for patients with stress incontinence (p = 0.016). In our cohort there were 33.7 % (83) women without ballooning, 27.2 % (67) showed mild, 18.3 % (45) moderate, 12.3 % (30) marked and 8.5 % (21) severe ballooning. The ROC curve analysis for hiatal area on patients with prolapse yielded an AUC of 0.755 [95 % CI (0.696-0.814)]. Using the Youden-Index we obtained 27.53 cm2 as a cut-off with a sensitivity of 0.70 and a specificity of 0.69. DISCUSSION: Hiatal area is a new repeatable diagnostic parameter. Its clinical application could improve our understanding of the pathophysiology of pelvic organ prolapse as a form of hiatal hernia.


Subject(s)
Pelvic Floor/physiopathology , Pelvic Organ Prolapse/complications , Ultrasonography/methods , Urinary Incontinence, Stress/physiopathology , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Pelvic Floor Disorders/complications , Retrospective Studies
5.
Geburtshilfe Frauenheilkd ; 75(7): 719-722, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26257409

ABSTRACT

This case report shows that 3D perineal ultrasound can be superior to clinical examination and routine 2D perineal ultrasound in the detection of an unusual subpubic tumor. A 73-year-old female patient was referred to our urogynecological outpatient unit complaining of over-active bladder symptoms and voiding dysfunction for 3 years. Gynecological examination found no signs of pelvic organ prolapse or abnormality in the vaginal cavity. Routine 2D perineal ultrasound showed substantial residual urine (ca. 300 ml on catheter) and limited bladder neck mobility, but no signs of pelvic organ prolapse. Use of standardized 3D perineal ultrasound revealed a 24 × 26 × 32 mm spherical, hypoechoic tumor below the pubic symphysis between the distal urethra and the pubic bones. This structure was mistaken for the pubic symphysis in the midline on 2D ultrasound performed earlier. At surgery, the tumor was completely excised through a vaginal incision between the urethra and the pubic symphysis. After an uneventful postoperative recovery the patient developed de-novo stress urinary incontinence, which was corrected successfully by the insertion of a retropubic tension-free suburethral sling after an interval of 8 weeks. After a further follow-up of 8 weeks the patient reported well-being, urinary continence and no voiding dysfunction; no abnormalities were found on examination. In conclusion, 3D perineal ultrasound is a useful additional tool for the diagnostic workup of bladder outlet obstruction.

6.
J Appl Microbiol ; 119(1): 253-62, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25943582

ABSTRACT

AIMS: To develop a gentle ablation technique to recover Listeria monocytogenes biofilms from stainless steel (SS) and polytetrafluoroethylene (PTFE) surfaces by using compressed air and water injection. METHODS AND RESULTS: Biofilms were grown for 4, 24 and 48 h or 7 days and a compressed air and water flow at 2, 3 and 4 bars was applied for cell removal. Collected cells were quantified for total/dead by staining with SYTO 9/PI double staining and cultivable populations were determined by plating onto brain heart infusion (BHI) agar, while coupon surfaces also were stained with DAPI to quantify in situ the remaining cells. The recovery efficiency was compared to that of conventional swabbing. Results showed that the air/water ablation is able to collect up to 98·6% of cells from SS surfaces while swabbing only recovered 11·2% of biofilm. Moreover, air/water ablation recovered 99·9% of cells from PTFE surfaces. CONCLUSIONS: The high recovery rate achieved by this technique, along with the fact that cells were able to retain membrane integrity and cultivability, indicate that this device is suitable for the gentle recovery of viable L. monocytogenes biofilm cells. SIGNIFICANCE AND IMPACT OF THE STUDY: This work presents a highly efficient technique to remove, collect and quantify L. monocytogenes from surfaces commonly used in the food industry, which can thus serve as an important aid in verifying cleaning and sanitation as well as in reducing the likelihood of cross-contamination events.


Subject(s)
Bacteriological Techniques/methods , Biofilms , Listeria monocytogenes/growth & development , Food Contamination/analysis , Food-Processing Industry/instrumentation , Listeria monocytogenes/isolation & purification , Listeria monocytogenes/physiology , Polytetrafluoroethylene/analysis , Stainless Steel/analysis
7.
Dig Dis Sci ; 56(11): 3288-95, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21573941

ABSTRACT

BACKGROUND: Abdominal pain, that characterizes irritable bowel syndrome (IBS) together with bloating and disordered defecation, is mainly related to a visceral hypersensitivity due to an increase of TRPV(1) nociceptive nerve fiber activity. AIM: As capsaicin contained in red pepper is able to desensitize the TRPV(1) fibres, we evaluated whether the red pepper oral administration can decrease the symptoms of visceral hypersensitivity in IBS patients. METHODS: The study was performed on 50 patients with IBS diagnosed following Rome II criteria. After a 2-week washout period, 23 patients were planned to receive 4 pills/day, for 6 weeks randomly and in a double blind manner, each containing 150 mg of red pepper powder with a coat that dissolves in the colon, and 27 patients placebo. The patients scored each day in a diary the abdominal pain and bloating intensities following the 5-point Likert scale. The weekly symptom mean scores and the final patient subjective evaluation on treatment effectiveness were statistically compared among groups and intra-groups with appropriate tests. RESULTS: Eight patients dropped from the study: 6 in the red pepper group for abdominal pain and 2 in the placebo group. In 8 patients, the pills were reduced to 2/day, because of the abdominal pain at the onset of treatment. The intra-group comparisons showed that in patients taking red pepper the abdominal pain and bloating mean score values of the last weeks of treatment were significantly improved with respect to pre-treatment values, unlike patients taking placebo. The final patient subjective evaluation on the treatment effectiveness showed that red pepper group scored significantly better than placebo. CONCLUSIONS: The results of this preliminary study indicate that the chronic administration of red pepper powder in IBS patients with enteric-coated pills was significantly more effective than placebo in decreasing the intensity of abdominal pain and bloating and was considered by the patients more effective than placebo.


Subject(s)
Capsaicin/therapeutic use , Capsicum , Irritable Bowel Syndrome/drug therapy , Phytotherapy , Sensory System Agents/therapeutic use , Adult , Double-Blind Method , Female , Humans , Male , Plant Preparations/therapeutic use
8.
J Dairy Sci ; 89(11): 4096-104, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17032996

ABSTRACT

The inactivation kinetics of a lipase from Pseudomonas fluorescens (EC 3.1.1.3.) were studied in a simulated skim milk ultrafiltrate treated with high-intensity pulsed electric fields. Samples were subjected to electric field intensities ranging from 16.4 to 27.4 kV/cm for up to 314.5 micros, thus achieving a maximum inactivation of 62.1%. The suitability of describing experimental data using mechanistic first-order kinetics and an empirical model based on the Weibull distribution function is discussed. In addition, different mathematical expressions relating the residual activity values to field strength and treatment time are supplied. A first-order fractional conversion model predicted residual activity with good accuracy (A(f) = 1.018). A mechanistic insight of the model kinetics was that experimental values were the consequence of different structural organizations of the enzyme, with uneven resistance to the pulsed electric field treatments. The Weibull model was also useful in predicting the energy density necessary to achieve lipase inactivation.


Subject(s)
Electricity , Lipoprotein Lipase/metabolism , Milk/microbiology , Models, Biological , Pseudomonas fluorescens/enzymology , Animals , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Kinetics , Lipoprotein Lipase/chemistry , Milk/chemistry , Milk/enzymology , Ultrafiltration
9.
Pesqui. bras. odontopediatria clín. integr ; 6(2): 137-141, Mai.-Ago.2006.
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-853704

ABSTRACT

Este trabalho foi realizado com objetivo de avaliar por meio de ensaio de tração, a resistência adesiva de 4 sistemas adesivos de frasco único à dentina de dentes decíduos.Método: Foram utilizados 20 molares decíduos do Banco de Dentes Humanos da Faculdade de Odontologia da Universidade de São Paulo seccionados no sentido mésiodistale incluídos em resina acrílica autopolimerizável com suas faces vestibulares, palatais ou linguais voltadas para a superfície externa. Os dentes tiveram suas superfícies vestibulares ou linguais/palatais desgastadas até a obtenção de superfícies dentinárias planas e foram divididos aleatoriamente em 4 grupos. G1: Prime & Bond NT (DentsplyCaulk); G2: Optibond Solo (Kerr); G3: Excite (Vivadent) e G4:Single Bond (3M). Os sistemas adesivos foram aplicados de acordo com as instruções de cada fabricante. O mesmo material restaurador (Filtek Z 250-3M) foi utilizado em todos os grupos. Os corpos de prova foram conservados em águad estilada durante 24 horas e depois submetidos a ensaio de tração. Resultados: As menores médias foram apresentadas pelos grupos G2 e G3 e as maiores médias pelos grupos G1 eG4. Conclusão: Nas condições desse estudo o sistema adesivo Single Bond (3M) e Prime Bond NT (Dentsply Caulk)apresentaram melhor resistência adesiva à dentina de dentes decíduos.


Subject(s)
Humans , Dentin-Bonding Agents/analysis , Tooth, Deciduous , Dentin , Tensile Strength , Analysis of Variance
10.
J Dairy Sci ; 89(3): 905-11, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16507684

ABSTRACT

The effect of high-intensity pulsed electric fields (HI-PEF) processing (35.5 kV/cm for 1,000 or 300 micros with bipolar 7-micros pulses at 111 Hz; the temperature outside the chamber was always < 40 degrees C) on microbial shelf life and quality-related parameters of whole milk were investigated and compared with traditional heat pasteurization (75 degrees C for 15 s), and to raw milk during storage at 4 degrees C. A HIPEF treatment of 1,000 micros ensured the microbiological stability of whole milk stored for 5 d under refrigeration. Initial acidity values, pH, and free fatty acid content were not affected by the treatments; and no proteolysis and lipolysis were observed during 1 wk of storage in milk treated by HIPEF for 1,000 micros. The whey proteins (serum albumin, beta-lactoglobulin, and alpha-lactalbumin) in HIPEF-treated milk were retained at 75.5, 79.9, and 60%, respectively, similar to values for milk treated by traditional heat pasteurization.


Subject(s)
Food Handling/methods , Milk/microbiology , Animals , Cold Temperature , Colony Count, Microbial , Electricity , Electrophoresis, Polyacrylamide Gel , Fats/analysis , Fatty Acids, Nonesterified/analysis , Food Preservation , Hot Temperature , Hydrogen-Ion Concentration , Lactalbumin/analysis , Lactoglobulins/analysis , Milk Proteins/analysis , Serum Albumin/analysis , Time Factors , Whey Proteins
11.
Pesqui. bras. odontopediatria clín. integr ; 5(3): 253-259, set.-dez. 2005. graf
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-872736

ABSTRACT

Avaliar a citotoxicidade in vitro do novo produtoutilizando as concentrações de 2 porcento, 4 porcento, 6 porcento e 8 porcento de papaínaem solução contendo 0,5 porcento de cloramina. Método: Osmateriais foram colocados em lamínulas de vidro e em seguidadepositados sobre células em cultura. Utilizaram-sefibroblastos NIH-3T3, plaqueados em 1X104 células por placade Petri. Nas culturas controle as lamínulas de vidro foramadicionadas sem substância. Executaram-se testes de longoprazo, nos períodos experimentais de 1, 3, 5 e 7 dias. Nessesperíodos efetuou-se a contagem celular, em triplicata para cadasubstância testada, pelo método de exclusão de célulascoradas pelo azul de Trypan, que forneceram dados paracurvas de crescimento e de viabilidade celular. Resultados:Observou-se que durante todo o trabalho todos os gruposexperimentais apresentaram viabilidade celular entre 80 e100 porcento, e as diferentes concentrações de papaína utilizadas nãoapresentaram diferença estatística significante nadeterminação da viabilidade celular. Conclusão: O novobiomaterial, nas diferentes concentrações, não demonstrou sercitotóxico in vitro em cultura de fibroblastos


Subject(s)
Humans , Animals , Mice , Dental Caries , Dental Materials/analysis , Papain , Dentin/injuries , Statistics, Nonparametric , In Vitro Techniques , Toxicity
12.
J Physiol Pharmacol ; 56(2): 179-93, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15985701

ABSTRACT

Exposure to LBNP results in body fluid shift to lower extremities similarly as under influence of orthostatic stress. In susceptible persons it leads to syncope. For better understanding why certain individuals are more susceptible to orthostatic challenges it seemed necessary to collect more data on hemodynamic and neuroendocrine adjustments occurring before onset of presyncopal symptoms Accordingly, in this study heart rate (HR), blood pressure (BP), stroke volume (SV), cardiac output (CO), hematocrit, plasma catecholamines, adrenomedullin, ACTH and plasma renin activity (PRA) were measured in 24 healthy men during graded LBNP (-15, -30 and -50 mmHg). Thirteen subjects completed the test (HT group) whereas 11 had presyncope signs or symptoms at -30 mmHg or at the beginning of -50 mmHg (LT group). Comparison of these groups showed that LT subjects had lower baseline total peripheral resistance and higher plasma adrenomedullin. During LBNP plasma catecholamine and PRA increases were even greater in LT than in HT group while plasma adrenomedullin elevations were similar in both groups. Plasma ACTH increased only in LT group following presyncope symptoms. Low tolerant group showed more rapid decline of SV and CO than HT subjects from the beginning of LBNP. It is suggested that measurements of SV at the level of LBNP which did not evoke any adverse symptoms may be of predictive value for lower orthostatic tolerance.


Subject(s)
Blood Pressure , Heart Rate , Lower Body Negative Pressure , Adrenocorticotropic Hormone/blood , Adrenomedullin , Adult , Cardiac Output , Humans , Male , Norepinephrine/blood , Peptides/blood
14.
J Sports Med Phys Fitness ; 41(3): 324-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11533562

ABSTRACT

BACKGROUND: This study examined the hypothesis that prolonged (12 hrs) stimulation of adrenergic receptors by adrenaline and their blockade by regitine (alpha-blockade) or propranolol (beta-blockade) affect lactate thresh-old (T(LA)) and exercise tolerance in rats. METHODS: Twenty-four untrained male Wistar rats performed a multistage running test on a treadmill with an intensity increased from 13 m/min to the maximum speed. After a control exercise test the animals were devided into three groups implanted s.c. with: 1) adrenaline; 2) propranolol and 3) regitine tablets. Twelve hours after the tablet implantation the exercise was repeated. Both before the exercise test and at the end of each 2-min loads blood lactate [LA] was measured to evaluate T(LA). RESULTS: Prolonged adrenaline excess resulted in reduced maximal running speed and shifted T(LA) towards lower exercise intensities than in the control test. Both alpha- and beta-adrenergic blockade reduced the work load at which T(LA) occurred, without changing the maximum running speed and maximal blood LA concentration. Blood [LA] at the lactate threshold ([LA] at T(LA)) was significantly higher in hyperadrenalinemic than in control rats, whilst under beta-blockade it was lowered in comparison with control values. Alpha-adrenergic blockade had no effect on [LA] at T(LA), but at the higher exercise intensities blood [LA] exceeded the respective control values. CONCLUSIONS: The present study demonstrated that prolonged excess of adrenaline reduces the maximum power output and T(LA). The former effect seems to be a result of simultaneous stimulation of both types of adrenergic receptors.


Subject(s)
Adrenergic Agonists/pharmacology , Adrenergic Antagonists/pharmacology , Exercise Tolerance/physiology , Lactates/blood , Receptors, Adrenergic/physiology , Animals , Drug Implants , Epinephrine/pharmacology , Exercise Tolerance/drug effects , Male , Phentolamine/pharmacology , Propranolol/pharmacology , Rats , Rats, Wistar , Running/physiology
15.
Brain Res Mol Brain Res ; 84(1-2): 52-7, 2000 Dec 08.
Article in English | MEDLINE | ID: mdl-11113531

ABSTRACT

The effect of treatment of rats with pivagabine (4-[(2,2-dimethyl-1-oxopropyl) amino] butanoic acid) for 4 days on the abundance of corticotropin-releasing factor (CRF) mRNA in the brain was investigated. Such treatment resulted in dose-dependent (100-300 mg/kg, i.p.) increases in the amount of CRF mRNA in both the hypothalamus and cerebral cortex. The maximal increases were thus apparent with the dose of 300 mg/kg in the hypothalamus (+108%) and cerebral cortex (+49%) 30 or 60 min, respectively, after the last drug injection. Foot-shock stress administered 30 min after the final drug injection had no effect on the pivagabine-induced increases in the abundance of CRF mRNA in the hypothalamus or cerebral cortex. Such stress also had no effect on the amounts of CRF mRNA in these brain regions of vehicle-treated rats. These results demonstrate that pivagabine increases the amount of CRF mRNA in both the hypothalamus and cerebral cortex of rats, effects that might be relevant to the action of this drug in preventing the stress-induced changes in CRF hypothalamic concentration.


Subject(s)
Cerebral Cortex/drug effects , Corticotropin-Releasing Hormone/genetics , Gene Expression Regulation/drug effects , Hypothalamus/drug effects , Psychotropic Drugs/pharmacology , gamma-Aminobutyric Acid/analogs & derivatives , gamma-Aminobutyric Acid/pharmacology , Animals , Anticonvulsants/pharmacology , Cerebral Cortex/metabolism , Electroshock , Hypothalamus/metabolism , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Stress, Physiological/physiopathology
16.
Life Sci ; 67(8): 949-58, 2000 Jul 14.
Article in English | MEDLINE | ID: mdl-10946854

ABSTRACT

The impact of three different magnesium diets (70, 1,000 and 9,000 ppm) on total, ionized and bound magnesium as well as ionized calcium in serum and total calcium and magnesium in femoral bone, skeletal muscle, heart and liver of male Sprague-Dawley rats was investigated. The percentage of ionized serum magnesium was unproportionally high in rats fed a low magnesium (70 ppm) diet. Femoral magnesium was correlated with ionized and total serum magnesium. In contrast, there was generally no correlation between total serum magnesium and the magnesium fractions in skeletal muscle, heart and liver. In rats fed the magnesium deficient diet, total cardiac concentration of magnesium was even significantly increased along with total calcium content, while there were no effects on total muscle and liver magnesium. Within the single groups, ionized serum calcium was never proportional to dietary magnesium, but in all three magnesium diet groups together, it was inversely correlated with dietary magnesium. Moreover, ionized serum calcium was inversely correlated with both ionized and total serum magnesium. In all 3 groups together, the concentrations of total calcium and magnesium in heart and skeletal muscle were correlated, within the single groups correlation existed only in the 1000 ppm group. Magnesium influx via calcium channels during low magnesium intake has been seen in non cardiac tissues [35,36], but nothing similar is known about non selective channels for divalent cations in the heart [33]. Thus, magnesium uptake by cardiac cells along with calcium seems to be possible, especially at low intracellular magnesium concentrations, but is still poorly investigated. We suggest that the calcium-antagonistic effect of magnesium is related to the turnover rate of magnesium rather than to its tissue concentrations.


Subject(s)
Calcium/metabolism , Magnesium/administration & dosage , Animals , Bone and Bones/metabolism , Diet , Magnesium/metabolism , Male , Muscle, Skeletal/metabolism , Myocardium/metabolism , Rats , Rats, Sprague-Dawley
17.
Eur J Endocrinol ; 143(2): 273-7, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10913948

ABSTRACT

OBJECTIVE: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. DESIGN: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h after the administration of CGP-12177 or NE. METHODS: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500 g for 10 min at 4 degrees C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 microCi [(125)I]T4. Aliquots were chromatographed on paper for the measurement of [(125)I]T4 and its deiodinated subproducts. RESULTS: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. CONCLUSIONS: The results indicate that CGP-12177 stimulated the in vivo activation of 5'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.


Subject(s)
Adipose Tissue, Brown/drug effects , Adrenergic beta-Agonists/pharmacology , Iodide Peroxidase/metabolism , Propanolamines/pharmacology , Sympathectomy , Thyroxine/metabolism , Adipose Tissue, Brown/metabolism , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Cold Temperature , Drug Implants , Enzyme Activation/drug effects , Iodine/metabolism , Iodine Radioisotopes , Male , Norepinephrine/pharmacology , Prazosin/pharmacology , Propanolamines/administration & dosage , Propranolol/pharmacology , Rats , Rats, Wistar
18.
Mol Pharmacol ; 57(6): 1262-70, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10825399

ABSTRACT

Rat cerebellar granule cells were cultured for 5 days with progesterone, resulting in the conversion of progesterone to allopregnanolone, a potent and efficacious modulator of gamma-aminobutyric acid (GABA) type-A receptors, as well as in decreases in the abundance of GABA(A) receptor alpha(1), alpha(3), alpha(5), and gamma(2) subunit mRNAs. These effects were accompanied by decreases in the efficacies of diazepam and the beta-carboline DMCM with regard to modulation of GABA-evoked Cl(-) currents. Withdrawal from such progesterone treatment resulted in a rapid and selective increase in the abundance of the GABA(A) alpha(4) subunit mRNA that was associated with a restoration of receptor sensitivity to the negative modulatory action of DMCM, a positive receptor response to flumazenil, and continued reduced responsiveness of receptors to diazepam. Prevention of allopregnanolone synthesis by the 5alpha-reductase inhibitor finasteride also prevented the changes in both GABA(A) receptor gene expression and receptor function elicited by progesterone treatment and withdrawal.


Subject(s)
Cerebellum/metabolism , Gene Expression Regulation/drug effects , Pregnanolone/biosynthesis , Progesterone/pharmacology , Receptors, GABA-A/biosynthesis , Animals , Cells, Cultured , Cerebellum/cytology , Cerebellum/drug effects , Electrophysiology , Rats , Receptors, GABA-A/genetics , Xenopus laevis
19.
Life Sci ; 66(1): 11-8, 2000.
Article in English | MEDLINE | ID: mdl-10658919

ABSTRACT

The aim of our study was to assess the influence of intraoperative hypoxic stress -unavoidably brought about by so called Pringle maneuver - on free and conjugated catecholamines during major hepatic resection. Judging from earlier results of fatigue-experiments in rats we also wanted to check the relationship between of poor general preoperative condition and conspicuously low triglyceride serum concentrations. The study included 26 patients with primary and secondary liver tumors. The mean age was 54 years (range 27-79). Twenty-one patients had segmental liver resections, 3 had hemihepatectomies and 2 hydatid cysts were treated by cystectomy. Blood samples were taken 2 days before and throughout surgery. Catecholamine plasma values were determined by high performance liquid chromatography. Statistical comparisons were made by t-test, ANOVA and chi square test. Free plasma catecholamines increased significantly during prolonged intraoperative ischemia (Pringle time 50-125 minutes). Patients with elevated intraoperative catecholamines had a significant correlation to postoperative episodes of tachycardia, and prolonged hospital stay. On the other hand, we could also see postoperative tachycardias in patients with short Pringle times (18-49 minutes) but with decreased preoperative serum triglycerides as an indicator of chronic stress and reduced general condition. Intraoperative hypoxic stress is associated with increased catecholamine values. Elevated catecholamines may well cause postoperative sinus-tachycardias (mean 20 hours) and are strongly related to postoperative liver failure and prolonged hospital stay.


Subject(s)
Catecholamines/metabolism , Ischemia/complications , Liver Neoplasms/surgery , Liver/blood supply , Postoperative Complications/etiology , Tachycardia/etiology , Adult , Aged , Female , Humans , Intraoperative Period , Male , Middle Aged , Postoperative Complications/metabolism , Preoperative Care , Tachycardia/metabolism
20.
Eur J Clin Invest ; 29(7): 582-7, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10411663

ABSTRACT

BACKGROUND: It has previously been found that in cardiac risk patients undergoing non-cardiac surgery post-operative cardiac complications are correlated with high post-operative serum levels of troponin T (TNT) and troponin I (TNI). We investigated whether perioperative changes in the release of free (fCAs) and conjugated catecholamines (cCAs) correlate with the increased serum level of TN (TN upward arrow). MATERIALS AND METHODS: Plasma levels of CAs were determined in 28 patients at risk for or with definite coronary artery disease. Blood sampling was performed in the morning on the day before surgery, on the day of surgery before induction of anaesthesia and until the fifth post-operative day for measurement of CAs by high-performance liquid chromatography. RESULTS: The plasma concentrations of free and conjugated noradrenaline (fNA and cNA) as well as of free and conjugated adrenaline (fA and cA) were increased significantly in TN upward arrow patients post-operatively. The plasma levels of free as well as of conjugated NA and A in TN upward arrow patients were significantly higher than in TN0 patients over the whole post-operative period. CONCLUSION: This study demonstrates that increased post-operative release of fNA and fA as well as of cNA and cA correlates with high post-operative serum levels of troponins in cardiac risk patients undergoing non-cardiac surgery.


Subject(s)
Catecholamines/blood , Coronary Disease/epidemiology , Elective Surgical Procedures , Heart Diseases/epidemiology , Aged , Angina Pectoris , Angioplasty, Balloon, Coronary , Blood Pressure , Coronary Artery Bypass , Dopamine/blood , Epinephrine/blood , Female , Heart Failure , Heart Rate , Humans , Male , Middle Aged , Myocardial Infarction , Norepinephrine/blood , Postoperative Period , Risk Factors
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