Bedside echocardiography provided crucial information leading to the recognition of septic myocardial dysfunction and uncorrected hypovolemia that was not apparent on clinical assessment. With invasive blood pressure monitoring, echocardiography affords a simple noninvasive tool to determine the cause of low cardiac output and the physiological basis for adjustment of therapy in patients who remain in shock despite 40 mL/kg fluid.
Dengue shock syndrome is likely a distinct entity from SS with some overlapping features. The DSS patients are significantly less likely to have systemic inflammatory response syndrome, be tachycardic, and have a narrower pulse pressure at admission when compared with SS patients. Mental status is better preserved, and spontaneous clinical bleeding is more common in children with DSS compared with those in SS. These likely results from the predominantly vasodilatory state in SS versus vasoconstrictory state that is the initial response in DSS.
The present paper describes the synthesis of a series of 8-(cyclopentyloxy)phenyl-xanthines and their evaluation for affinity for A1 and A2 adenosine receptors using radioligand binding assays. The effects of moving the cyclopentyloxy substituent with or without an ortho methoxy group on the various positions of the 8-phenyl ring have been studied. The vanilloid based xanthines 8-[4-(cyclopentyloxy)-3-methoxyphenyl]-1,3-dimethylxanthine (6a) (K(i)= 100 nM) and 8-[(4-cyclopentyloxy)-3-methoxyphenyl] -3-methyl-1-propylxanthine (12) (K(i) = 150 nM) displayed the highest affinity at A2A receptors as well as over 1000 fold selectivity over the A1 adenosine receptor subtype.
A new series of 1H-imidazol-1-yl substituted 8-phenylxanthine analogs has been synthesized to study the effects of the imidazole group on the binding affinity of compounds for adenosine receptors. Competition binding studies of these compounds were carried out in vitro with human cloned receptors using [(3) H]DPCPX and [(3) H]ZM 241385 as radioligands at A(1) and A(2A) adenosine receptors, respectively. The effect of the substitution pattern of the (imidazolyl)alkoxy group on various positions of the phenyl ring at C(8) was also studied. The xanthine derivatives displayed varying degrees of affinity and selectivity towards A(1) and A(2A) receptor subtypes despite a common but variedly substituted Ar-C(8).
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