Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients.

Recent studies showed that tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as high-sensitive C-reactive protein (hsCRP) levels are predictive factors of cardiovascular risk. However, the effect of cardiac rehabilitation (CR) intervention in coronary artery disease (CAD) patients on these factors is not known. The aim of this study was to evaluate the effects of CR and exercise on hsCRP and inflammatory cytokine levels in patients with CAD after percutaneous coronary intervention (PCI). CAD patients who underwent PCI were divided into a CR and exercise group (CRE, n = 29) or a control group (CON, n = 10). CR and exercise consisted of 6 weeks supervised exercise training and 8 weeks home-based, self-managed exercise. Compared to pre-experimental levels, TNF-alpha (by 20.4%; p = 0.006) and IL-6 (by 49.0%; p < 0.0001), as well as hsCRP (by 59.4%; p < 0.0001), were markedly decreased after CR and exercise in CAD patients but not in control group, except for IL-6 (by 41.6%; p = 0.001). However, there was no significant alteration of adiposity-related variables such as BMI, percent body fat, and waist circumferences, in both groups. We suggest that CR and exercise in CAD patients after PCI induce significant reduction in hsCRP and inflammatory cytokines (TNF-alpha and IL-6), and marked increase in exercise tolerance and capacity.

Effect of cardiac rehabilitation and statin treatment on anti-HSP antibody titers in patients with coronary artery disease after percutaneous coronary intervention.

Accumulating evidence suggests that higher antibody titers to heat shock proteins (HSPs) are associated with the development and severity of atherosclerosis. The aim of this study was to evaluate the impact of cardiac rehabilitation therapy (CRT) or stain treatment (STT) or a combination of both (COM) on anti-HSP antibodies in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Clinical evaluation of subjects was performed both at the commencement and completion of the 14 weeks of treatment. CRT consisted of a supervised 6 weeks of exercise following hospital discharge and 8 weeks of home stay exercise. Patients assigned to statin therapy were treated with 80 mg per day of fluvastatin. Blood samples from 39 patients were analyzed for antibodies to HSP60 and HSP70 by ELISA. Biochemical parameters, including lipids, high-sensitivity C reactive protein (hsCRP), and interleukin-6 (IL-6), were also analyzed. We found that CRT and COM reduced antibody titers to HSP60 and HSP70 in CAD patients (by 3.79 and 10.00% of anti-HSP60, and by 5.74 and 3.45% of anti-HSP70, respectively) but statin treatment reduced only antibody titers to HSP70 (by 3.83%). There was a significant correlation between antibody titers to HSP60 versus HSP70. Considering the fact that antibody titers to HSPs are associated with the autoimmune process in CAD, CRT and COM have greater effects on reduction in autoimmune reaction after PCI than statin treatment. This reduction was accompanied by greater improvements in blood biochemical variables, such as lipids, hsCRP, and IL-6 after CRT and COM.

Prolonged residence of temperate natives in the tropics produces a suppression of sweating.

Tropical natives possess heat tolerance due to the ability to off-load endogenous and exogenous heat efficiently using a minimum amount of sweat. On the other hand, exposure of temperate natives to heat results in exaggerated production of sweat, of which part is lost by dripping and, thus, not available for evaporation. How sweating is modified in natives of temperate climate zones by prolonged residence in the tropics is not well-understood. The aim of this study was to investigate possible changes in the peripheral sweating mechanisms. Sweating responses to iontophoretically applied acetylcholine (ACh) were compared between Japanese subjects having either permanently resided in Japan (Japan resident Japanese, JRJ) or having stayed in the tropics for 2 years or longer (Tropics resident Japanese, TRJ). Quantitative sudomotor axon reflex tests by iontophoresis of ACh (10%, 2 mA for 5 min) were applied to determine directly activated (DIR) and axon reflex-mediated sweating during [AXR(1)] and after [AXR(2)] ACh iontophoresis. The sweat onset time of AXR(1) was 0.6 min shorter in JRJ than in TRJ (P<0.0001), and AXR(1) (P<0.0004), AXR(2) (P<0.0001), and DIR (P<0.0001) sweating responses were larger in JRJ than in TRJ. AXR and DIR sweating volumes (P<0.0001) were negatively correlated, and sweat onset times (P<0.0001) were positively correlated with the duration of residence in the tropics (2 to 13 years). The observed attenuation of sweating in TRJ suggests that temperate natives may acquire heat tolerance with improved sweating economy similar to tropical natives after prolonged residence in the tropics.

Cytoskeletal protein 4.1G is a binding partner of the metabotropic glutamate receptor subtype 1 alpha.

Recent evidence suggests that cytoskeletal proteins play important roles in the clustering and anchoring of glutamate receptors to the cell surface membrane. To examine further this issue, we tested for direct interactions between the metabotropic glutamate receptor subtype 1alpha (mGlu1alpha) and 4.1G, which is a member of the erythrocyte membrane, cytoskeletal protein 4.1 family. First, co-localization of 4.1G and mGlu1alpha was observed in cultured hippocampal neurons. Second, in transiently transfected HEK 293 cells and in whole rat brain tissue, direct interactions between mGlu1alpha and 4.1G were observed. Third, we were able to identify the C-terminal tail of mGlu1alpha as an essential region for mGlu1alpha-4.1G interactions. Fourth, 4.1 G influences mGlu1alpha-mediated cAMP accumulation. Finally, we found that 4.1G increases the ligand-binding ability of mGlu1alpha and alters its cellular distribution. These observations identify 4.1G as a novel binding partner of mGlu1alpha that can regulate the action of mGlu1alpha.

Relationships between IgG, IgM, IgE and resistance to reinfection during the early phase of infection with Clonorchis sinensis in rats.

An enzyme linked immunosorbent assay (ELISA) was used to study the correlation between the levels of IgG, IgM and IgE immunoglobulin isotypes and resistance to reinfection in rats during the first month of infection with Clonorchis sinensis. Rats were infected with Clonorchis sinensis (primary infection), and then treated with praziquantel on the 1st, 3rd, 7th, 14th and 28th day post infection (p.i.). To measure resistance, rats were re-infected with C. sinensis (secondary infection), 2 weeks after the treatment and worms were recovered 4 weeks later. During the primary infection, significantly increased levels of IgG isotype were observed on days 14 and 28 p.i. (P < 0.001) and IgM levels were significantly increased on 3rd and 28th day (P < 0.001). During the secondary infection, significantly increased levels of IgG isotype were found from 3rd to 28th day and IgE isotype on 7th and 14th day (P < 0.01) while significant levels of IgM were found on the 3rd and 28th day (P < 0.05). Furthermore, significant differences of worm numbers between infected and control group was found on the 14th and 28th day (P < 0.001). An inverse correlation betwee the IgG levels and the resistance to re-infection was also observed (r = -0.948, P = 0.004), indicating that the resistance to reinfection is highly associated with the levels of IgG during the early phase of infection, and then with the IgM and IgE.

Cytoskeletal protein 4.1G binds to the third intracellular loop of the A1 adenosine receptor and inhibits receptor action.

To identify binding partners of the A1AR (A1 adenosine receptor), yeast two-hybrid screening of a rat embryonic cDNA library was performed. This procedure led to the identification of erythrocyte membrane cytoskeletal protein (represented as 4.1G) as an A1AR-binding partner. Truncation studies revealed that the C-terminal domain of 4.1G was essential for binding to A1ARs and that the C-terminal domain of 4.1G and the third intracellular loop of A1ARs interacted. A1AR-4.1G interaction was also confirmed in studies using brain tissue. Studies in HEK-293 (human embryonic kidney 293) cells and Chinese-hamster ovary cells showed that 4.1G interfered with A1AR signal transduction, as 4.1G reduced A1AR-mediated inhibition of cAMP accumulation and intracellular calcium release. 4.1G also altered cell-surface A1AR expression. These observations identify 4.1G as a novel A1AR-binding partner that can regulate adenosine action.

Oligodendrocytes express functional A1 adenosine receptors that stimulate cellular migration.

A1 adenosine receptors (A1ARs) exert important effects in the central nervous system. However, the expression and function of A1ARs in oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLGs) is unclear. To address this issue, we examined A1AR expression during different stages of oligodendrocyte development. Radioreceptor studies showed that membranes prepared from OPCs and OLGs expressed high-affinity A1ARs with Kd values of 1.35 +/- 0.33 and 1.2 +/- 0.27 nM for [3H]CCPA, 1.17 +/- 0.24 and 1.4 +/- 0.34 nM for [3H]DPCPX, respectively. Bmax values were 64.31 +/- 6.14 and 75 +/- 6 fmol/mg protein for [3H]CCPA, and 153 +/- 12 and 205 +/- 17.8 fmol/mg protein for [3H]DPCPX, respectively. Activation of A1ARs using N6-cyclopentyladenosine (CPA) reduced both forskolin- and N-ethylcarboxyamidoadenosine (NECA)-stimulated cAMP accumulation, but did not affect basal cAMP levels. Activation of A1ARs by CPA stimulated OPC migration, but did not affect cell viability, proliferation, or differentiation. These results show that OPCs and OLGs express functional A1ARs that can stimulate the migration of OPCs.

A1 adenosine receptor activation induces ventriculomegaly and white matter loss.

A1 adenosine receptors (A1ARs) are widely expressed in the brain during development. To examine whether A1AR activation can alter postnatal brain formation, neonatal rats from postnatal days 3 to 14 were treated with the A1AR agonist N6-cyclopentyladenosine (CPA) in the presence or absence of the peripheral A1AR antagonist 8-(p-sulfophenyl)-theophylline (8SPT). CPA or CPA + 8SPT treatment resulted in reductions in white matter volume, ventriculomegaly, and neuronal loss. Quantitative electron microscopy revealed reductions in total axon volume following A1AR agonist treatment. We also observed reduced expression of myelin basic protein in treated animals. Showing that functional A1ARs were present over the ranges of ages studies, high levels of specific [3H]CCPA binding were observed at PD 4, 7 and 14, and receptor-G protein coupling was present at each age. These observations show that activation of A1ARs with doses of CPA that mimic the effects of high adenosine levels results in damage to the developing brain.

Ethanol alters glutamate but not adenosine uptake in rat astrocytes: evidence for protein kinase C involvement.

Glutamate is the primary excitatory neurotransmitter in brain. By stimulating neuronal activity, glutamate increases cellular energy utilization, enhances ATP hydrolysis and promotes the formation of adenosine. Adenosine has receptor-mediated effects that reduce or oppose the excitatory effects of glutamate. As a possible mechanism for ethanol's ability to inhibit excitatory effects of glutamate and enhance inhibitory effects of adenosine, we tested the hypothesis that ethanol promotes [3H]glutamate uptake and inhibits [3H]adenosine uptake. Using primary cultures of rat astrocytes, we found that acute treatment with ethanol (50 mM, 30 min) inhibited [3H]glutamate uptake and reduced protein kinase C (PKC)-induced stimulation of [3H]glutamate uptake. Prolonged treatment (50 mM, 3 day) with ethanol, however, increased both [3H]glutamate uptake and PKC activity. Contrary to other cell types, neither acute or chronic ethanol exposure affected [3H]adenosine uptake in astrocytes. These data indicate that in rat cortical astrocytes ethanol affects [3H]glutamate uptake but not [3H]adenosine uptake by affecting PKC modulation of transporter activity.

A preliminary investigation of the effects of maternal ethanol intake during gestation and lactation on brain adenosine A(1) receptor expression in rat offspring.

Ethanol exposure during fetal development can result in behavioral and neurological deficits, including reduced cognitive functions, retarded growth, and craniofacial abnormalities. Adenosine is an endogenous neuromodulator that fine-tunes the release and/or synaptic activities of several neurotransmitters, including glutamate, dopamine, and serotonin. Our aim was to determine whether ethanol exposure during early development affects adenosine receptors, particularly the A1 receptor subtype, in adult rats. Female rats were given water or 15% (vol/vol) ethanol in water prior to mating and throughout gestation and lactation. Sixty-day-old male rat offspring from these dams were randomly selected and assayed for adenosine A1 receptor expression in four brain areas: cortex, cerebellum, hippocampus, and striatum. Our results indicate that ethanol intake by dams decreased body and brain weights of offspring and reduced both A1 receptor mRNA and protein density in cortex and cerebellum. These preliminary findings indicate that ethanol intake by dams during pregnancy and lactation can affect adenosine A1 receptor signalling in the offspring. A pair-fed controlled study is warranted to explore these findings further.