Inhibitory effects of flavonoids on human immunodeficiency virus type-I integrase

One hundred and eighty-three flavonoids were screened for their inhibitory effects on HIV-l integrase (IN) using a multiplate integration assay (MIA). Of the tested flavonoids, 6-hydroxyluteolin, scutellarein, pedalitin, scutellarin, baicalein dimer, hypolaetin, 7-O-benzyl-6-hydroxyluteolin and baicalein showed appreciable inhibition with IC_ values of 0.4, 0.6, 1.3, 1.7, 2.0, 2.1, 3.0 and 3.6 μM, respectively. The potent inhibition was observed with flavonoids having at least one pair of vicinal hydroxyl groups and the activity was highly dependent on the number of vicinal hydroxyl groups. On the other hand, the inhibitory activity tended to be decreased by replacing a hydroxyl group with one of methoxyl, acetoxyl, isopropoxyl, isopentenyl, benzyloxyl, glucuronyl and glycosyl groups. No flavanones, flavanonols and chalcones examined in this experiment showed any significant inhibitory activity. マルチプレートインテグレーション法を用いて183種のフラボノイド類のHIV-1インテグラーゼ阻害効果を検討した。これらのうち6-hydroxyluteolin, scutellarein, pedalitin, scutellarin, baicalein二量体,hypolaetin,7-O-benzyl-6-hydroxyluteolinおよびbaicaleinは強い阻害を示し,それらの50%阻害濃度はそれぞれ0.4, 0.6, 1.3, 1.7, 2.0 ,2.1 ,3.0および3.6μMであった。フラボノイド類による阻害には少なくとも一対の隣接したヒドロキシル基が必要であった。また,隣接したヒドロキシル基の数が増加するに従い,HIV-1インテダラーゼ阻害活性も上昇した。他方,ヒドロキシル基がmethoxyl基, acetoxyl基, isopropoxyl基, isopentenyl基, benzyloxyl基, glucuronyl基 及びglycosyl基に置換されると阻害活性は減少あるいは消失した。試験したフラバノン,フラバノール,カルコン類には顕著な阻害活性は認められなかった

Hemorrhagic shock and encephalopathy syndrome – the markers for an early HSES diagnosis

<p>Abstract</p> <p>Background</p> <p>The hemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disease that affects young children. The outcomes of HSES patients are often fatal or manifesting severe neurological sequelae. We reviewed the markers for an early diagnosis of HSES.</p> <p>Methods</p> <p>We examined the clinical, biological and radiological findings of 8 patients (4 months to 9 years old) who met the HSES criteria.</p> <p>Results</p> <p>Although cerebral edema, disseminated intravascular coagulopathy (DIC), and multiple organ failure were seen in all 8 cases during their clinical courses, brain computed tomography (CT) scans showed normal or only slight edema in 5 patients upon admission. All 8 patients had normal platelet counts, and none were in shock. However, they all had severe metabolic acidosis, which persisted even after 3 hours (median base excess (BE), -7.6 mmol/L). And at 6 hours after admission (BE, -5.7 mmol/L) they required mechanical ventilation. Within 12 hours after admission, fluid resuscitation and vasopressor infusion for hypotension was required. Seven of the patients had elevated liver enzymes and creatine kinase (CK) upon admission. Twenty-four hours after admission, all 8 patients needed vasopressor infusion to maintain blood pressure.</p> <p>Conclusion</p> <p>CT scan, platelet count, hemoglobin level and renal function upon admission are not useful for an early diagnosis of HSES. However, the elevated liver enzymes and CK upon admission, hypotension in the early stage after admission with refractory acid-base disturbance to fluid resuscitation and vasopressor infusion are useful markers for an early HSES diagnosis and helpful to indicate starting intensive neurological treatment.</p