The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 µmol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

Effects of chronic corticosterone and imipramine administration on panic and anxiety-related responses

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.

Heat-treatment reduces anti-nutritional phytochemicals and maintains protein quality in genetically improved hulled soybean flour

The soybean is a protein source of high biological value. However, the presence of anti-nutritional factors affects its protein quality and limits the bioavailability of other nutrients. The effect of heat-treatment, 150 ºC for 30 minutes, on hulled and hull-less soybean flour from the cultivar UFVTN 105AP on urease, trypsin inhibitor activity, protein solubility, amino acid profile, and in vivo protein quality was investigated. The treatment reduced the trypsin inhibitor activity and urease, but it did not affect protein solubility. Protein Efficiency Coefficient (PER) values of the flours were similar, and the PER of the hull-less soybean flour did not differ from casein. The Net Protein Ratio (NPR) did not differ between the experimental groups. The True Digestibility (TD) of the flours did not differ, but both were lower in casein and the Protein Digestibility Corrected Amino Acid Score (PDCCAS) was lower than the TD, due to limited valine determined by the chemical score. Therefore, the flours showed reduced anti-nutritional phytochemicals and similar protein quality, and therefore the whole flours can be used as a source of high quality protein.

Immediate and enduring effects of corticosterone administration during adolescence and adulthood on anxiety and depressive behavior in male rats

Previous research has shown that the stress hormone corticosterone can increase depressive and anxiety-like behavior in rats as well as dampen the HPA response to a novel stressor (Kalynchuk et aI., 2004; Johnson et aI., 2006). Several studies have also shown that adolescence is a period of increased sensitivity to the negative effects of stressors (reviewed in McCormick et aI., 2010), which are often the result of exposure to corticosterone, and yet there is no research to date examining the effects of corticosterone administration during adolescence. The purpose of these experiments is to determine both the immediate and enduring effects of prolonged exposure to corticosterone in adolescence and adulthood on anxiety-like behavior, depressive behavior, and the HPA response. In Experiment 1 adolescent and adult rats were administered an injection of 40 mg/kg of corticosterone or vehicle daily for 16 days. Ha l f of the rats were then tested on the elevated plus maze (EPM) one day after their last injection, and the following day were tested on the forced swim test (FST). After the FST, which is a stressor, blood samples were collected at three time points, and the plasma concentrations of corticosterone were determined using a radioimmunoassay. The remaining rats were left undisturbed for three weeks, and then underwent the same testing as the first group. Corticosterone treatment had little effect on anxiety-like and depressive behavior, but it did alter the HPA response to the FST. In those rats tested soon after the period of injections, corticosterone dampened the HPA response as compared to vehicle treated rats in both adolescent and adult treated rats. For the adolescent treated rats that were tested several weeks later, corticosterone treatment increased HPA response as compared to the vehicle treated rats, but the same was not true for the adult treated rats. I t was hypothesized that the lack of behavioral effects of the corticosterone treatment may be the result of the vehicle injections inducing a stress response and thereby both groups would have similarly altered behavior. In Experiment 2 rats were administered corticosterone dissolved in their drinking water with 2.5% ethanol, or jus t the 2.5% ethanol or plain water, to determine the effects of corticosterone treatment without a stressor present. The regular drinking water was replaced with treated water for 16 days either during adulthood or adolescence, and as before, rats were either tested in the FST one day after the water was removed or three weeks later. Again there was no effect of treatment on depressive behavior. Similar to what was observed in Experiment 1, corticosterone treatment dampened the HPA response to a stressor for the rats tested soon after the treatment period. However, in Experiment 2 there was no effect of treatment on HPA response in those rats tested several weeks after they were treated. These results indicate that corticosterone can have a lasting effect on the HPA when administered in adolescence by injections but not in drinking water, which is likely because of the different schedules of exposure and rates of absorption between the two administration methods.

Comparison of heat-treated rapeseed expeller and solvent-extracted soya-bean meal as protein supplements for dairy cows given grass silage-based diets

Sixteen early to mid lactation Finnish Ayrshire dairy cows were used in a cyclic change-over experiment with four 21-day experimental periods and a 4 5 2 factorial arrangement of treatments to evaluate the effects of heat-treated rapeseed expeller and solvent-extracted soya-bean meal protein supplements on animal performance. Dietary treatments consisted of grass silage offered ad libitum supplemented with a fixed amount of a cereal based concentrate (10 kg/day on a fresh weight basis) containing 120, 150, 180 or 210 g crude protein (CP) per kg dry matter (DM). Concentrate CP content was manipulated by replacement of basal ingredients (g/kg) with either rapeseed expeller (R; 120, 240 and 360) or soya-bean meal (S; 80, 160 and 240). Increases in concentrate CP stimulated linear increases (P < 0.05) in silage intake (mean 22.5 and 23.8 g DM per g/kg increase in dietary CP content, for R and S, respectively) and milk production. Concentrate inclusion of rapeseed expeller elicited higher (P < 0.01) milk yield and milk protein output responses (mean 108 and 3.71 g/day per g/kg DM increase in dietary CP content) than soya-bean meal (corresponding values 62 and 2.57). Improvements in the apparent utilization of dietary nitrogen for milk protein synthesis (mean 0.282 and 0.274, for R and S, respectively) were associated with higher (P < 0.05) plasma concentrations of histidine, branched-chain, essential and total amino acids (35, 482, 902 and 2240 and 26, 410, 800 and 2119 mu mol/l, respectively) and lower (P < 0.01) concentrations of urea (corresponding values 4.11 and 4.52 mmol/l). Heat-treated rapeseed expeller proved to be a more effective protein supplement than solvent-extracted soya-bean meal for cows offered grass silage-based diets.

A physical organic chemistry approach to dissolution of cellulose: effects of cellulose mercerization on its properties and on the kinetics of its decrystallization

The effects of alkali treatment on the structural characteristics of cotton linters and sisal cellulose samples have been studied. Mercerization results in a decrease in the indices of crystallinity and the degrees of polymerization, and an increase in the alpha-cellulose contents of the samples. The relevance of the structural properties of cellulose to its dissolution is probed by studying the kinetics of cellulose decrystallization, prior to its solubilization in LiCl/N,N-dimethylacetamide (DMAc). Our data show that the decrystallization rate constants and activation parameters are only slightly dependent on the physico-chemical properties of the starting celluloses. This multi-step reaction is accompanied by a small enthalpy and large, negative, entropy of activation. These results are analyzed in terms of the interactions within the biopolymer chains during decrystallization, as well as those between the two ions of the electrolyte and both DMAc and cellulose.

A metallurgical study of aluminium alloys used as aircraft components

The effects of heat treatment on morphologies and microstructures of Al 2024 and Al 7050 alloys, used as aircraft components, were studied by metallographic techniques. Light microscopy (LM) and quantitative image analysis were used to characterize the precipitate dispersion and morphology for these alloys. The application of the scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) combined techniques for studying these multiphase systems makes it possible to distinguish and quantify the different phases in the surface structure. Xray diffraction also permitted a qualitative comparison of the structures before and after heat treatments.

Analyses of fatigue data in 4340 high strength steel after cadmium electroplating

Bending fatigue tests were carried out to clarify the effects of heat treatment parameters: temperature and time after cadmium electroplating on a high strength steel, to avoid hydrogen embrittlement. Temperatures heat of 190 degrees C, 230 degrees C, 250 degrees C and 300 degrees C at 3, 8 and 24 hours together with the base material electroplated, with and without heat treatment, resulted in 14 conditions studied with respect to fatigue behaviour. Statistical data analysis was performed to identify the best combination temperature/time regarding fatigue strength of the ABNT 4340 steel and the results obtained revealed that the fatigue strength depend on temperature/time conditions.

Effect of chronic treatment with Clomipramine on food intake, macronutrient selection and body weight gain in rats

Long-term treatment with clomipramine (CMI), a tricyclic antidepressant, induces food craving and body weight gain in patients. The present study investigated the effects of chronic treatment with CMI on total food intake, macronutrient selection, and body weight gain in rats. Male Wistar rats were maintained on a dietary self-selection regime with separate sources of protein, fat and carbohydrate. Animals received i.p. injections of CMI (0, 3, 10, 30 mg/kg) during 27 consecutive days. Food consumption and body weight were recorded daily and results were calculated as average of three consecutive days, namely during pre-treatment (3 d before pharmacological treatment), treatment (7th-9th; l6th-l8th and 25th-27th days), and post-treatment (28th-33rd days). Results showed that CMI (30 mg/kg) significantly decreased energy intake during all treatment period, an effect that was related to a decrease in both carbohydrate-rich diet intake and body weight gain. At dose of 3 mg/kg CMI increased the total energy intake in the 16th-18th days, suggesting an apparent biphasic effect of chronic treatment with CMI on caloric intake. Chronic administration with CMI (27 d) did not alter protein-rich or fat-rich diet consumption. The main result of this study indicated that chronic treatment with CMI decreases rather than increase food consumption and body weight gain in rats exposed to a macronutrient self-selection procedure.

The effect of timing of thermal conditioning during incubation on embryo physiological parameters and its relationship to thermotolerance in adult broiler chickens

Previously, we reported that thermal conditioning at 39degreesC on days 13-17 of incubation of broiler eggs enabled thermotolerance during post-hatch growth (J. Therm. Biol. 28 (2003) 133). Tolerance to a temperature of 30degreesC was accompanied by changes in thyroid hormones and metabolic parameters. In the current study, we determined the mechanism of epigenetic heat adaptation during embryonic age by measuring blood physiological parameters that may be associated with the ultimate effects of thermal conditioning. Hatching eggs from Ross breeders were subjected to heat treatment of 39degreesC at days 13, 14, 15, 16 and 17 of incubation for 2 h per day. Control eggs were incubated at 37.6degreesC. Samples of eggs were withdrawn on each day of thermal conditioning and at internal pipping (IP) to obtain blood samples from embryos. The remaining eggs were weighed at day 18 and transferred to hatchers. The timing of IP, external pipping (EP) and hatching were monitored every 2 h. At hatch, chicks were weighed and hatchability was determined. Blood samples were obtained from samples of day-old chicks. T3, T4, corticosterone, pCO(2), pO(2) levels were determined in the blood. Blood pH was measured and T3/T4 ratios were calculated. Heat conditioning significantly increased corticosterone and pO(2) levels and blood pH but depressed pCO(2) at day 14. These were followed by a significant depression of T4 level on day 15. Remarkably, at day 16, all these parameters were back to normal as in the control embryos. Hatching was delayed by thermal conditioning probably as a result of the depressed corticosterone levels at IP. Hatchability was also lower in the heat-treated group but 1-day old chick weights were comparable to those of the controls. The result suggests that epigenetic thermal conditioning involves changes in these physiological parameters and probably serve as a method for epigenetic temperature adaptation since the same mechanisms are employed for coping with heat during post-embryonic growth. It also suggests that days 14-15 may be the optimal and most sensitive timing for evoking this mechanism during embryonic development. The adverse effects of heat treatment observed in this study may have been due to the continued exposure to heat until day 17. Fine-tuning thermal conditioning to days 14-15 only may improve these production parameters. (C) 2003 Elsevier Ltd. All rights reserved.

DIRECT EFFECTS OF METFORMIN ON PI3K AND RAS SIGNALING IN ENDOMETRIAL CANCER

Metformin has antiproliferative effects through the activation of AMPK and has gained interest as an antineoplastic agent in several cancer types, although studies in endometrial cancer (EC) are limited. The aims of this project were to evaluate pathways targeted by metformin in EC, investigate mechanisms by which metformin exerts its antiproliferative effects, and explore rational combination therapies with other targeted agents. Three EC cell lines were used to evaluate metformin’s effect on cell proliferation, PI3K and Ras-MAPK signaling, and apoptosis. A xenograft mouse model was also used to evaluate the effects of metformin treatment on in vivo tumor growth. These preliminary studies demonstrated that K-Ras mutant cell lines exhibited a decreased proliferative rate, reduced tumor growth, and increased apoptosis in response to metformin compared to K-Ras wild-type cells. To test the hypothesis that mutant K-Ras may predict response to metformin, murine EC cells with loss of PTEN and expressing mutant K-RasG12D were transfected to re-express PTEN or have K-Ras silenced using siRNA. While PTEN expression did not alter response to metformin, cells in which K-Ras was silenced displayed reduced sensitivity to metformin. Mislocalization of K-Ras to the cytoplasm is associated with decreased signaling and induction of apoptosis. Metformin’s effect on K-Ras localization was analyzed by confocal microscopy in cells expressing oncogenic GFP-K-RasG12V. Metformin demonstrated concentration-dependent mislocalization of K-Ras to the cytoplasm. Mislocalization of K-Ras to the cytoplasm was confirmed in K-Ras mutant EC cells (Hec1A) by cell fractionation in response to metformin 1 and 5 mM (p=0.008 and p=0.004). This effect appears to be AMPK-independent as combined treatment with Compound C, an AMPK inhibitor, did not alter K-Ras localization. Furthermore, treatment of EC cells with metformin in combination with PI3K inhibitors resulted in a significant decrease in proliferation than either agent or metformin alone. While metformin exerts antineoplastic effects by activation of AMPK and decreased PI3K signaling, our data suggest that metformin may also disrupt localization of K-Ras and hence its signaling in an AMPK-independent manner. This has important implications in defining patients who may benefit from metformin in combination with other targeted agents, such as mTOR inhibitors.

Characterization of heat-treated porous carbons using argon adsorption

The microstructural variation of Norit RI Extra activated carbon, progressively heated at 1373 K, was explored in terms of pore size and pore wall thickness distributions, for various periods of heating time, determined by argon adsorption at 87 K, both using an infinite as well as and finite wall thickness model. The latter approach has recently been developed in our laboratory and has been applied to several virgin carbons. The current results show significant variations in small pore size regions (< 7 angstrom) in association with strong growth of thick walls having at least three carbon sheets, as a result of heat treatment. In particular, shrinkage of the smallest pores due to strong interaction between their opposite walls as well as smoothening of carbon wall surfaces due to an increase in graphitization degree under thermal treatment have been found. Further, the results of pore wall thickness distribution are well corroborated by X-ray diffraction. The results of pore size and pore wall thickness distributions are also shown to be consistent with transmission electron microscopy analyses. (c) 2005 Elsevier Ltd. All rights reserved.

The roles of exercise-induced immune system disturbances in the pathology of heat stroke - The dual pathway model of heat stroke

Heat stroke is a life-threatening condition that can be fatal if not appropriately managed. Although heat stroke has been recognised as a medical condition for centuries, a universally accepted definition of heat stroke is lacking and the pathology of heat stroke is not fully understood. Information derived from autopsy reports and the clinical presentation of patients with heat stroke indicates that hyperthermia, septicaemia, central nervous system impairment and cardiovascular failure play important roles in the pathology of heat stroke. The current models of heat stroke advocate that heat stroke is triggered by hyperthermia but is driven by endotoxaemia. Endotoxaemia triggers the systemic inflammatory response, which can lead to systemic coagulation and haemorrhage, necrosis, cell death and multi-organ failure. However, the current heat stroke models cannot fully explain the discrepancies in high core temperature (Tc) as a trigger of heat stroke within and between individuals. Research on the concept of critical Tc: as a limitation to endurance exercise implies that a high Tc may function as a signal to trigger the protective mechanisms against heat stroke. Athletes undergoing a period of intense training are subjected to a variety of immune and gastrointestinal (GI) disturbances. The immune disturbances include the suppression of immune cells and their functions, suppression of cell-mediated immunity, translocation of lipopolysaccharide (LPS), suppression of anti-LPS antibodies, increased macrophage activity due to muscle tissue damage, and increased concentration of circulating inflammatory and pyrogenic cytokines. Common symptoms of exercise-induced GI disturbances include diarrhoea, vomiting, gastrointestinal bleeding, and cramps, which may increase gut-related LPS translocation. This article discusses the current evidence that supports the argument that these exercise-induced immune and GI disturbances may contribute to the development of endotoxaemia and heat stroke. When endotoxaemia can be tolerated or prevented, continuing exercise and heat exposure will elevate Tc to a higher level (> 42 degrees C), where heat stroke may occur through the direct thermal effects of heat on organ tissues and cells. We also discuss the evidence suggesting that heat stroke may occur through endotoxaemia (heat sepsis), the primary pathway of heat stroke, or hyperthermia, the secondary pathway of heat stroke. The existence of these two pathways of heat stroke and the contribution of exercise-induced immune and GI disturbances in the primary pathway of heat stroke are illustrated in the dual pathway model of heat stroke. This model of heat stroke suggests that prolonged intense exercise suppresses anti-LPS mechanisms, and promotes inflammatory and pyrogenic activities in the pathway of heat stroke.

Seasonal changes of heat and moisture fluxes from the Caspian Sea surface and its effect on synoptic systems with heavy rainfalls in southern shores of the sea during 2005-2010

Caspian Sea with its unique characteristics is a significant source to supply required heat and moisture for passing weather systems over the north of Iran. Investigation of heat and moisture fluxes in the region and their effects on these systems that could lead to floods and major financial and human losses is essential in weather forecasting. Nowadays by improvement of numerical weather and climate prediction models and the increasing need to more accurate forecasting of heavy rainfall, the evaluation and verification of these models has been become much more important. In this study we have used the WRF model as a research-practical one with many valuable characteristics and flexibilities. In this research, the effects of heat and moisture fluxes of Caspian Sea on the synoptic and dynamical structure of 20 selective systems associated with heavy rainfall in the southern shores of Caspian Sea are investigated. These systems are selected based on the rainfall data gathered by three local stations named: Rasht, Babolsar and Gorgan in different seasons during a five-year period (2005-2010) with maximum amount of rainfall through the 24 hours of a day. In addition to synoptic analyses of these systems, the WRF model with and without surface flues was run using the two nested grids with the horizontal resolutions of 12 and 36 km. The results show that there are good consistencies between the predicted distribution of rainfall field, time of beginning and end of rainfall by the model and the observations. But the model underestimates the amounts of rainfall and the maximum difference with the observation is about 69%. Also, no significant changes in the results are seen when the domain and the resolution of computations are changed. The other noticeable point is that the systems are severely weakened by removing heat and moisture fluxes and thereby the amounts of large scale rainfall are decreased up to 77% and the convective rainfalls tend to zero.

Wood as a model material for medical biomaterials. In vivo and in vitro studies with bone and Betula pubescens Ehrh

Novel biomaterials are needed to fill the demand of tailored bone substitutes required by an ever‐expanding array of surgical procedures and techniques. Wood, a natural fiber composite, modified with heat treatment to alter its composition, may provide a novel approach to the further development of hierarchically structured biomaterials. The suitability of wood as a model biomaterial as well as the effects of heat treatment on the osteoconductivity of wood was studied by placing untreated and heat‐treated (at 220 C , 200 degrees and 140 degrees for 2 h) birch implants (size 4 x 7mm) into drill cavities in the distal femur of rabbits. The follow‐up period was 4, 8 and 20 weeks in all in vivo experiments. The flexural properties of wood as well as dimensional changes and hydroxyl apatite formation on the surface of wood (untreated, 140 degrees C and 200 degrees C heat‐treated wood) were tested using 3‐point bending and compression tests and immersion in simulated body fluid. The effect of premeasurement grinding and the effect of heat treatment on the surface roughness and contour of wood were tested with contact stylus and non‐contact profilometry. The effects of heat treatment of wood on its interactions with biological fluids was assessed using two different test media and real human blood in liquid penetration tests. The results of the in vivo experiments showed implanted wood to be well tolerated, with no implants rejected due to foreign body reactions. Heat treatment had significant effects on the biocompatibility of wood, allowing host bone to grow into tight contact with the implant, with occasional bone ingrowth into the channels of the wood implant. The results of the liquid immersion experiments showed hydroxyl apatite formation only in the most extensively heat‐treated wood specimens, which supported the results of the in vivo experiments. Parallel conclusions could be drawn based on the results of the liquid penetration test where human blood had the most favorable interaction with the most extensively heat‐treated wood of the compared materials (untreated, 140 degrees C and 200 degrees C heat‐treated wood). The increasing biocompatibility was inferred to result mainly from changes in the chemical composition of wood induced by the heat treatment, namely the altered arrangement and concentrations of functional chemical groups. However, the influence of microscopic changes in the cell walls, surface roughness and contour cannot be totally excluded. The heat treatment was hypothesized to produce a functional change in the liquid distribution within wood, which could have biological relevance. It was concluded that the highly evolved hierarchical anatomy of wood could yield information for the future development of bulk bone substitutes according to the ideology of bioinspiration. Furthermore, the results of the biomechanical tests established that heat treatment alters various biologically relevant mechanical properties of wood, thus expanding the possibilities of wood as a model material, which could include e.g. scaffold applications, bulk bone applications and serving as a tool for both mechanical testing and for further development of synthetic fiber reinforced composites.