Glucose feeding and exercise in trained rats: mechanisms for glycogen sparing

This investigation studied the effect of an oral glucose feeding on glycogen sparing during exercise in non-glycogen-depleted and glycogen-depleted endurance-trained rats. The non-glycogen-depleted rats received via a stomach tube 2 ml of a 20% glucose solution labeled with [U-14C]glucose just prior to exercise (1 h at 25 m/min). Another group of rats ran for 40 min at higher intensity to deplete glycogen stores, after which they received the same glucose feeding and continued running for 1 h at 25 m/min. The initial 40-min run depleted glycogen in heart, skeletal muscle, and liver. In the non-glycogen-depleted rats the glucose feeding spared glycogen in the liver, primarily from the oxidation of blood-borne glucose in muscle. In the glycogen-depleted rats, muscle glycogen was repleted after the feeding, but sources other than the administered glucose also contributed to glycogen synthesis. The results suggest that glycogen depletion rather than the glucose feeding per se stimulates glycogen resynthesis in muscle during exercise in endurance-trained rats.     

Neurovascular responses to mental stress in the supine and upright postures.

The purpose of this study was to determine neurovascular responses to mental stress (MS) in the supine and upright postures. MS was elicited in 23 subjects (26 +/- 1 yr) by 5 min of mental arithmetic. In study 1 (n = 9), Doppler ultrasound was used to measure mean blood flow velocity in the renal (RBFV) and superior mesenteric arteries (SMBFV), and venous occlusion plethysmography was used to measure forearm blood flow (FBF). In study 2 (n = 14), leg blood flow (LBF; n = 9) was measured by Doppler ultrasound, and muscle sympathetic nerve activity (MSNA; n = 5) was measured by microneurography. At rest, upright posture increased heart rate and MSNA and decreased LBF, FBF, RBFV, and SMBFV and their respective conductances. MS elicited similar increases in mean arterial blood pressure ( approximately 12 mmHg) and heart rate ( approximately 17 beats/min), regardless of posture. MS in both postures elicited a decrease in RBFV, SMBFV, and their conductances and an increase in LBF, FBF, and their conductances. Changes in blood flow were blunted in the upright posture in all vascular beds examined, but the pattern of the vascular response was the same as the supine posture. MS did not change MSNA in either posture (change: approximately 1 +/- 3 and approximately 3 +/- 3 bursts/min, respectively). In conclusion, the augmented sympathetic activity of the upright posture does not alter heart rate, mean arterial blood pressure, or MSNA responses to MS. MS elicits divergent vascular responses in the visceral and peripheral vasculature. These results indicate that, although the upright posture attenuates vascular responses to MS, the pattern of neurovascular responses does not differ between postures.     

Strengthening individual and family resilience against leprosy-related discrimination: A pilot intervention study

BackgroundLeprosy and leprosy-related stigma can have a major impact on psychosocial wellbeing of persons affected and their family members. Resilience is a process that incorporates many of the core skills and abilities which may enable people to address stigma and discrimination. The current study aimed to develop and pilot an intervention to strengthen individual and family resilience against leprosy-related discrimination.MethodologyWe used a quasi-experimental, before-after study design with a mixed methods approach. The 10-week family-based intervention was designed to strengthen the resilience of individuals and families by enhancing their protective abilities and capacity to overcome adversity. The study was conducted in two sites, urban areas in Telangana state, and in rural areas in Odisha state, India. Persons affected and their family members were included using purposive sampling. Two questionnaires were used pre-and post-intervention: the Connor-Davidson Resilience Scale (CD-RISC, maximum score 100, with high scores reflecting greater resilience) and the WHOQOL-BREF (maximum score of 130, with higher scores reflecting higher quality of life). In addition, semi-structured interviews were conducted post-intervention. Data were collected at baseline, a few weeks after completion of the intervention, and in the Odisha cohort again at six months after completion. Paired t-tests measured differences pre- and post- intervention. Qualitative data were thematically analysed.FindingsEighty participants across 20 families were included in the study (23 persons affected and 57 family members). We found a significant increase in CD-RISC scores for persons affected and family members from Odisha state (baseline 46.5, first follow-up 77.0, second follow-up 70.0), this improvement was maintained at six-month follow-up. There was no increase in CD-RISC scores post-intervention among participants from Telangana state. WHOQOL-BREF scores were significantly higher at follow-up for persons affected in both states, and for family members in Odisha state. No families dropped out of the study. In the qualitative feedback, all participants described drawing benefit from the programme. Participants especially appreciated the social dimensions of the intervention.ConclusionThis pilot study showed that the 10-week family-based intervention to strengthen resilience among persons affected by leprosy and their family members was feasible, and has the potential to improve resilience and quality of life. A large-scale efficacy trial is necessary to determine the effectiveness and long-term sustainability of the intervention.     

Drying Increases Intracellular Partitioning of Amphiphilic Substances into the Lipid Phase : Impact on Membrane Permeability and Significance for Desiccation Tolerance

Previously we proposed that endogenous amphiphilic substances may partition from the aqueous cytoplasm into the lipid phase during dehydration of desiccation-tolerant organ(ism)s and vice versa during rehydration. Their perturbing presence in membranes could thus explain the transient leakage from imbibing organisms. To study the mechanism of this phenomenon, amphiphilic nitroxide spin probes were introduced into the pollen of a model organism, Typha latifolia, and their partitioning behavior during dehydration and rehydration was analyzed by electron paramagnetic resonance spectroscopy. In hydrated pollen the spin probes mainly occurred in the aqueous phase; during dehydration, however, the amphiphilic spin probes partitioned into the lipid phase and had disappeared from the aqueous phase below 0.4 g water g⁻¹ dry weight. During rehydration the probes reappeared in the aqueous phase above 0.4 g water g⁻¹ dry weight. The partitioning back into the cytoplasm coincided with the decrease of the initially high plasma membrane permeability. A charged polar spin probe was trapped in the cytoplasm during drying. Liposome experiments showed that partitioning of an amphiphilic spin probe into the bilayer during dehydration caused transient leakage during rehydration. This was also observed with endogenous amphipaths that were extracted from pollen, implying similar partitioning behavior. In view of the fluidizing effect on membranes and the antioxidant properties of many endogenous amphipaths, we suggest that partitioning with drying may be pivotal to desiccation tolerance, despite the risk of imbibitional leakage.     

A short course of infusion of a hydrogen sulfide-donor attenuates endotoxemia induced organ injury via stimulation of anti-inflammatory pathways,with no additional protection from prolonged infusion

Organ failure is associated with increased mortality and morbidity in patients with systemic inflammatory response syndrome. Previously, we showed that a short course of infusion of a hydrogen sulfide (H₂S) donor reduced metabolism with concurrent reduction of lung injury. Here, we hypothesize that prolonged H₂S infusion is more protective than a short course in endotoxemia with organ failure. Also, as H₂S has both pro- and anti-inflammatory effects, we explored the effect of H₂S on interleukin production.Endotoxemia was induced by an intravenous bolus injection of LPS (7.5 mg/kg) in mechanically ventilated rats. H₂S donor NaHS (2 mg/kg) or vehicle (saline) was infused and organ injury was determined after either 4 or 8 h. A short course of H₂S infusion was associated with reduction of lung and kidney injury. Prolonged infusion did not enhance protection. Systemically, infusion of H₂S increased both the pro-inflammatory response during endotoxemia, as demonstrated by increased TNF-α levels, as well as the anti-inflammatory response, as demonstrated by increased IL-10 levels. In LPS-stimulated whole blood of healthy volunteers, co-incubation with H₂S had solely anti-inflammatory effects, resulting in decreased TNF-α levels and increased IL-10 levels. Co-incubation with a neutralizing IL-10 antibody partly abrogated the decrease in TNF-α levels. In conclusion, a short course of H₂S infusion reduced organ injury during endotoxemia, at least in part via upregulation of IL-10.     

Dehydration-induced conformational changes of poly-l-lysine as influenced by drying rate and carbohydrates

The conformation of hydrated and air-dried poly-l-lysine in thin films was studied using Fourier transform IR spectroscopy in the amide-I region. Hydrated poly-l-lysine has a random coil conformation. Upon slow drying of small droplets of the polypeptide solution over a period of several hours, an extended β-sheet conformation is adopted. This conformational transition can be prevented by fast air-drying within 2–3 min. Slow air-drying in the presence of sucrose also preserves the aqueous conformation and results in the formation of a glassy state. Comparison of shifts of the OH band with temperature indicates that sucrose/poly-l-lysine mixtures form a molecularly more densely packed glassy matrix, having a higher glass transition temperature (T_g), than sucrose alone. Whether direct interaction of sugar and polypeptide or glass formation is involved in the stabilization during slow air-drying was studied by drying in the presence of glucose or dextran. Compared with dextran (and sucrose to a lesser extent), glucose gives superior protection. Dried glucose has the lowest T_g and the best interacting properties. We conclude that either immobilization by fast air-drying or sufficient interaction with a protectant through hydrogen bonding (slow drying) plays the leading role in the preservation of the aqueous protein structure.