bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Oxidative Stress in Rat Liver and Pancreas during Progression of Streptozotocin-Induced Diabetes
Authors: Kakkar Rakesh , Mantha Subrahmanyam V. , Radhi Jasim , Prasad Kailash , Kalra Jawahar 
Published: August 2015

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. There are many reports indicating the changes in parameters of oxidative stress in diabetes mellitus. In this study we aimed to identify whether oxidative stress occurs in the liver and pancreas in the initial stages of development of diabetes.
2. We therefore investigated the lipid peroxide level (thiobarbituric acid-reactive substances, TBARS) and activities of antioxidant enzymes [superoxide dismutase (SOD), catalase and glutathione peroxidase] in liver and pancreas of control and streptozotocin-induced diabetic rats at various stages of development of diabetes.
3. Male Sprague—Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups consisting of six rats each. Rats in these subgroups were studied at weekly intervals (0 to 6 weeks). Plasma glucose levels, TBARS levels and activities of antioxidant enzymes were measured in liver and pancreas at various time intervals.
4. There was a significant (P &lt; 0.05) and progressive increase in TBARS levels of liver and pancreas in the diabetic group. Total SOD and Cu—Zn-SOD activity increased (P &lt; 0.05) with progression of diabetes while Mn-SOD activity showed no significant change in either tissue. Catalase and glutathione peroxidase activities increased significantly (P &lt; 0.05) in liver and pancreas.
5. Immunohistochemical study of pancreatic islet revealed a decrease in the expression of insulin with progression of diabetes. However, glucagon and somatostatin showed an increase in immunoreactivity and a difference in their distribution pattern.
6. The findings of the present study suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively. In conclusion, the structural damage to these tissues or complications of diabetes mellitus may be due to oxidative stress.
Effect of Long-Term Octreotide and Isosorbide Dinitrate on Haemodynamics in Rats with Portal Vein Stenosis
Authors: Lin Han-Chieh , Huang Yi-Tsau , Cheng Yuh-Ren , Hou Ming-Chih , Lee Fa-Yauh , Chang Full-Young , Tsai Yang-Te , Lee Shou-Dong 
Published: August 2015

1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis.
2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 μg/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique.
3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatment was significantly lower than in rats receiving octreotide alone.
4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.
Concentration-Dependent Stimulation of Intestinal Phase III of Migrating Motor Complex by Circulating Serotonin in Humans
Authors: Lördal Mikael , Wallén Håkan , Hjemdahl Paul , Beck Olof , Hellström Per M. 
Published: August 2015

1. The influence of circulating 5-hydroxytryptamine (serotonin) on small intestinal motility was investigated in healthy volunteers.
2. Small intestinal motility was studied by means of a constantly perfused multi-channel manometry tube, connected to a computer system.
3. Intravenous infusions of either 5-hydroxytryptamine at increasing doses or saline were given over a period of 4 h.
4. 5-Hydroxytryptamine infusion dose-dependently increased plasma 5-hydroxytryptamine from approximately 2 to 10 and 25 nmol/l respectively, as well as urinary excretions of 5-hydroxytryptamine and 5-hydroxyindole acetic acid, a major 5-hydroxytryptamine metabolite.
5. The number of phase III of the migrating motor complex originating in the small intestine was dose-dependently increased by 5-hydroxytryptamine, and found to correlate to the plasma concentration of 5-hydroxytryptamine. The fraction of phase III also increased at the expense of phase II activity. In addition, 5-hydroxytryptamine increased the motility index, propagation velocity of phase III activity and the amplitude of contractions during phase III.
6. Whereas the low dose of 5-hydroxytryptamine (15 nmol · min−1 · kg−1) had no haemodynamic effects, an increase in heart rate by approximately 20 beats/min, without change in blood pressure, was observed at the higher dose (60 nmol · min−1 · kg−1). Respiratory parameters did not change during infusion of 5-hydroxytryptamine at either dose.
7. In conclusion, elevation of circulating 5-hydroxytryptamine by intravenous infusion results in more frequent and faster propagating migrating motor complexes in the human small intestine during the interdigestive period.
Regional Differences in Protein Carboxymethylation in Post-Mortem Human Brain
Authors: Goggins Michael , Scott John M. , Weir Donald G. 
Published: August 2015

1. The aim of this study was to determine the pattern of protein carboxymethylation in different regions of the human brain.
2. The availability of protein methylation sites was determined by measurement of the incorporation of methyl-3H groups into proteins isolated from postmortem brain tissue. The stability of protein carboxymethylation in post-mortem brain was determined by sampling post-mortem pig and human brain tissue at intervals during the first 24 h after death. This method has previously been used to demonstrate that decreased protein carboxymethylation occurred in post-mortem pig brain when methionine synthase was inhibited.
3. There were no significant differences in the protein carboxymethyltransferase activity in samples of pig brain obtained at the time of death compared with that obtained when the same tissue was maintained at room temperature for up to 24 h after death. Similarly, there were no significant differences in the protein carboxymethyltransferase activity in samples isolated from human brain 12 h after death compared with that obtained from the same human brain tissue maintained at room temperature for up to 24 h after death. These results suggest that the level of carboxymethylation of proteins from human post-mortem brain obtained within 24 h of death is not significantly different to the level present at the time of death. To characterize the distribution of protein carboxymethylation in human brain, nine regions of post-mortem brain were sampled from 16 human subjects. Protein carboxymethyltransferase activity was lowest in the cerebellum (P &lt; 0.05) and highest in cortical white matter compared with other regions of the brain (P &lt; 0.05). No significant differences in protein carboxymethyltransferase activity were noted between other regions of the cortex or the subcortical regions.
4. In human cortical white matter there are more available sites for protein carboxymethylation than other brain regions. This may explain the greater sensitivity of white matter to the adverse consequences of hypomethylation associated with vitamin B12 deficiency. Post-mortem brain tissue can serve as a tool for the study of physiological or pathological factors which influence human brain protein methylation in vivo.
Clinical and therapeutic significance of the Na+,K+ pump*
Authors: CLAUSEN Torben 
Published: August 2015

1.The Na+,K+-ATPase or Na+,K+-pump, mediating the active transport of Na+ and K+, which was first identified 40 years ago, is a central target for acute and long-term regulation, as well as for therapeutic intervention. Acute stimulation of the Na+,K+-pump in skeletal muscle by insulin, catecholamines, β2-agonists or theophylline increases the intracellular uptake of K+ and accounts for the hypokalaemia elicited by these agents. Conversely, digitalis intoxication elicits hyperkalaemia via acute inhibition of the Na+,K+-pump.
2.Simple and accurate methods have been developed for the quantification of the total concentration of Na+,K+-pumps in small (0.5–5 mg) fresh or frozen biopsies of human skeletal muscle, myocardium or other tissues. This has allowed the identification of several long-term regulatory changes in the concentration of this transport system in human tissues. In skeletal muscle, upregulation is induced by training, thyroid hormones or glucocorticoids. Downregulation is seen in hypothyroidism, cardiac insufficiency, myotonic dystrophy, McArdle disease, K+ deficiency and after muscle inactivity.
3.Since the skeletal muscles contain one of the major pools of Na+,K+-pumps, these changes are important for the ability to counterregulate the hyperkalaemia elicited by exercise or the ingestion of K+. Moreover, downregulation or inhibition of the Na+,K+-pumps in skeletal muscle interferes with contractile performance. Since digitalis glycosides bind to the Na+,K+-pump, the muscles constitute a large distribution volume for these agents and are therefore an important determinant for their plasma level.
4.In cardiac insufficiency, the decrease in the concentration of Na+,K+-pumps in the myocardium is over a wide range correlated to the concomitant reduction in ejection fraction. The regulatory and pathophysiological changes in the activity and concentration of Na+,K+-pumps are important for the contractile function of skeletal muscle and heart as well as for K+ homoeostasis and the response to digitalization.
Renal haemodynamics, sodium and water reabsorption during continuous intravenous infusion of recombinant interleukin-2
Authors: GEERTSEN Poul F. , MAASE Hans VON DER , OLSEN Niels Vidiendal , FOGH-ANDERSEN Niels , NIELSEN Steen Levin , LEYSSAC Paul P. 
Published: August 2015

1.Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma.
2.Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18×106 i.u.·24 h-1·m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow.
3.Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P = 0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P = 0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P = 0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1α increased by 98% (P = 0.022) and 175% (P = 0.022) respectively.
4.The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.
Possible interaction between exposure to environmental tobacco smoke and therapy in children with asthma
Authors: DUBUS Jean-Christophe , ODDOZE Christiane , BADIER Monique , GUILLOT Chantal , BRUGUEROLLE Bernard 
Published: August 2015

1.The aim of the study was to determine the carbachol and albuterol responsiveness in treated and untreated asthmatic and allergic children exposed to environmental tobacco smoke assessed by urinary cotinine measurements.
2.Forty-six asthmatic and allergic children with normal spirometric values were recruited. The doubling dose, concentration of carbachol producing a 2-fold increase in specific airway resistance (SRaw) was determined and 200 ;μg of albuterol were administered via a Volumatic® spacer. The percentage of bronchodilatation was defined as the difference between the largest obtained SRaw and the post-β2 SRaw divided by the largest SRaw. Data were compared by a Mann–Whitney U-test.
3.The 23 children with a high urinary cotinine, compared with the 23 children without urinary cotinine, had a decreased doubling dose (108.2±14.7 ;μg versus 160.9±19.5 ;μg; P = 0.04) and an increased percentage of bronchodilatation (74.8±1.4% versus 68.8±1.8%; P = 0.03). A prophylactic anti-inflammatory treatment induced a weaker bronchial reactivity to carbachol and a slightly greater bronchodilatation in children exposed to environmental tobacco smoke.
4.Environmental tobacco smoke increases bronchial reactivity in asthmatic and allergic children. This effect might be reduced by anti-inflammatory therapy. The bronchodilator response may be enhanced in exposed children and may be caused by one or several direct interactions between tobacco smoke compounds and albuterol.
A method for examining differential mRNA expression along the crypt–villus axis of the human small intestine
Authors: CHUA Eddy , WANG Qiong , O'TOOLE Paul , LOMBARD Martin 
Published: August 2015

1.The aim of this study was to devise a method of segregating crypt and villus cell subpopulations from endoscopic human small intestinal biopsies which might be used to examine changes associated with functional differentiation at the molecular level.
2.Routine endoscopic biopsies from the human small intestine were subjected to a modified protocol of mechanical disruption and chelation to yield subpopulations of different cell types. The purity and character of the cell populations isolated was assessed by measuring enzyme activity and thymidine incorporation and by histology. A guanidinium isothiocyanate method was adapted for small samples to extract RNA from the isolated subpopulations, and probes for RNA with a known predilection for crypt and villus cells were used to further investigate the application and usefulness of the technique.
3.Sequential histological examination during the segregation protocol demonstrated that different cell types were removed serially from the biopsy samples. Cell-type enrichment of the segregated subpopulations was demonstrated by differential alkaline phosphatase activity and by differences in thymidine incorporation in the samples isolated. Sufficient quantities of RNA could be extracted from the segregated subpopulations for Northern blot analysis and the differential expression of mRNA for sucrase-isomaltase and transferrin receptor was demonstrated in the villus and crypt subpopulations respectively.
4.Messenger RNA can be successfully extracted from different cell types segregated from routine human endoscopic small intestinal biopsies. This technique should prove useful for investigating the mechanisms regulating the functional differentiation of epithelial cells in the small intestine and the regulatory mechanisms governing absorption of macromolecules.
Rat hepatic stellate cell expression of α2-macroglobulin is a feature of cellular activation: implications for matrix remodelling in hepatic fibrosis
Authors: KAWSER C. A. , IREDALE J. P. , WINWOOD P. J. , ARTHUR M. J. P. 
Published: August 2015

1.Hepatic stellate cells are key mediators of hepatic fibrosis. We have studied hepatic stellate cell expression of the collagenase and general protease inhibitor α2-macroglobulin after activation in tissue culture and in response to certain cytokines.
2.Hepatic stellate cells isolated by Pronase–collagenase digestion were activated by culture on uncoated plastic. By Northern analysis hepatic stellate cells undergoing activation (5 days) expressed α2-macroglobulin mRNA and α2-macroglobulin could be immunolocalized to hepatic stellate cells from 5 to 15 days of culture.
3.By ELISA of cell culture supernatants hepatic stellate cell secretion of α2-macroglobulin was found to increase from 2.78±1.13 ;ng·ml-1·μg-1 DNA per 24 ;h at 5 days of culture (n = 8) to 13.55±4.64 ;ng·ml-1·μg-1 DNA per 24 ;h at 15 days of culture (n = 7). Stimulation of hepatic stellate cells with interleukin-6 at 5 days caused a significant increase in α2-macroglobulin expression as did exposure to Kupffer-cell conditioned medium. However, exposure of hepatic stellate cells to interleukin-1, transforming growth factor-β1 and tumour necrosis factor-α had no significant effect.
4.During profibrotic liver injury plasma α2-macroglobulin levels were found to increase to between 850% and 250% of the control value (100%) after bile duct ligation (72 ;h to 13 days respectively), and to 1166% and 1106% of the control value during progressive CCl4-induced fibrosis (24 ;h to 4 weeks respectively).
5.These data suggest that hepatic stellate cells are a potential source of the potent protease inhibitor α2-macroglobulin, expression of which may inhibit matrix remodelling during progressive fibrosis.
Proteasome blockers inhibit protein breakdown in skeletal muscle after burn injury in rats
Authors: FANG Cheng-Hui , WANG Jing Jing , HOBLER Scott , LI Bing Guo , FISCHER Josef E. , HASSELGREN Per-Olof 
Published: August 2015

1.Burn injury stimulates ubiquitin-dependent protein breakdown in skeletal muscle. The 20S proteasome is the proteolytic core of the 26S proteasome that degrades ubiquitin conjugates. We examined the effects of the proteasome inhibitors N-acetyl-l-leucinyl-L-leucinal-l-norleucinal (LLnL), lactacystin and β-lactone on protein breakdown in muscles from burned rats.
2.A full-thickness burn of 30% total body surface area was inflicted on the back of rats. Control rats underwent a sham procedure. After 24 ;h, extensor digitorum longus muscles were incubated in the absence or presence of 20S proteasome blocker and protein turnover rates and ubiquitin mRNA levels were determined.
3.LLnL resulted in a dose- and time-dependent inhibition of total protein breakdown in incubated muscles from burned rats. Lactacystin and β-lactone blocked both total and myofibrillar muscle protein breakdown. In addition to inhibiting protein breakdown, LLnL increased ubiquitin mRNA levels, possibly reflecting inhibited proteasome-associated RNase activity.
4.Inhibited muscle protein breakdown caused by LLnL, lactacystin and β-lactone supports the concept that the ubiquitin–proteasome pathway plays a central role in burn-induced muscle proteolysis. Because the proteasome has multiple important functions in the cell, in addition to regulating general protein breakdown, further studies are needed to test the role of proteasome blockers in the treatment or prevention of muscle catabolism.
A central γ-aminobutyric acid mechanism in cardiac vagal control in man revealed by studies with intravenous midazolam
Authors: FARMER Matthew R. , VAILE Julian C. , OSMAN Faisal , ROSS Hamish F. , TOWNEND Jonathan N. , COOTE John H. 
Published: August 2015

1.Animal studies show that cardiac vagal tone can be modified by γ-aminobutyric acid neurons acting at several sites in the central nervous system. The present study has attempted to determine whether similar control exists in humans by using midazolam, a benzodiazepine. Benzodiazepines exert their main actions on the central nervous system by interacting co-operatively at the γ-aminobutyric acid receptor.
2.Twenty patients took part in the study before undergoing cardiac catheterization. After resting for 20 ;min in a semi-supine position on a couch, ECG, blood pressure and respiration were recorded for 5-min periods with either controlled (fixed) or free respiration. During this time a baroreceptor sensitivity test was conducted.
3.Doses of 1 ;mg and 5 ;mg of midazolam were administered intravenously.
4.Five-minute segments of data, before and after midazolam, were subjected to power spectral and time-domain analysis.
5.Midazolam caused a decrease in the high-frequency and an increase in the low-frequency components of the power spectral density plot, and in addition reduced the mean R–R interval and R–R variability expressed as the interquartile difference, and pNN50. There were no significant changes in the sensitivity of the baroreflex or in the systolic, diastolic and average blood pressures.
6.This decrease in variability of heart period, particularly at a controlled respiratory frequency, strongly suggests that cardiac vagal tone in man can be regulated by γ-aminobutyric acid neurons.
Influences of carvedilol treatment on the effects of acetylcholine on regional haemodynamics in the spontaneously hypertensive rat
Authors: GRANSTAM Sven-Olof , FELLSTRÖM Bengt , LIND Lars 
Published: August 2015

1.Investigations that assess cardiac autonomic function include non-linear techniques such as fractal dimension and approximate entropy in addition to the common time and frequency domain measures of both heart period and heart rate. This article evaluates the differences in using heart rate versus heart period to estimate fractal dimensions and approximate entropies of these time series.
2.Twenty-four-hour ECG was recorded in 23 normal subjects using Holter records. Time series of heart rate and heart period were analysed using fractal dimensions, approximate entropies and spectral analysis for the quantification of absolute and relative heart period variability in bands of ultra low (< 0.0033 ;Hz), very low (0.0033–0.04 ;Hz), low (0.04–0.15 ;Hz) and high (0.15–0.5 ;Hz) frequency.
3.Linear detrending of the time series did not significantly change the fractal dimension or approximate entropy values. We found significant differences in the analyses using heart rate versus heart period between waking up and sleep conditions for fractal dimensions, approximate entropies and absolute spectral powers, especially for the power in the band of 0.0033–0.5 ;Hz. Log transformation of the data revealed identical fractal dimension values for both heart rate and heart period. Mean heart period correlated significantly better with fractal dimensions and approximate entropies of heart period than did corresponding heart rate measures.
4.Studies using heart period measures should take the effect of mean heart period into account even for the analyses of fractal dimension and approximate entropy. As the sleep–awake differences in fractal dimensions and approximate entropies are different between heart rate and heart period, the results should be interpreted accordingly.