Blood Compatibility of Amphiphilic Phosphorous Dendrons-Prospective Drug Nanocarriers.

Dendrons are branched synthetic polymers suitable for preparation of nanosized drug delivery systems. Their interactions with biological systems are mainly predetermined by their chemical structure, terminal groups, surface charge, and the number of branched layers (generation). Any new compound intended to be used, alone or in combination, for medical purposes in humans must be compatible with blood. This study combined results from in vitro experiments on human blood and from laboratory experiments designed to assess the effect of amphiphilic phosphorous dendrons on blood components and model membranes, and to examine the presence and nature of interactions leading to a potential safety concern. The changes in hematological and coagulation parameters upon the addition of dendrons in the concentration range of 2-10 µM were monitored. We found that only the combination of higher concentration and higher generation of the dendron affected the selected clinically relevant parameters: it significantly decreased platelet count and plateletcrit, shortened thrombin time, and increased activated partial thromboplastin time. At the same time, occasional small-sized platelet clumps in blood films under the light microscope were observed. We further investigated aggregation propensity of the positively charged dendrons in model conditions using zwitterionic and negatively charged liposomes. The observed changes in size and zeta potential indicated the electrostatic nature of the interaction. Overall, we proved that the low-generation amphiphilic phosphorous dendrons were compatible with blood within the studied concentration range. However, interactions between high-generation dendrons at bulk concentrations above 10 µM and platelets and/or clotting factors cannot be excluded.

[Intravenous glutamine and early nasojejunal nutrition in severe acute pancreatitis -- a prospective randomized clinical study]. / Intravénás glutamin és korai nasojejunalis táplálás együttes alkalmazása súlyos acut pancreatitisben -- prospektív randomizált kettos vak kontrollált klinikai vizsgálat.

INTRODUCTION: Severe acute pancreatitis (SAP) is still one of the great challenges in gastro-intestinal surgery. According to recent studies, intravenously administered glutamine with total parenteral nutrition may be beneficial in the prevention of infectious complications and may reduce mortality rate. However, it has not been investigated yet, whether i.v. glutamine is able to achieve the same effect with early enteral nutrition as well. OBJECTIVES: The objective of our prospective randomized double-blind study was to explore the effects of intravenously administered glutamine with early nasojejunal nutrition in severe acute pancreatitis. PATIENTS AND METHODS: Forty-five patients with severe acute pancreatitis (with a Glasgow score at least 3 and/or a CRP level above 150 mg/ml on admission) were randomized into two groups. Group Glutamine (n = 24) was given 0.5 g/kg/die glutamine intravenously, while the control group (n = 21) received normal amino acid solution in the same quantity for 7 days. Nasojejunal nutrition was introduced 48 hours after admission in case of all patients, and their management was the same in every other aspect, too. The primary end-points of the study were the rate of pancreas-specific infectious complications and organ failure, and the secondary end-points were the necessity for radiological and surgical interventions, length of hospital stay and mortality rate. RESULTS: In group Glutamine, infected acute peripancreatic fluid collections (APFC) were detected in 4 patients, 2 patients had post-necrotic pancreatic/peripancreatic fluid collections (PNPFC), 2 patients had infected pseudocysts and 2 patients had walled-off pancreatic necrosis (WOPN). Ten patients were cured by ultrasound assisted puncture or drainage successfully. No surgical intervention was necessary. In the control group, 4 patients had infected APFC, 2 patients had infected PNPFC, infected pseudocysts and infected WOPN were diagnosed in 3 cases. Radiological intervention was effective in 9 cases, but 3 patients needed surgery. Three patients died of multi-organ failure, thus the mortality rate of the control group was 14%, while the mortality rate of the Glutamine group was zero. The mean hospital stay of the Glutamine group was 10.6 days, which is significantly shorter than the mean hospital stay of the control group, which was 15.9 days (p = 0.00104). DISCUSSION: The results of the Glutamine group are better in every end-points, however, statistically significant difference was detected in one parameter only, the length of hospital stay.

Alternative treatment modalities of infected pancreatic necrosis.

BACKGROUND/AIMS: Infected pancreatic necrosis diagnosed by fine needle aspiration (FNA) is generally considered an indication for surgery. Percutaneous drainage can postpone surgical intervention and in some cases can even have a therapeutic effect. Furthermore, targeted antibiotic therapy alone, based on bacterial cultures from FNA, can result in a full recovery. A retrospective analysis was carried out on the various treatment modalities of infected pancreatic necrosis. METHODOLOGY: Eighty patients with infected pancreatic necrosis were treated in the Department of Surgery, Teaching County Hospital, Györ, Hungary between 1998 and 2003. Seventy-four patients required surgical intervention, 12 of which underwent prior ultrasound or CT-guided drainage. RESULTS: In patients with previous percutaneous drainage the average time to first surgical intervention was 30 days (n=12). However, in those patients who did not undergo percutaneous drainage the time to initial surgical intervention was 15.6 days. This was statistically significant (p = 0.001). There was a full recovery in 3 out of the 15 patients, who underwent percutaneous drainage. This figure of 20% corresponds with that in the published literature. Three of the total 80 patients studied made a complete recovery when treated with targeted antibiotic therapy alone and did not require further radiological or surgical intervention. CONCLUSIONS: Our data indicate that percutaneous drainage can postpone surgical intervention. Furthermore, we demonstrate that percutaneous drainage alone can lead to full recovery in selected cases. In addition, targeted antibiotic therapy based on FNA may result in the complete recovery of a stable patient without requiring radiological or surgical intervention.

[Current possibilities in the treatment of infected pancreatic necrosis]. / A fertozött pancreas necrosis kezelésének korszeru lehetoségei.

This is a retrospective study about 80 patients treated for infected necrosis of the pancreas between 1998-2003. Operation was performed in 74 patients, diagnosis was achieved by CT or U.S. guided drainage in 12 patients. In further 6 patients drainage and antibiotic therapy provided cure. In patients who were drained pre-operatively (n=12) the first surgical intervention was performed on average on the 30.2 days after admission, while in the group of patients without drainage surgery became necessary after 15.6 days. The difference is statistically significant (p = 0.001). Our data proved that in certain cases percutaneous drainage can delay surgical intervention. Our results also prove that percutaneous drainage itself can lead to complete cure. In our own practice this stands for about 20% of our patients. In 3 patients we proved that if the patients general condition is stable infected necrosis detected by fine needle aspiration can be successfully treated by antibiotic therapy, without surgical or further radiological intervention.

Deletion of BGL2 results in an increased chitin level in the cell wall of Saccharomyces cerevisiae.

It is shown that the deletion of BGL2 gene leads to increase in chitin content in the cell wall of Saccharomyces cerevisiae. A part of the additional chitin can be removed from the bgl2Delta cell wall by alkali or trypsin treatment. Chitin synthase 1 (Chs1) activity was increased by 60 % in bgl2Delta mutant. No increase in chitin synthase 3 (Chs3) activity in bgl2Delta cells was observed, while they became more sensitive to Nikkomycin Z. The chitin level in the cell walls of a strain lacking both BGL2 and CHS3 genes was higher than that in chs3Delta and lower than that in bgl2Delta strains. Together these data indicate that the deletion of BGL2 results in the accumulation and abnormal incorporation of chitin into the cell wall of S. cerevisiae, and both Chs1 and Chs3 take part in a response to BGL2 deletion in S. cerevisiae cells.