Abstract. It was previously demonstrated that preischemic A 1 adenosine receptor (AR) activation protects renal function after ischemia-reperfusion (IR) injury in rats. The role of the A 1 AR in modulating inflammation, necrosis, and apoptosis in the kidney after IR renal injury was further characterized. C57BL/6 mice were subjected to 30 min of renal ischemia, with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine or 2-chlorocyclopentyladenosine (selective A 1 AR antagonist and agonist, respectively). Plasma creatinine levels and renal inflammation, necrosis, and apoptosis were compared 24 h after renal injury. C57BL/6 mice that had been pretreated with the A 1 AR agonist demonstrated significantly improved renal function and reduced expression of inflammatory markers, necrosis, and apoptosis 24 h after IR injury. In contrast, C57BL/6 mice that had been pretreated with the A 1 AR antagonist demonstrated significantly worsened renal function and increased expression of inflammatory markers, necrosis, and apoptosis. In conclusion, it was demonstrated that endogenous and exogenous preischemic activation of the A 1 AR protects against IR injury in vivo, through mechanisms that reduce inflammation, necrosis, and apoptosis.Acute renal failure (ARF) secondary to ischemia-reperfusion (IR) injury continues to be a significant perioperative problem. ARF is frequently complicated by many other life-threatening complications, including sepsis and multiorgan failure. The prognosis for ARF is poor (with mortality rates of approximately 50%) and has changed little in the past 40 yr (1-3).We previously demonstrated that pharmacologic adenosine receptor (AR) modulation significantly affects renal function after IR injury in rats (4 -6). In particular, we demonstrated that preischemic activation of the A 1 AR attenuated renal failure after IR injury in vivo (4). We also demonstrated the cytoprotective effects of A 1 AR activation in cultured proximal tubule cells injured by H 2 O 2 or severe ATP depletion (7,8).Modulation of AR has been demonstrated to attenuate necrosis (9), inflammation (10,11), and apoptosis (12,13) after injury. Both apoptosis and necrosis contribute significantly to the pathogenesis of ARF after IR injury (14,15). Moreover, inflammatory renal injury is a significant component of necrotic renal cell death (16,17). It remains to be determined whether the renoprotective effect of preischemic A 1 AR activation is associated with modulation of apoptosis, necrosis, and/or inflammation. Therefore, in this study, we aimed to extend our previous findings regarding the mechanisms of A 1 AR effects on renal function after IR injury. We questioned whether the protective effects of A 1 AR activation were mediated through a decrease in the inflammatory response in the kidney and whether necrotic or apoptotic cell death was attenuated. We hypothesized that preischemic activation or inhibition of A 1 AR would decrease or increase levels of inflammation markers, respectively. Moreover, we hypothesized that nec...
The role of A3 adenosine receptors (ARs) in sepsis and inflammation is controversial. In this study, we determined the effects of A3AR modulation on mortality and hepatic and renal dysfunction in a murine model of sepsis. To induce sepsis, congenic A3AR knockout mice (A3AR KO) and wild-type control (A3AR WT) mice were subjected to cecal ligation and double puncture (CLP). A3AR KO mice had significantly worse 7-day survival compared with A3AR WT mice. A3AR KO mice also demonstrated significantly higher elevations in plasma creatinine, alanine aminotransferase, aspartate aminotransferase, keratinocyte-derived chemokine, and TNF-alpha 24 h after induction of sepsis compared with A3AR WT mice. Renal cortices from septic A3AR KO mice exhibited increased mRNA encoding proinflammatory cytokines and enhanced nuclear translocation of NF-kB compared with samples from A3AR WT mice. A3AR WT mice treated with N6-(3-iodobenzyl)ADO-5'N-methyluronamide (IB-MECA; a selective A3AR agonist) or 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191; a selective A3AR antagonist) had improved or worsened 7-day survival after induction of sepsis, respectively. Moreover, A3AR WT mice treated with IB-MECA or MRS-1191 showed acutely improved or worsened, respectively, renal and hepatic function following CLP. IB-MECA significantly reduced mortality in mice lacking the A1AR or A2aAR but not the A3AR, demonstrating specificity of IB-MECA in activating A3ARs and mediating protection against sepsis-induced mortality. We conclude that endogenous or exogenous A3AR activation confers significant protection from murine septic peritonitis primarily by attenuating the hyperacute inflammatory response in sepsis.
Our findings suggest a new paradigm for cervical tissue morphology-one that includes the possibility of a specialized sphincter at the internal os. This new paradigm introduces novel avenues to further investigate potential mechanisms of normal and premature cervical remodeling.
Adequate nutrition is critically important for the achievement of the adolescent athlete's optimal performance. The purpose of the present study was to evaluate the adequacy of macro-and micro-nutrients in the adolescent Greek female volleyball players' diet. The subjects of the study consisted of 16 players who were members of the Junior National Team (NP) and 49 players who participated in the Junior National Championship (CP). Dietary intake was assessed using a 3-day food record. Protein intake (16.0 ± 4.9% of total energy intake) was satisfactory, whereas fat consumption (37.5 ± 11.1%) was above recommended values and at the expense of carbohydrate intake (45.9 ± 12.5%). There were no significant differences between NP and CP concerning the intake of macronutrients, except for the fat intake (when this is expressed in grams per day and grams per kilogram of body weight and the saturated fat intake, which were both higher in NP compared to CP players (p < .05). The mean energy intake was 2013 ± 971 and 1529 ± 675 kcal for NP and CP, respectively (p < .05). NP, in particular, consumed fat and especially saturated fat in order to meet their energy needs. As for micronutrients, the volleyball players fell short of meeting the RDA values for calcium, iron, folic acid, magnesium, zinc, and vitamins A, B 1 , B 2 , and B 6 . There was no difference between NP and CP in micronutrient intake. In conclusion, subjects in the current study lacked proper nutrition in terms of quantity and quality.Key Words: nutrition, elite athletes, energy, team sports Adolescent athletes have increased energy needs because of physical activity and physical development. This is especially true for elite adolescent athletes, who exercise strenuously in order to maximize their performance. These athletes should consume high density food for both nutrients and kilocalories (32). Proper nutrition is essential for optimizing athletic performance (9). A general recommendation for all athletes is to consume 60-70% of total energy intake from carbohydrates (CHO), 12-15% from proteins, and 25-30% from fats (20).Generally, young athletes may be inclined to stress fracture (7). Proper nutrition can play a valuable role in avoiding such injuries, as inappropriate nutrition may
The prevalence of asthma has taken on pandemic proportions. Since this disease predisposes patients to severe acute airway constriction, novel mechanisms capable of promoting airway smooth muscle relaxation would be clinically valuable. We have recently demonstrated that activation of endogenous airway smooth muscle GABAA receptors potentiates -adrenoceptor-mediated relaxation, and molecular analysis of airway smooth muscle reveals that the ␣-subunit component of these GABAA receptors is limited to the ␣4-and ␣5-subunits. We questioned whether ligands with selective affinity for these GABAA receptors could promote relaxation of airway smooth muscle. RT-PCR analysis of GABAA receptor subunits was performed on RNA isolated by laser capture microdissection from human and guinea pig airway smooth muscle. Membrane potential and chloride-mediated current were measured in response to GABAA subunit-selective agonists in cultured human airway smooth muscle cells. Functional relaxation of precontracted guinea pig tracheal rings was assessed in the absence and presence of the ␣4-subunit-selective GABAA receptor agonists: gaboxadol, taurine, and a novel 8-methoxy imidazobenzodiazepine (CM-D-45). Only messenger RNA encoding the ␣4-and ␣5-GABAA receptor subunits was identified in RNA isolated by laser capture dissection from guinea pig and human airway smooth muscle tissues. Activation of airway smooth muscle GABAA receptors with agonists selective for these subunits resulted in appropriate membrane potential changes and chloride currents and promoted relaxation of airway smooth muscle. In conclusion, selective subunit targeting of endogenous airway smooth muscle-specific GABAA receptors may represent a novel therapeutic option for patients in severe bronchospasm.
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