Lymphomas and acute abdomen - a set of case reports.

Surgical treatment of gastrointestinal solid tumors is the basic method with a curative potential. However, the first-line treatment modalities in lymphomas are systemic oncology therapy (chemotherapy, immunotherapy and hematopoietic stem cell transplantation), radiotherapy or their combination. Surgery in lymphomas is predominantly associated with acute disease and dominantly, surgery is still used mainly in diagnosing lymphomas. Acute abdomen associated with lymphoma can be divided into 3 groups: bleeding, obstruction and perforation of GIT due to lymphoma. All these conditions might be caused by both gastrointestinal (extranodal) lymphomas or advanced nodal lymphomas that directly infiltrate or compress gastrointestinal tract (GIT) as well. Perforation is also often associated with the effect of systemic chemotherapy administration. When treating acute abdomen conditions caused by lymphomas, multidisciplinary cooperation with all participating experts is necessary. From the surgical point of view, minimizing the risk of postoperative complications is crucial to ensure the possibility of early systemic oncological treatment administration.

Seven years of radionuclide laboratory at IMC - important achievements.

For many important research topics in polymer science the use of radionuclides brings significant benefits concerning nanotechnology, polymer drug delivery systems, tissue engineering etc. This contribution describes important achievements of the radionuclide laboratory at Institute of Macromolecular Chemistry of the Academy of Sciences of the Czech Republic (IMC) in the area of polymers for biomedical applications. Particular emphasis will be given to water-soluble polymer carriers of radionuclides, thermoresponsive polymer radionuclide carriers, thermoresponsive polymers for local brachytherapy, polymer scaffolds modified with (radiolabeled) peptides and polymer copper chelators for the therapy of Wilson´s disease.

Intracellular fate of polymer therapeutics investigated by fluorescence lifetime imaging and fluorescence pattern analysis.

Nanocarriers bearing anticancer drugs are promising candidates to improve the efficacy of cancer therapy and minimize side effects. The most potent cytostatics used in the treatment of various cancers are anthracyclines, e.g. doxorubicin or pirarubicin. Recently, polymer therapeutics carrying anthracyclines have been intensively studied. The precise characterization of in vitro nanocarrier biological behavior brings a better understanding of the nanocarrier characteristics and enables prediction of the behavior of the nanocarrier during in vivo application. Advanced fluorescence detection methods, e.g. fluorescence lifetime imaging microscopy (FLIM), were successfully exploited to describe the properties of various polymeric nano-systems and contributed to a complex view of anthracyclines' intracellular transport and DNA intercalation. Here, we report the application of a specific technique for processing FLIM images, called fluorescence pattern decomposition, to evaluate early events after doxorubicin or pirarubicin treatment of cells. Moreover, we characterized changes in the intracellular localization and release of the anthracyclines during the incubation of cells with polymer nanotherapeutics based on poly[N-(2-hydroxypropyl)-methacrylamide] (pHPMA).

Antioxidant Properties of 2-Hydroxyethyl Methacrylate-Based Copolymers with Incorporated Sterically Hindered Amine.

A series of model linear copolymers of 2-hydroxyethyl methacrylate (HEMA) and a sterically hindered amine derivative [N-(2,2,6,6-tetramethyl-piperidin-4-yl)methacrylamide (HAS)] were synthesized and characterized. Scavenging activities of the copolymers against reactive oxygen species (peroxyl and hydroxyl radicals) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals were determined. It was found that copolymers with medium HAS content (3.5-4.0 mol %) were better scavengers than copolymers with lower and higher HAS content and also than polyHEMA and polyHAS homopolymers and the HAS monomer. Importantly, these copolymers compared favorably even to established low-molecular weight antioxidant standards (BHA and dexpanthenol). Monomer reactivity ratios were determined, and the microstructure of the copolymers was assessed. Subsequently, cross-linked copolymers in the powder and film forms with optimal HAS content were synthesized. Their scavenging activities against the three types of radicals were determined, revealing that these hydrogels are potent scavengers of reactive oxygen species.

First-principles investigation of isomerization by proton transfer in beta-fumaric acid crystal.

Crystal structure of fumaric acid was investigated by Car-Parrinello molecular dynamics and Path Integral molecular dynamics. We propose a mechanism of isomerization by proton transfer in the solid state. It is shown that the three conformers of fumaric acid observed in cryogenic Ar matrix are also present in the solid. Standard ab initio Car-Parrinello dynamics of the studied solid at 100 K indicates that barrier height for proton transfer is too high to enable thermal jump over the barrier. Path Integral method in this particular case significantly changes proton behavior in the hydrogen bridge, and the proton tunneling process is observed. Vibrational spectra of investigated system HOOC-CH=CH-COOH and its deuterated analog DOOC-CH=CH-COOD were calculated and compared with experimental data.

Correlation of peripheral blood monocyte and neutrophil direct counts with plasma inflammatory cytokines and TNF-alpha soluble receptors in the initial phase of acute pancreatitis.

MATERIAL: The relationship between direct count of peripheral blood leucocyte populations and plasma concentrations of IL-6, IL-8, sTNFR-55 and sTNFR-75 during five initial days of acute pancreatitis was studied. RESULTS: Most significant relationship was found for monocytes, which correlated with sTNFR-55 (R = 0.38, p < 0.05) and sTNFR-75 (R = 0.41, p < 0.05 and R = 0.55, p < 0.01 during 1st and 2nd day, respectively). Later, in days 2, 3 and 4 an interrelation between monocytes and IL-6 (R = 0.49 to R = 0.41, p < 0.01) was observed. Monocytes also correlated with IL-8 in days 2 and 3 (R = 0.41, p < 0.05 and R = 0.43, p < 0.01, respectively). Neutrophil count correlated with IL-6 in days 3 and 4 (R = 0.34, p < 0.05 and R = 0.56, p < 0.01, respectively) and with IL-8 in the 4th day only (R = 0.39, p < 0.05). No significant correlations of lymphocyte, eosinophil and basophil direct counts with cytokines and receptors during the initial 5 days of AP were found. CONCLUSIONS: Observed relationships between monocyte direct counts and plasma cytokine levels reflect monocytes involvement in the development of acute pancreatitis.

Acute biliary pancreatitis in the era of minimally invasive surgery.

PURPOSE: Opinions about early endoscopic sphincterotomy and time of laparoscopic cholecystectomy in acute biliary pancreatitis are still controversial. Some authors reserved this procedure only for cases in which the stones were visualized during ERCP or patients had clinical symptoms of acute cholangitis. The aim was the assessment of the dynamic of changes of proinflammatory cytokines and white blood cells in time in patients with acute biliary pancreatitis after performed endoscopic sphincterotomy and laparoscopic cholecystectomy. MATERIAL AND METHODS: We enrolled 43 consecutive patients with clinically diagnosed mild forms of acute biliary pancreatitis. All were treated by early endoscopic sphincterotomy and laparoscopic cholecystectomy performed during the first 48 hours after admission. The course of the disease was monitored by measurement of the level of proinflammatory cytokines. RESULTS: Marked decrease of the level of proinflammatory interleukins within 24 hours after endoscopic sphincterotomy was observed. Mean values of IL-6 and IL-8 were statistically lower immidiately after this procedure (p < 0.001). Subsequent decrease was achieved after laparoscopic cholecystectomy. The mean values of TNF-alpha and IL-12p40 were relatively constant throughout the study period. CONCLUSION: All patients suffering from mild acute biliary pancreatitis should be treated by using minimally invasive procedures. However, such a only treatment should be reserved for experienced centers.

Early endoscopic sphincterotomy and early laparoscopic cholecystectomy in the treatment of severe acute biliary pancreatitis--a preliminary report.

PURPOSE: The proper timing of endoscopic sphincterotomy and laparoscopic cholecystectomy in acute biliary pancreatitis is still a subject of controversies. The following rapid report presents preliminary data concerning treatment of patients with severe form of necrotizing biliary pancreatitis (SNBP) with the sequence of minimal invasive procedures (endoscopic sphincterotomy and laparoscopic cholecystectomy) performed in the first 48 hours after admission. MATERIAL AND METHODS: Twelve patients with SNBP were included in the study. The described above procedures were performed in all of the patients within 48 hours. We evaluated clinical outcome, complications, time of stay in hospital and also some morphological (white blood cells) and liver parameters (AST, ALT, bilirubin, ALP and GGT) of these patients in the course of the disease. RESULTS: Two patients died. Two other ones has local complications. We did not observe major complications after ERCP with ES and after laparoscopic cholecystectomy. Additionally, the lavage of the abdominal cavity was performed and drainage was established during laparoscopic cholecystectomy. Conversion in our group occurred in 1 person. Later complications in the course of the disease were caused by the its progression and not related to the performed procedures. CONCLUSIONS: The results are very incurable, however, performing these types of procedures in the experienced centers deserves to be taken into account.

Poly-C specific ribonuclease activity correlates with increased concentrations of IL-6, IL-8 and sTNFR55/sTNFR75 in plasma of patients with acute pancreatitis.

Plasma pancreatic-type Poly-C specific ribonuclease (P-RNase)-enzyme activity increases in patients with acute pancreatitis (AP) who develop pancreatic necrosis and severe disease course. It is considered as a marker of pancreatic tissue destruction. The aim of this study was to estimate interrelations between major inflammatory cytokines such as: interleukin 6 (IL-6), interleukin 8 (IL-8) and tumor necrosis factor soluble receptors: sTNFR55 and sTNFR75 output, and plasma P-RNase activity. The study was carried out in a group of 56 patients with AP, where 20 developed pancreatic necrosis. It was found that serum P-RNase concentration and levels of all studied inflammatory cytokines significantly increase already in the first day from diagnose of the disease (2.5 folds for P-RNase, 20 for IL-8, about 200 for IL-6 and 1.5 for receptors, respectively). In the first day from admission to hospital, P-RNase activity significantly correlated with plasma concentration of studied inflammatory cytokines. The most pronounced correlation was found for P-RNase and IL-6 in days 1-4 from diagnose, manifested by Pearson correlation r coefficients amounting to 0.86, 0.79, 0.60 and 0.57 respectively (p<0.001). Dividing the studied AP patients into two groups, varying in severity of disease a significant differences in P-RNase and IL-6, IL-8 and sTNFR55/sTNFR75 were found. In patients with acute necrotizing pancreatitis P-RNase significantly correlate with levels of major inflammatory cytokines. Carried out studies suggest that activity of P-RNase reflects severity of inflammatory reaction, which is dependent on development of pancreatic injury and tissue necrosis in AP.

Stereoselective synthesis of functionalized trisubstituted olefins via palladium(0)-catalyzed cross-coupling reaction.

[reaction: see text]. A highly flexible and stereoselective protocol for the synthesis of branched (E)- and (Z)-trisubstituted alkenes has been developed. The key steps are hydrozirconation-iodination of (1-alkynyl)trimethylsilane followed by Negishi-type cross-coupling. The resultant (Z)-vinyl silane is iododesilylated and subjected to a second cross-coupling reaction to give the trisubstituted olefin. Model studies aimed at the construction of the C14-C15 (Z)-trisubstituted olefin of discodermolide and the C8-C9 (Z)-trisubstituted olefin of callystatin A and analogues are also described.

Composition of free fatty acid and triglyceride fractions in human necrotic pancreatic tissue.

BACKGROUND: Lipolytic enzymes, such as lipase, phospholipase A(2), lipoprotein lipase, and hormone-sensitive adipocyte lipase are probably implicated in the pathogenesis of acute pancreatitis. The increased activity of these enzymes can cause specific changes in fatty acid composition, both to free fatty acid (FFA) and triglyceride (TG) fractions in necrotically changed pancreatic tissue. MATERIAL AND METHODS: Specimens of necrotically changed pancreatic tissue taken intraoperatively from 13 patients operated for serious necrotic acute pancreatitis were analysed. The Fölsch extraction method and separation of lipids by thin-layer chromatography was used, and the final fatty acid composition was determined after methylation by gas liquid chromatography. RESULTS: The changes in the FFA fraction are more definite than those for the triglyceride fraction and refer mostly to the increased percentage distribution of unsaturated fatty acids. CONCLUSIONS: These studies lead to the hypothesis that fatty acids released in the process of lipolysis play a key role in the pathogenesis of acute pancreatitis.

Red cell deformability in patients with chronic atheromatous ischemia of the legs.

BACKGROUND: It has been shown that atherosclerosis can cause not only lowering of the perfusion pressure gradient at the macro/micro circulation level, but can bring about untoward rheological changes such as e.g. loss of the red blood cells (RBC) elasticity. This can participitate in mechanism of impairment of the blood flow through the microcirculation as well. The aim of this study was to measure RBC elasticity in the claudicants, and to evaluate the effect of the applied treatment either conservative or surgical revascularisation on this rheological parameter. MATERIAL AND METHODS: RBC deformability was examined in claudicants 83 of them (mean claudication distance 400 m) were treated conservatively (walking exercise on a treadmill and Pentoxyphilline 600 mg b.i.d.) 44 claudicants with the critical leg ischemia (mean claudication distance below 50 m or rest pain) underwent surgical revascularisation. The measurements of RBC elongation (under selected values of the shear stress) were made on entry to the study, after 6 weeks, and 12 weeks of observation. RESULTS: After 12 weeks of conservative treatment, RBC elasticity both at rest and after walking exercise significantly increased. In the patients undergoing surgery mean RBC elasticity both at rest and after walking exercise 12 weeks following surgery was not significantly different compare with the respective levels at the beginning of the study. CONCLUSIONS: In the group of claudicants with less advanced atherosclerosis (conservative group), the treatment brought about significant increase of RBC elasticity. On the contrary in case of the patients with advanced atherosclerosis and critical leg ischemia revascularisation alone appeared to be ineffective in correction of untoward rheologic alteration such as rigidity of the erythrocytes.

Enhanced diastereoselectivity in asymmetric crotylation reactions using propargylic dicobalt hexacarbonyl complexes.

[reaction: see text] Hexacarbonyl dicobalt complexes of propargylic acetals undergo Lewis acid catalyzed crotylation reactions with enhanced levels of diastereoselectivity (dr 6 to >20:1, syn/anti) while efficiently producing stereochemically well-defined homoallylic ethers. These results are in contrast to uncomplexed propargylic acetals, which undergo the crotylation reactions with low selectivity (dr < 2:1, syn/anti). After removal of the cobalt complex, the reactions afford propargylic ethers in high yields.

[Thyroid crisis diagnosed on the basis of anatomic-pathologic examination]. / Przelom tarczycowy rozpoznany na podstawie badania anatomopatologicznego.

Graves-Basedow disease is the most common cause of hyperthyroidism. Rhabdomyolysis is occasionally associated with metabolic coma or severe electrolyte disturbances. We describe rhabdomyolysis accompany ing thyroid crisis. A 48-years old man admitted with hypovolemic shock developed rhabdomyolysis, congestive heart failure, hepatic failure and renal failure and then died. It is interesting that correct diagnosis was done on the basis of microscopic examination of specimens of the thyroid gland.

Formal [4+2]-annulation of chiral crotylsilanes: synthesis of the C19-C28 fragment of phorboxazoles.

A stereoselective synthesis of the C19-C28 fragment of phoborxazole A and B is described. The key step is an enantioselective [4 + 2]-annulation of a crotylsilane 10 with a propargylic aldehyde 11 affording a functionalized dihydropyran 12. A solvent-dependent stereoselective epoxidation of dihydropyrans is also documented.

Total synthesis of rutamycin B and oligomycin C.

The asymmetric synthesis of the macrolide antibiotics (+)-rutamycin B (1) and (+)-oligomycin C (2) is described. The approach relied on the synthesis and coupling of the individual spiroketal fragments 3a and 3b with the C1-C17 polyproprionate fragment 4. The preparation of the spiroketal fragments was achieved using chiral (E)-crotylsilane bond construction methodology, which allowed the introduction of the stereogenic centers prior to spiroketalization. The present work details the synthesis of the C19-C28 and C29-C34 subunits as well as their convergent assembly through an alkylation reaction of the lithiated N,N-dimethylhydrazones 6 and 8 to afford the individual linear spiroketal intermediates 5a and 5b, respectively. After functional group adjustment, these advanced intermediates were cyclized to their respective spiroketal-coupling partners 40 and 41. The requisite polypropionate fragment was assembled in a convergent manner using asymmetric crotylation methodology for the introduction of six of the nine-stereogenic centers. The use of three consecutive crotylation reactions was used for the construction of the C3-C12 subunit 32. A Mukaiyama-type aldol reaction of 35 with the chiral alpha-methyl aldehyde 39 was used for the introduction of the C12-C13 stereocenters. This anti aldol finished the construction of the C3-C17 advanced intermediate 36. A two-carbon homologation completed the construction of the polypropionate fragment 38. The completion of the synthesis of the two macrolide antibiotics was accomplished by the union of two principal fragments that was achieved with an intermolecular palladium-(0) catalyzed cross-coupling reaction between the terminal vinylstannanes of the individual spiroketals 3a and 3b and the polypropionate fragment 4. The individual carboxylic acids 46 and 47 were cyclized to their respective macrocyclic lactones 48 and 49 under Yamaguchi reaction conditions. Deprotection of these macrolides completed the synthesis of the rutamycin B and oligomycin C.

Carbon dioxide and water vapor exchange by young and old ponderosa pine ecosystems during a dry summer.

We investigated key factors controlling mass and energy exchange by a young (6-year-old) ponderosa pine (Pinus ponderosa Laws.) plantation on the west side of the Sierra Nevada Mountains and an old-growth ponderosa pine forest (mix of 45- and 250-year-old trees) on the east side of the Cascade Mountains, from June through September 1997. At both sites, we operated eddy covariance systems above the canopy to measure net ecosystem exchange of carbon dioxide and water vapor, and made concurrent meteorological and ecophysiological measurements. Our objective was to understand and compare the controls on ecosystem processes in these two forests. Precipitation is much higher in the young plantation than in the old-growth forest (1660 versus 550 mm year-1), although both forests experienced decreasing soil water availability and increasing vapor pressure deficits (D) as the summer of 1997 progressed. As a result, drought stress increased at both sites during this period, and changes in D strongly influenced ecosystem conductance and net carbon uptake. Ecosystem conductance for a given D was higher in the young pine plantation than in the old-growth forest, but decreased dramatically following several days of high D in late summer, possibly because of xylem cavitation. Net CO2 exchange generally decreased with conductance at both sites, although values were roughly twice as high at the young site. Simulations with the 3-PG model, which included the effect of tree age on fluxes, suggest that, during the fall through spring period, milder temperatures and ample water availability at the young site provide better conditions for photosynthesis than at the old pine site. Thus, over the long-term, the young site can carry more leaf area, and the climatic conditions between fall and spring offset the more severe limitations imposed by summer drought.

Response of stomatal conductance to drought in ponderosa pine: implications for carbon and ozone uptake.

To gain insight into the limitations imposed by a typical Mediterranean-climate summer drought on the uptake of carbon and ozone in the ponderosa pine (Pinus ponderosa Dougl. ex Laws.) ecosystem, we compared diurnal trends in leaf physiology of young trees in a watered and a control plot located in the Sierra Nevada Mountains, CA, USA (Blodgett Forest, 38 degrees 53' N, 120 degrees 37' W, 1315 m elevation). Predawn water potential of trees in the watered plot remained above -0.3 MPa throughout the growing season, whereas it dropped in the control plot from -0.24 to -0.52 MPa between late May and mid-August. Photosynthesis and stomatal conductance of trees in the watered plot were relatively insensitive to atmospheric vapor pressure deficit (VPD), whereas gas exchange of trees in the control plot varied with changes in soil water, VPD and temperature. Although the 1998 growing season was abnormally wet, we saw a pronounced drought effect at the control site. Over the 2 months following the onset of watering, carbon and ozone uptake were measured on three days at widely spaced intervals. Carbon uptake per unit leaf area by 1-year-old foliage of trees in the control plot was 39, 35 and 30% less, respectively, than in the watered plot, and estimated ozone deposition per unit leaf area (ozone concentration times stomatal conductance) was 36, 46 and 41% less.

Serum free fatty acid concentration in patients with acute pancreatitis.

BACKGROUND: The involvement of lipolytic enzymes and liberated fatty acids in ethiology of acute pancreatitis (AP) has been implicated. AIM: To analyze the level of FFA in the patients with AP in relation to severity of the disease. MATERIAL AND METHODS: The study included 36 patients with acute edematous AP (group I), 29 patients with necrotizing AP: 16 without (group IIA) and 13 with complications (group IIB), and 12 control subjects. Serum levels of total FFA (by enzymatic method) and the individual fatty acids of the FFA pool (by gas-liquid chromatography) were measured during the first 4 days after admission. RESULTS: A significant increase in the mean total serum FFA was noted for all the groups with the highest values on admission (p < 0.02-0.01). The per cent contribution was significantly higher as compared to control group for oleic acid (group I, p < 0.02, group IIA, p < 0.05, group IIB, p < 0.005), linoleic acid (group IIB, p < 0.02) and arachidonic acid (group IIA, p < 0.05, group IIB, p < 0.02). Significantly lower percentage was noted for stearic acid (all three groups: p < 0.01, p < 0.005, p < 0.01, respectively) and for palmitic acid (only group IIB: p < 0.005). The ratio of saturated to polyunsaturated fatty acids was significantly lower than in control group on each day of study for group IIB only (p < 0.005-p < 0.001). CONCLUSION: Polyunsaturated fatty acids, mainly linoleic and arachidonic, may be involved in the development of complications in acute pancreatitis.

An asymmetric aminohydroxylation approach to the azepine core of (-)-balanol.

[reaction: see text]An efficient formal synthesis of the potent protein kinase C inhibitor (-)-balanol that relies on a modified asymmetric aminohydroxylation of the alpha,beta-unsaturated aryl ester (1) is reported. The aryl ester functionality and the dihydroquinyl alkaloid ligand system (DHQ)2-AQN are used to control the regio- and enantioselectivity of the process.