In vitro Controlled Release from Solid Pharmaceutical Formulations of two new Adamantane Aminoethers with Antitubercular Activity (I).

The aim of the present investigation was to develop matrix tablet formulations for the in vitro controlled release of 2 new tuberculocidal adamantane aminoethers (compounds I and II), congeneric to the adamantane derivative SQ109, which is in final clinical trials, using carefully selected excipients, such as polyvinylpyrrolidone, sodium alginate and lactose. The tablets were prepared using the direct compression method and dissolution experiments were conducted using the US Pharmacopoeia type II apparatus (paddle method) in gastric and intestinal fluids. The results confirm that both analogues, albeit more lipophilic than SQ109, showed satisfactory in vitro release characteristics from solid pharmaceutical formulations. In conclusion, these formulations merit further assessment by conducting in the future bioavailability in vivo studies.

Detection of biofilm production of Yersinia enterocolitica strains isolated from infected children and comparative antimicrobial susceptibility of biofilm versus planktonic forms.

BACKGROUND AND OBJECTIVES: The ability of Yersinia species to produce biofilms has not been hitherto systematically studied, although there is evidence, that Y. enterocolitica is able to form biofilms on inanimate surfaces. The present study aimed to detect the production of biofilms by 60 clinical strains of Y. enterocolitica and to compare the antimicrobial susceptibility of planktonic versus biofilm-forming bacteria. METHODS: Y. enterocolitica strains were collected from stool and blood cultures collected from ß-thalassaemic children, with gastroenteritis and/or septicemia. The isolated bacterial strains were grouped by biotyping and serotyping and the antimicrobial susceptibility of the planktonic forms was investigated by MIC determination. Biofilm formation was detected by the use of silicone disks and for the biofilm forming strains the minimum inhibitory concentration for bacterial regrowth (MICBR) of 11 clinically important antimicrobials was determined. The presence of the waaE, a gene reported to be related with biofilm formation was investigated in all the strains. RESULTS: All of 60 strains were positive for biofilm production by the use of silicone disks. The great majority of the biofilm forms were resistant to all the antimicrobials. In antimicrobial concentrations far higher than the CLSI breakpoints, bacterial regrowth from the biofilms was still possible. None of the strains bore the waaE gene. CONCLUSIONS: These results, indicate that biofilm formation by Y. enterocolitica might be an inherent feature. The presence of biofilms increased dramatically the MICBR in all antimicrobials. The way in which biofilms could contribute to Y. enterocolitica pathogenicity in humans is a matter needing further investigation.

Pulmonary lactate release in patients with acute lung injury is not attributable to lung tissue hypoxia.

OBJECTIVE: To determine whether pulmonary lactate production in patients with acute lung injury is attributable to lung tissue hypoxia. DESIGN: Prospective, controlled, clinical study. SETTING: A multidisciplinary university intensive care unit in a general hospital. PATIENTS: Seventy consecutive critically ill patients requiring mechanical ventilation and invasive hemodynamic monitoring. Of these patients, 18 had no acute lung injury (no ALI); 33 had acute lung injury (ALI) (Lung Injury Score [LIS] < or =2.5); and 19 had acute respiratory distress syndrome (ARDS) (LIS >2.5). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After hemodynamic measurements, lactate and pyruvate concentrations were assessed in simultaneously drawn arterial (a) and mixed venous (v) blood samples. Pulmonary lactate release was calculated as the product of transpulmonary a-v lactate difference (L[a-v]) times the cardiac index. Two indices of anaerobic metabolism of the lung, i.e., the transpulmonary a-v difference of lactate pyruvate ratio (L/P[a-v]) and excess lactate formation across the lungs (XL), were calculated. L(a-v) and pulmonary lactate release were higher in patients with ARDS than in the other groups (p<.001), and they were also higher in patients with ALI compared with patients with no ALI (p<.001). In patients with ALI and ARDS (n = 52), pulmonary lactate release correlated significantly with LIS (r2 = .14, p<.01) and venous admixture (r2 = .13, p<.01). When all patients were lumped together (n = 70), pulmonary lactate release directly correlated with LIS (r2 = .30, p<.001), venous admixture (r2 = .26, p<.001), and P(A-a)O2 (r2 = .14, p<.01). Neither L/P(a-v) nor XL was significantly different among the three groups. CONCLUSION: The lungs of patients with ALI produce lactate that is proportional to the severity of lung injury. This lactate production does not seem to be attributable to lung tissue hypoxia.

Jaundice and bilirubin levels in Greek children with favism.

Jaundice and bilirubin levels varied widely in 85 children with favism. Low bilirubin levels (less than 2 mg/100 ml) with clinically undetectable jaundice were seen in 34 (40%), mild jaundice in 32 (38%), moderate in 16 (19%), and severe (greater than 8 mg/100 ml) in 3 (4%). Bilirubin levels were unrelated to the severity of anaemia or to reticulocytosis. The absence of bilirubinaemia and jaundice in a high proportion of the patients was attributed to the ability of the liver to conjugate large amounts of bilirubin. The extreme bilirubinaemia and jaundice observed in a minority of cases was attributed to the existence of an additional hereditary factor affecting the liver.