ABSTRACT
Bacterial lipopolysaccharide (LPS) induces general inflammation, by activating pathways involving cytokine production, blood coagulation, complement system activation, and acute phase protein release. The key cellular players are leukocytes and endothelial cells, that lead to tissue injury and organ failure. The aim of this study was to explore the anti-inflammatory, antioxidant, and cytoprotective properties of two bile acids, ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in LPS-induced endotoxemia in rats. The experiment involved six distinct groups of Wistar rats, each subjected to different pretreatment conditions: control and LPS groups were pretreated with propylene glycol, as a bile acid solvent, while the other groups were pretreated with UDCA or CDCA for 10 days followed by an LPS injection on day 10. The results showed that both UDCA and CDCA reduced the production of pro-inflammatory cytokines: TNF-α, GM-CSF, IL-2, IFNγ, IL-6, and IL-1ß and expression of nuclear factor-κB (NF-κB) induced by LPS. In addition, pretreatment with these bile acids showed a positive impact on lipid profiles, a decrease in ICAM levels, an increase in antioxidant activity (SOD, |CAT, GSH), and a decrease in prooxidant markers (H2O2 and O2-). Furthermore, both bile acids alleviated LPS-induced liver injury. While UDCA and CDCA pretreatment attenuated homocysteine levels in LPS-treated rats, only UDCA pretreatment showed reductions in other serum biochemical markers, including creatine kinase, lactate dehydrogenase, and high-sensitivity troponin I. It can be concluded that both, UDCA and CDCA, although exerted slightly different effects, can prevent the inflammatory responses induced by LPS, improve oxidative stress status, and attenuate LPS-induced liver injury.
ABSTRACT
OBJECTIVES: This study aimed at investigating poverty and other correlates of childhood underweight and obesity in two urban regions with lower (Podgorica, Montenegro) and higher economic development (Osijek, Croatia). STUDY DESIGN: Comparative study. METHODS: A comparative study was conducted on 693 children (52% boys), aged 7 years old (224 from Podgorica and 469 from Osijek). Parents completed the study-specific questionnaire on relevant factors for children's nutritional status. We measured children's height and weight and calculated their body mass index (BMI). International Obesity Task Force cut-off values of BMI were used to assess children's nutritional status. Subjective social position was assessed by the Mac Arthur scale. RESULTS: There were more underweight children in Osijek compared with Podgorica, both among boys (5.5% vs. 1.6%) and girls (6.9% vs. 1.0%). Obesity was more frequent in Podgorica than Osijek, both among boys (11.3% vs. 5.9%) and girls (10.0% vs. 4.3%). However, poverty in two cities diminished observed differences in children's nutritional status. The odds for child underweight decreased by 12.2%, while the odds for obesity increased by 3.6% per each paternal BMI unit. The frequency of child obesity was lowered per each step higher on the Mac Arthur scale and with breastfeeding by 23.2% and 68.0%, respectively. CONCLUSIONS: We show that a higher economic development is related to less obese children but more underweight children. However, poverty seems to impact nutritionally all children equally, regardless of the regional economic development. Paternal and not maternal BMI is relevant for both extremes in children's nutritional status. Breastfeeding and higher social position independently protect from child obesity.
Subject(s)
Pediatric Obesity/epidemiology , Poverty/statistics & numerical data , Thinness/epidemiology , Body Mass Index , Body Weight , Child , Croatia/epidemiology , Female , Humans , Male , Montenegro/epidemiology , Nutritional Status , Sex Factors , Socioeconomic Factors , Surveys and Questionnaires , Urban PopulationABSTRACT
OBJECTIVE: The study aimed to assess the psychometric properties of the Menopause-specific Quality of Life Questionnaire (MENQOL) in Serbian climacteric women. METHODS: Two hundred mid-aged (40-65 years) women filled out a general sociodemographic and medical questionnaire, the MENQOL, the Short Form-36 questionnaire (SF-36), and Beck's Depression Inventory (BDI). The MENQOL was translated according to recommended methodology and its psychometric properties (internal consistency, discriminant, construct and criterion validity, factor and Rasch analyses) were assessed. RESULTS: Cronbach's alpha coefficient for the Serbian MENQOL was 0.957 (Vasomotor =0.917, Psychosocial =0.907, Physical =0.928, Sexual =0.913). Corrected item-total correlation coefficients were >0.50 for all items. Factor analysis extracted six domains with total variance of 72.02%. Beside the four original domains, two new domains were observed: Attractiveness and Pain. Factor loadings for all items were appropriate (>0.4). The MENQOL correlated with the SF-36 and BDI total scores, suggesting good criterion validity. Rasch analysis showed adequate reliability (item =0.91; person =0.79) and separation (item =1.95; person =3.21) indexes, proving good reproducibility and reliability of the Serbian MENQOL. All items had infit and outfit mean squares in the standard accepted range. CONCLUSION: Principal component analysis showed somewhat different constructs from the original scale. However, Rasch analysis confirmed that the MENQOL represents a good metric instrument for menopausal symptoms.
Subject(s)
Menopause/psychology , Psychometrics , Quality of Life , Female , Humans , Middle Aged , Psychiatric Status Rating Scales , Reproducibility of Results , Serbia , Surveys and Questionnaires , Women's HealthABSTRACT
BACKGROUND: Introducing patient safety and quality improvement science to medical students is integral to improving healthcare. However, developing and implementing a patient safety curriculum can be challenging in a medical school curriculum that is already densely packed. Our aim was to develop and evaluate the impact of a workshop introducing patient safety and quality improvement science to a large class of first-year medical students. METHOD: As a part of an evolving longitudinal patient safety curriculum, an introductory workshop on patient safety was integrated into an anatomy course. A high impact event (a simulated "retained sponge" discovery during an anatomy dissection lab) was used to introduce medical error. The educational session which followed consisted of a presentation by an interprofessional team utilizing the retained sponge as example of an error. Use of safety tools was introduced and quality improvement science was discussed using the evolution of methods to decrease retained foreign objects during surgery. A patient's story told by a close family member about the personal impact of medical errors was presented. Students then participated in an interactive breakout activity and completed a module on safety. The impact of the workshop was assessed through pre- and post- session tests. RESULTS: Quantitative and qualitative evaluation reflected a positive effect of the session in improving students' safety knowledge and attitudes. Students' mean total knowledge improved from 7.58 to 8.98 (p = 0.000). Mean total attitudes score improved from 47.73 to 50.56 (p = 0.000). Students' comments after the workshop reflected increased awareness and appreciation of the importance of addressing medical errors. CONCLUSION: A workshop introducing patient safety and quality improvement to first year medical students improved knowledge and attitudes regarding safety and increased awareness of the importance of addressing medical errors in their future careers. Integrating patient safety education into an existing foundational science course is a model for teaching patient safety at other medical schools.
Subject(s)
Curriculum , Education, Medical, Undergraduate/methods , Foreign Bodies , Medical Errors/prevention & control , Models, Educational , Patient Safety , Surgical Sponges , Attitude of Health Personnel , Cadaver , Educational Measurement , Humans , Quality Improvement , Surveys and QuestionnairesABSTRACT
Recent theoretical and empirical work has focused on the variability of network dynamics in maturation. Such variability seems to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into healthy aging. Two different data sets, one EEG (total n = 48, ages 18-72) and one magnetoencephalography (n = 31, ages 20-75) were analyzed for such spatiotemporal dependency using multiscale entropy (MSE) from regional brain sources. In both data sets, the changes in MSE were timescale dependent, with higher entropy at fine scales and lower at more coarse scales with greater age. The signals were parsed further into local entropy, related to information processed within a regional source, and distributed entropy (information shared between two sources, i.e., functional connectivity). Local entropy increased for most regions, whereas the dominant change in distributed entropy was age-related reductions across hemispheres. These data further the understanding of changes in brain signal variability across the lifespan, suggesting an inverted U-shaped curve, but with an important qualifier. Unlike earlier in maturation, where the changes are more widespread, changes in adulthood show strong spatiotemporal dependence.
Subject(s)
Aging , Brain Mapping , Brain Waves/physiology , Brain/physiology , Acoustic Stimulation , Adolescent , Adult , Aged , Electroencephalography , Entropy , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Magnetoencephalography , Male , Middle Aged , Nonlinear Dynamics , Photic Stimulation , Young AdultABSTRACT
OBJECTIVE: The aim of this study was to translate the Women's Health Questionnaire (WHQ) into the Serbian language and assess its validity and reliability in a population of Serbian menopausal women. METHODS: The study included peri- and postmenopausal women from two Community Health Centers in Belgrade. Women filled out the WHQ, the Short Form-36 questionnaire (SF-36) and Beck's Depression Inventory (BDI). The WHQ was translated according to recommended methodology for cultural adaptation of questionnaires and its psychometric characteristics (internal consistency, inter-rater reliability, factor analysis, sensitivity, discriminant, construct and criterion validity) were tested. RESULTS: In the Serbian population, the mean values of the WHQ domains were mostly comparable with reference Mediterranean countries. Whole-scale Cronbach's α was 0.838. Moreover, five WHQ domains had a value of Cronbach's α above the acceptable limit. There were no significant differences in WHQ scores between our two investigators. On exploratory factor analysis, we obtained ten factors (two items formed a new factor - 'Menstrual pathology'). Almost all SF-36 domains were significantly associated with WHQ domains, while the BDI was associated with domains: depressive mood, anxiety and sleep problems. Based on ROC analysis, WHQ is slightly more reliable for perimenopausal than postmenopausal Serbian women. CONCLUSION: The Serbian version of the WHQ showed very good reliability and validity in assessment of quality of life among menopausal women. The WHQ is applicable for both peri- and postmenopausal women.
Subject(s)
Health Surveys , Menopause , Quality of Life , Surveys and Questionnaires , Women's Health , Adult , Aged , Cross-Sectional Studies , Female , Humans , Menopause/physiology , Menopause/psychology , Middle Aged , Psychometrics , Reproducibility of Results , Serbia , TranslationsABSTRACT
OBJECTIVE: The aim of this study was to investigate the hypolipidemic effects of carnosine and a commercial carnosine supplement on lipid status, liver and kidney function, and inflammation associated with dyslipidemia in rats with high-fat diet-induced hyperlipidemia. MATERIALS AND METHODS: The study was conducted on adult male Wistar rats, divided into control and experimental groups. Animals were kept in standard laboratory conditions and according to groups were treated with saline, carnosine, carnosine dietary supplement, simvastatin, and their combinations. All substances were prepared fresh every day and used by oral gavage. RESULTS: Treatment with a carnosine-based supplement significantly improved total and LDL cholesterol levels in serum, especially in the combination with simvastatin as a conventional drug in dyslipidemia treatment. The effect of carnosine on the metabolism of triglycerides was not as evident as in the case of cholesterol. Nevertheless, the values of the atherogenic index showed that the combinations of carnosine and carnosine supplement with simvastatin were the most effective in lowering this comprehensive lipid index. Dietary carnosine supplementation resulted also in anti-inflammatory effects, as demonstrated by immunohistochemical analyses. Besides, the good safety profile of carnosine in terms of its effect on liver and kidney functions was also confirmed. CONCLUSIONS: The use of carnosine supplements in preventing and/or treatment of metabolic disorders requires further investigations into the mechanisms of action and potential interactions with conventional therapy.
Subject(s)
Carnosine , Dyslipidemias , Rats , Male , Animals , Hypolipidemic Agents/pharmacology , Diet, High-Fat , Carnosine/pharmacology , Carnosine/therapeutic use , Rats, Wistar , Triglycerides , Dietary Supplements , Liver/metabolism , Dyslipidemias/metabolism , Simvastatin/pharmacologyABSTRACT
BACKGROUND AND OBJECTIVES: Serenoa repens extracts (SrE) have been used for centuries in the treatment of benign prostatic hyperplasia (BPH). According to recommendations that each product should be examined separately, including its tolerability and toxicity, we conducted this study in order to broaden the current cognition about tolerability and toxicity of SrE, in particular of German brand ProstamolunoR. MATERIALS AND METHODS: Twenty-four adult male Wistar rats were randomly distributed into 4 groups of 6 animals. The first control group (O) received water (1 ml/kgBW) and second control group (OO) received olive oil (1 ml/kgb.w.) every day for 30 days. The third and fourth group of rats (SR5 and SR10) were treated with SrE (150 and 300 mg/kgb.w. daily) dissolved in olive oil. Tolerability and toxicity of SrE were estimated on the basis of daily monitoring of behavior, body weight gain (BWG), relative weight of liver, left kidney, prostate and left testis, and values of general biochemical parameters. Total liver proteins (TLP) and glutathione content in hepatocyte suspension were also determined. RESULTS: BWG was significantly unchanged in SR5 and SR10 compared to both controls in all intervals of measurement and at the end of treatment (p > 0.05). LW/BW ratio was significantly higher in SR10 compared with O (p < 0.01). Creatinine and potassium were significantly higher in SR5 compared to O (p < 0.05), but in SR10 were significantly higher compared to both control groups (p < 0.01). TLP content was significantly higher in SR5 compared to OO (p < 0.01). The content of glutathione in homogeneous suspension of hepatocytes didn't alter significantly. CONCLUSIONS: Obtained results have expanded the current state of knowledge about the tolerability and toxicity of SrE, in particular of Prostamol-unoR. For the adoption of a more precise conclusion about its tolerability and toxicity, it should be excluded possible limiting factors that we identified in this study.
Subject(s)
Serenoa/toxicity , Algorithms , Animals , Creatinine/blood , Electrolytes/blood , Glutathione/metabolism , Liver/drug effects , Liver Function Tests , Male , Organ Size/drug effects , Plant Extracts/toxicity , Rats , Rats, Wistar , Serenoa/chemistry , Urea/blood , Weight Gain/drug effectsABSTRACT
OBJECTIVE: Plants and plant extracts are of great scientific interest due to the chemical diversity and pharmacological properties of present bioactive molecules. The Geranium L. species are widely used in ethnomedicine. In the current study, the total phenolic and tannin content, antioxidant and antimicrobial activity of methanol extracts of eight Geranium species were investigated. MATERIALS AND METHODS: The total phenolic and tannin content were determined by the FC method. Antioxidant capacity was evaluated in FRAP, DPPH, and biochemical assays, while antimicrobial activity was examined using the broth microdilution method. RESULTS: The high total phenolic (170.64-636.32 mg GAE/g dry extract) and tannin content (37.80-414.02 mg GAE/g DE), along with significant total antioxidant (FRAP values 1.13-8.80 mmol Fe2+/g) and DPPH radical scavenging activity (SC50 values 4.24-34.52 µg/mL) were observed. The prominent antioxidant capacity was confirmed in biochemical assays (OS values -1.47 - -13.02). The extracts exhibited significant antimicrobial activity against ATTC strains (MICs dominantly in the range of 12.5-200 µg/mL) as well as against clinical isolates of E. coli (MICs mostly 50 and 100 µg/mL). The pronounced antioxidant and antimicrobial activity can be due to the high phenolic content, particularly due to the presence of hydrolyzable tannins. CONCLUSIONS: Based on the high content of polyphenols, pronounced antioxidant and antimicrobial activities, the examined extracts are promising natural antioxidant and antimicrobial agents with the potential medicinal purpose and use as a functional food.
Subject(s)
Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Geranium/chemistry , Plant Extracts/pharmacology , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/isolation & purification , Antioxidants/administration & dosage , Antioxidants/isolation & purification , Dose-Response Relationship, Drug , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/isolation & purification , Free Radical Scavengers/pharmacology , Humans , Microbial Sensitivity Tests , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Polyphenols/administration & dosage , Polyphenols/isolation & purification , Polyphenols/pharmacology , Tannins/administration & dosage , Tannins/isolation & purification , Tannins/pharmacologyABSTRACT
Patients with mesial temporal lobe epilepsy (mTLE) show structural and functional abnormalities in hippocampus and surrounding mesial temporal structures. Brain signal complexity appears to be a marker of functional integrity or capacity. We examined complexity in 8 patients with intracranial hippocampal electrodes during performance of memory tasks (scene encoding and recognition) known to be sensitive to mesial temporal integrity. Our patients were shown to have right mesial temporal seizure onsets, permitting us to evaluate both epileptogenic (right) and healthy (left) hippocampi. Using multiscale entropy (MSE) as a measure of complexity, we found that iEEG from the epileptogenic hippocampus showed less complexity than iEEG from the healthy hippocampus. This difference was reliable for encoding but not for recognition. Our results indicate that both functional integrity and cognitive demands influence hippocampal signal complexity.
Subject(s)
Cognition/physiology , Epilepsy, Temporal Lobe/pathology , Functional Laterality/physiology , Hippocampus/physiopathology , Memory/physiology , Adult , Electroencephalography/methods , Entropy , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Temporal Lobe/physiopathologyABSTRACT
Early in life, brain development carries with it a large number of structural changes that impact the functional interactions of distributed neuronal networks. Such changes enhance information processing capacity, moving the brain from a deterministic system to one that is more stochastic. The evidence from empirical studies with EEG and functional MRI suggests that this stochastic property is a result of an increased number of possible functional network configurations for a given situation. This is captured in the variability of endogenous and evoked responses or "brain noise ". In empirical data from infants and children, brain noise increases with maturation and correlates positively with stable behavior and accuracy. The noise increase is best explained through increased noise from network level interactions with a concomitant decrease of local noise. In old adults, brain noise continues to change, although the pattern of changes is not as global as in early development. The relation between high brain noise and stable behavior is maintained, but the relationships differ by region, suggesting changes in local dynamics that then impact potential network configurations. These data, when considered in concert with our extant modeling work, suggest that maturational changes in brain noise represent the enhancement offunctional network potential--the brain's dynamic repertoire.
Subject(s)
Brain Mapping , Brain/growth & development , Models, Neurological , Noise , Nonlinear Dynamics , Acoustic Stimulation/methods , Adolescent , Adult , Age Factors , Animals , Brain/blood supply , Child , Child Development , Electroencephalography/methods , Humans , Infant , Magnetic Resonance Imaging/methods , Nerve Net/blood supply , Nerve Net/physiology , Photic Stimulation/methods , Time FactorsABSTRACT
Quantitative analyses and investigation of antioxidant activity of herb and dry ethanolic extracts of five species from Ericaceae family (Arbutus unedo L., Bruckentalia spiculifolia Rchb., Calluna vulgaris Salisb., Erica arborea L. and Erica carnea L.) were performed. Total polyphenols, tannins and flavonoids were determined spectrophotometrically and arbutin content was measured both spectrophotometrically and by HPLC coupled with DAD detection. Antioxidative properites of the ethanolic extracts were tested by means of FRAP (total antioxidant capacity), lipid peroxidation and DPPH free radical scavenging activity. A significant amount of arbutin was detected only in Arbutus unedo. All samples investigated showed excellent antioxidant activity. The best inhibition of lipid peroxidation has been shown by Bruckentalia spiculifolia herb extract (62.5 microg/ml; more than 95%), which contained the highest amount of flavonoids (11.79%). The highest scavenging activity was obtained with leave extract of Arbutus unedo (IC50 = 7.14 microg/ml). The leaves of A. unedo contained a small amount of flavonoids but high content of non-tannins polyphenols.
Subject(s)
Antioxidants/analysis , Arbutin/analysis , Ericaceae/chemistry , Antioxidants/pharmacology , Arbutin/pharmacology , Biphenyl Compounds , Chromatography, High Pressure Liquid , Ferric Compounds/chemistry , Flavonoids/analysis , Flavonoids/pharmacology , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Hydroquinones/chemistry , Lipid Peroxidation/drug effects , Oxidants/chemistry , Phenols/analysis , Phenols/pharmacology , Picrates , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polyphenols , Spectrophotometry, Ultraviolet , Tannins/analysis , Tannins/chemistryABSTRACT
Finasteride is a potent drug which has been prescribed for the management of benign prostatic hyperplasia (BPH) for more than 20 years. Recent studies indicate that finasteride, as 5alpha-reductase inhibitor, can influence some central effects such as analgesia, neurosteroidogeneses and behavior. The purpose of this study was to investigate the analgesic effect of finasteride, to determine whether finasteride interact with morphine analgesia in tail-flick test and to examine the anti-inflammatory effect of this drug. Adult male Wistar rats (280-330 g) were used for the both of experiments. Tests were assessed on groups of 6 animals. The first control group (O) received water (1 ml/kg, p.o.), the second control group (OO) received the vehicle (olive oil, 1 ml/kg, p.o.) and the third group (F) received finasteride (0.5 mg/kg, p.o.) suspended in olive oil, every morning for 30 days. After 30 days of treatment, tail-flick test and formalin-induced foot paw edema test were performed. Finasteride increased the average latency in seconds in comparison to both controls (10.06 vs. 9.16 and 8.66 s). It was 9.83% higher depression of pain in group F in comparison to O and 16.17% in comparison to OO, but the anti-nociceptive effect of finasteride at applied dose didn't significantly differ compared to both controls (p > 0.05). Chronic pre-treatment with finasteride didn't interact with analgesic effect of morphine compared to O (p > 0.05), but compared to OO finasteride fastened, increased and prolonged the analgesic effect of morphine at all measuring intervals, achiving statistical significance in 60 min (p < 0.01). Finasteride also exhibited significant anti-inflammatory action (p < 0.05) in comparison to OO, but It was not significantly different from the control O. Finasteride didn't exert analgesic action, it increased morphine antinociception and showed chronic anti-inflammatory effect to some extent. This might be a useful contribution to highlight the pathogenesis of BPH. There is the need for further studies in order to confirm these results with more details.
Subject(s)
5-alpha Reductase Inhibitors , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Enzyme Inhibitors/pharmacology , Finasteride/pharmacology , Analgesics/administration & dosage , Analgesics/therapeutic use , Analgesics, Opioid/pharmacology , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Edema/drug therapy , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/therapeutic use , Finasteride/administration & dosage , Finasteride/therapeutic use , Male , Morphine/pharmacology , Pain Measurement , Pain Threshold/drug effects , Rats , Rats, WistarABSTRACT
UNLABELLED: In order to elucidate the role of insulin and glucagon during strenuous exercise (100 m/min, slope 10-12 degrees), we have determined the rates of production (Ra), utilization (Rd), and metabolic clearance (M) of glucose in normal dogs before pancreatectomy and 2 wk after total pancreatectomy (a) when they were being maintained on constant intraportal basal insulin infusion, (245 muU/kg-min) and (b) when insulin supply had been withheld before and during exercise. Such an intense exercise induced in normal dogs a prompt decrease in mean immunoreactive serum insulin (IRI) from 20 +/- 3 to 11 +/- 2 muU/ml. In depancreatized insulin-infused dogs serum IRI during rest and exercise was between 14 +/- 1 and 12 +/- 2 muU/ml. In the third group, after cessation of insulin infusion, IRI decreased by 76% (from 17 +/- 5 to 4 +/- 1) and did not decrease futher during exercise. During exercise, serum immunoreactive glucagon (IRG) increased threefold in normal dogs. In depancreatized dogs serum IRG was the same as in normal resting dogs (indicating a nonpancreatic source of the hormone) but it did not increase during exercise. In normal dogs exercise induced proportional increases in Ra, Rd, and M (threefold) and normoglycemia was maintained. Changes in glucose turnover in depancreatized insulin-infused dogs were similar to those seen in normal dogs suggesting that a decrease in insulin secretion and a rise in IRG are not essential to prevent hypoglycemia in diabetic dogs. With the cessation of insulin infusion in resting depancreatized dogs, Ra increased, M decreased, and hyperglycemia ensued. During exercise, Ra continued to rise, but M did not increase significantly. CONCLUSIONS: (a) Regulation of glucose production by liver during exercise is multifactorial. A decrease in IRI and an increase in IRG are not the only factors which can promote delivery of glucose to the peripheral tissues. The insulin glucagon molar ratio was found not to be an essential metabolic functional unit in regulating glucose metabolism during exercise. (b) It is hypothesized that increases in blood flow and capillary surface area can lead to an increase in the amount of insulin delivered to the muscle even when serum levels of IRI are reduced during exercies. It is suggested that small, but adequate amounts of insulin (as found in normal and depancreatized insulin-infused dogs) are essential in regulating glucose uptake in the working muscle. (c) Since totally depancreatized dogs had normal serum levels of IRG (originating presumably from the gastrointestinal tract), the question of essentiality of basal glucagon activity in glucose homeostasis during exercise could not be resolved by these experiments. It appears, however, that regulation of secretion of nonpancreatic glucagon differs from that of pancreatic glucagon.
Subject(s)
Blood Glucose/metabolism , Glucagon/physiology , Insulin/physiology , Animals , Antigens , Dogs , Glucose/metabolism , Homeostasis , Insulin/metabolism , Male , Muscles/metabolism , Pancreatectomy , RestABSTRACT
The mouse has emerged as a major experimental model system for examining the functional properties of the mammalian CNS; both during development and following CNS injury. Histologic procedures currently used to determine the relative position of structures within the CNS are presently limited in their ability to take full advantage of this system for surgical and morphometric procedures. We present here the first three-dimensional interactive digital atlas of the murine brain and skull for two genetically important strains of mice; 129S1/SvImJ and C57Bl/6J. The final resolution of these digital atlases is 54 micro m(3). These representations of the murine brain and skull, in conjunction with our development of a new, more dynamic master coordinate system, provide improved accuracy with respect to targeting CNS structures during surgery compared with previous systems. The interactive three-dimensional nature of these atlases also provide users with stereotactic information necessary to perform accurate "off-axis" surgical procedures, as is commonly required for experiments such as in vivo micro-electroporation. In addition, three-dimensional analysis of the brain and skull shape in C57Bl, 129Sv, CD1, and additional murine strains, suggests that a stereotactic coordinate system based upon the lambda and rostral confluence of the sinuses at the sagittal midline, provides improved accuracy compared with the traditional lambda-bregma landmark system. These findings demonstrate the utility of developing highly accurate and robust three-dimensional representations of the murine brain and skull, in which experimental outputs can be directly compared using a unified coordinate system. The aim of these studies is to enhance comparative morphometric analyses and stereotactic surgical procedures in mice.
Subject(s)
Head/anatomy & histology , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Animals , Mice , Mice, Inbred C57BL , Stereotaxic Techniques , Tomography, X-Ray Computed/methodsABSTRACT
The effect of the methanolic extract of the underground parts of Epimedium alpinum L. (MEEA) on the immune response to Keyhole Limpet Hemocyanine (KLH) or alloantigens in vivo was studied in AO rats. Immunization of experimental animals with KLH or allogeneic lymphocytes together with MEEA was followed by an increase in cellularity of draining lymph nodes (LN) and enhanced proliferation of LN lymphocytes after their restimulation with specific antigens in vitro, compared to control rats immunized without MEEA. These effects correlated with an increase in relative values of B, MHC class II+, CD25+ and CD71+ cells, whereas percentages of T cells and both subsets of T cells (CD4+ and CD8+) were not significantly altered. As a consequence of higher LN cellularity, total numbers of all cell subsets in the MEEA-treated group of rats were significantly increased, compared to the corresponding control. The addition of MEEA together with KLH in vitro to LN lymphocytes of rats immunized with KLH or KLH and MEEA in vivo was manifested by significant increase (0.1 microg/ml of MEEA) and decrease (50 microg/ml and 100 microg/ml of MEEA) of cell proliferation, respectively. However, when LN lymphocytes from rats, immunized in vivo with KLH and MEEA, were stimulated in vitro with MEEA together with an anti-alphabeta T cell receptor monoclonal antibody (R73), their proliferation was siginificantly inhibited. Taken together, obtained results suggest that MEEA possesses immunostimulatory activity in vivo, but some components from the extract exert immunosuppressive effects in vitro on previously in vivo activated T cells.
Subject(s)
Adjuvants, Immunologic/pharmacology , Epimedium/chemistry , Immunity/drug effects , Animals , Cell Proliferation/drug effects , Female , Flow Cytometry , Hemocyanins/immunology , Immunization , Lymphocytes/immunology , Methanol , Phenotype , Plant Extracts/pharmacology , Rats , Solvents , T-Lymphocytes/drug effectsABSTRACT
The antioxidative potential of Achillea alexandri-regis has been studied by measuring the influence of herb extracts on hydroxyl and superoxide radicals' quantity in different in vitro systems. The ethyl acetate extract exhibited hydroxyl radical scavenging activity in all tested biological system (liver homogenate, hemolyzed blood, serum and postmitochondrial liver fraction), whereas butanol extract reduced hydroxyl radicals significantly only in the postmitochondrial liver fraction. Both extracts showed superoxide radical scavenging effect only in hemolyzed blood.
Subject(s)
Achillea , Antioxidants/pharmacology , Free Radical Scavengers/pharmacology , Phytotherapy , Plant Extracts/pharmacology , Animals , Antioxidants/chemistry , Free Radical Scavengers/chemistry , Hydroxyl Radical/chemistry , Lipid Peroxidation/drug effects , Mitochondria, Liver/drug effects , Plant Extracts/chemistry , Rats , Superoxides/chemistryABSTRACT
The cytotoxicity and antioxidant properties of herb extracts of Achillea alexandri-regis were studied. Combined chloroform and ethylacetate extracts exhibited a pronounced cytotoxic effect against HeLa cancer cells (IC50 = 25.92 +/- 4.96 microg/ml), and lower cytotoxicity against K562 leukemia cells (IC50 = 48.59 +/- 18.31 microg/ml). The methanol extract was found to be a moderately cytotoxic in vitro agent against HeLa and K562 cells. No suppressive activity was detected on non-malignant peripheral blood mononuclear cells (PBMC). The antioxidant activity of the methanol extract was assessed by DPPH radical scavenging. The methanol extract of A. alexandri-regis showed concentration dependent DPPH radical scavenging activity with IC50 = 36.14 +/- 0.05 microg/ml.
Subject(s)
Achillea/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Biphenyl Compounds , Free Radical Scavengers/pharmacology , HeLa Cells , Humans , Monocytes/drug effects , Picrates/pharmacologyABSTRACT
We have observed both hyperglucagonemia and hypoinsulinemia in adrenalectomized (Adx) dogs. To determine whether these hormonal alterations are related to changes in distribution of islet hormones in the pancreas, we examined the concentration and total mass of insulin, glucagon, and somatostatin in the head, body, and tail of the pancreas by immunoassay and immunocytochemistry. We studied 6 normal dogs, 5 Adx dogs deprived of cortisol for 24 h (Adx I) and 5 for 48-72 h (Adx II). In normal dogs, single and double immunocytochemical staining showed that, in contrast to some other species, B (insulin) cells are mostly in the central region of islet, whereas A (glucagon) and D (somatostatin) cells are distributed randomly. This topographic distribution was not altered by adrenalectomy. In normal dogs, insulin concentration (micrograms per g) and total mass (micrograms) were higher in the tail (174 +/- 22, 2001 +/- 396) and body (165 +/- 22, 2850 +/- 600) than in the head (91 +/- 17, 668 +/- 156) of pancreas. Glucagon concentration (micrograms per g) and total mass (micrograms) were 17 +/- 2, 178 +/- 17 in the tail; 9.5 +/- 2, 158 +/- 32 in the body, and negligible (0.78 +/- 0.32, 7 +/- 3) in the head, whereas somatostatin concentration (micrograms per g) and total mass (micrograms) were 0.58 +/- 0.26, 4.20 +/- 1.5 in the T, 0.23 +/- 0.10, 3.9 +/- 1.6 in the B, and 0.22 +/- 0.05, 1.8 +/- 0.6 in the H. The striking finding was that adrenalectomy caused large increases in somatostatin in all three regions of pancreas in both Adx I and Adx II. The total mass of somatostatin in Adx I and Adx II increased 4-fold in the tail (P less than 0.02-0.005), 5-fold in the body (P less than 0.01-0.001), and 7-9-fold in the head (P less than 0.05-0.005) and concentration increased 6-fold in the body (P less than 0.005) and 7- to 8-fold in the head (P less than 0.01-0.001). There were no significant changes in the content of insulin and glucagon after adrenalectomy. Plasma concentration of glucagon increased by 50% in Adx I (P less than 0.005) and 70% in Adx II (P less than 0.02), insulin decreased by 39% (P less than 0.005), 23% (NS), respectively, and somatostatin increased by 258% (P less than 0.001) in Adx II. Thus the adrenal glands appear to play an important role in regulation of the content of somatostatin in pancreatic islets.
Subject(s)
Glucagon/metabolism , Insulin/metabolism , Islets of Langerhans/metabolism , Somatostatin/metabolism , Adrenalectomy , Animals , Dogs , Hydrocortisone/pharmacology , Tissue DistributionABSTRACT
To characterize the glucagon released in response to epineephrine in depancreatized dogs, plasma samples before and during epinephrine infusion were subjected to molecular-sieve chromatography on Bio-Gel P-30 columns. The chromatographic profile for extrapancreatic immunoreactive glucagon (eIRG) revealed two glucagon moieties of molecular weight 9,000 to 12,000. GLI of this molecular weight was released in response to epinephrine only under conditions of prevailing hyperglycemia. To determine if glucagon's participation in epinephrine-induced hepatic glucose overproduction in diabetes was dependent upon the degree of metabolic control, six conscious depancreatized dogs were infused with epinephrine or epinphrine plus somatostatin, under conditions of prevailing hyperglycemia or normoglycemia. Under normoglycemic conditions, epinephrine stimulated eIRG release, but there was a similar rise in hepatic glucose production (Ra) with or without glucagon suppression by somatostatin. Under hyperglycemic conditions, epinephrine stimulated eIRG and GLI release, and the rise in Ra was significantly greater with epinephrine than with epinephrine plus somatostatin infusion. Thus, under conditions of good metabolic control, epinephrine increased hepatic glucose production independently of glucagon, whereas with poor metabolic control, glucagon contributed to hepatic overproduction of glucose.