Some new derivatives of thiosemicarbazide and the 1,2,4-triazole of sulphanylacetic acid have been chromatographed on RP-18 HPTLC plates with mobile phases containing water and an organic modifier (methanol, dioxane, acetone, 2-propanol, or tetrahydrofuran).Relationships between solute retention and modifier concentration were described by Snyder's linear equation.The equation was used to determine R M 0 values, by extrapolation, and the S values denoting the slopes of the relationship between linear retention and mobile phase concentration; both values characterize the lipophilicity of the substances.Calculated values of R M 0 were correlated with log P values for the drugs investigated by use of the software HyperChem.Correlations between intercept (R M 0 ) and slope (S) from the linear equations were also calculated.The effects of different mobile phase modifiers on experimentally obtained lipophilicity were also analysed and compared.

AbstractDie Bewertung der Entkeimungsleistung keimarm oder steril arbeitender Abfüllanlagen im Lebensmittel‐ und Pharmabereich erfolgt praktisch durch mikrobiologische Validierungsverfahren. Grundlage bei der Validierung sind Bioindikatoren mit ausgewählten Testkeimen, deren Resistenzen je nach Anzucht variieren und maßgeblich die Abtötungseffizienz beeinflussen können. Für eine reelle Aussage über das Wirkungsspektrum von Entkeimungsvorrichtungen sind deshalb definierte Resistenzen der Testkeime unerlässlich, die im Rahmen standardisierter Untersuchungsmethoden eingesetzt werden. In Abhängigkeit der verwendeten Testmethodik sind dabei neben der erreichbaren Keimreduktion auch Aussagen über die Praxistauglichkeit und den Hygienestatus des gesamten Abfüllprozesses möglich.

INTRODUCTION:Acute pancreatitis is a disease involving pro-inflammatory mediators. Two complex and multifactorial pathogenetic ways lead to edematous or necrotizing pancreatitis. The course of the disease is thought to be the consequence of an acute inflammatory response.AIM:The authors examined the impact of Escherichia coli LPS on the acute cerulein pancreatitis in rats.METHODS:The study was performed on rats using the ceruleine pancreatitis model. The activation status of polymorphonuclear cells, blood IL-6 concentration, oxidative stress parameters, pancreatic enzymes concentration and microscopic alterations were determined at 5th and 9th h observations.RESULTS:In acute pancreatitis and acute pancreatitis with LPS groups, the peripheral polymorphonuclear cells activity was lower than in control one. Authors noticed the same neutrophil activation in acute pancreatitis after lipopolysaccharide administration although the peripheral blood polymorphonuclear cells count was significantly higher at the 9th h observation. LPS neither changed the oxidative stress within pancreatic gland, nor amylase or serum lipase activity. LPS given to acute pancreatitis animals resulted in significant increase of serum IL-6 concentration at 5th observation turning normal after 9th h.CONCLUSIONS:Collected data supports thesis of early polymorphonuclear cells involvement in acute pancreatitis and oxidative stress evidence in pancreatic parenchyma. However, results did not reveal that administration of LPS amplified inflammatory response during the course of acute pancreatitis.

Polymorphonuclear cells (PMN) activation is an essential step in acute pancreatitis (AP). We investigated the activation status of PMN, oxidative stress and pancreatic damage in early stage of experimental ceruleine pancreatitis in rats. The PMN action was modulated by monoclonal antibody CD 11b administration. The circulating WBC and polymorphonuclear cells count was reduced after AP induction. Chemiluminescence of whole blood PMN was remarkably reduced in AP group and increased after MoAb CD 11b administration. The CD 11b blockade significantly reduced the WBC infiltration and malondialdehyde (MDA) concentration within pancreatic gland. These data suggest that activated PMN are an important factor in early AP pathogenesis. Neutrophil aggregation within pancreatic gland modulated by monoclonal antibody CD11b contribute to the extent of injury during the early stage of ceruleine experimental pancreatitis in rats.

The Lichtenstein hernioplasty has become a popular method in inguinal hernia repair. This study compared two methods of mesh fixation and wound closure. Forty-six men with unilateral inguinal hernia were randomized into two groups. In the control group polypropylene mesh was anchored with 3/0 Dexon sutures, fascia and skin were closed with sutures 3/0 Dexon and 3/0 Monosof. In the study group, the mesh was secured with butyl-2-cyanoacrylate adhesive and the fascia and skin were also glued with the adhesive. The costs of materials, duration of the operation, amount of postoperative analgesic doses, pain score after the first and the 7th postoperative day and return to daily activity were recorded. No recurrences during the mean follow-up of 4.7 months were observed and the cosmetic effect was very good. In the study group with tissue adhesive the patients had significantly lower pain score after the first postoperative day and had a tendency to require less analgetic doses and to return earlier to their daily activity. Duration of the operation was similar in both groups. The cost of sutures and tissue adhesive used in both procedures was comparable. The use of tissue adhesive in mesh fixation and wound closure seems to be a promising technique in Lichtenstein hernia repair.

Endoscopic polypectomy is a standard method of treatment of gastrointestinal polyps, but is associated with substantial risk of complications. The most common is hemorrhage, the rate of which varied between 0.3%, and 6%. Various prophylactic techniques have been used to reduce this incidence. The aim of this study was to establish whether the prophylactic injection of adrenaline–saline solution reduces the risk of postpolypectomy bleeding in colonoscopic polypectomy.

Pancreatic fistula is a rare postoperative complication, usually occurring after pancreatic surgery. Majority of them heal spontaneously, some patients require somatostatin/octreotide treatment. The authors have presented 11 patients with postoperative pancreatic fistula, in whom octreotide therapy in dose of 0.1 mg t.i.d./10 days has been ineffective. The causes of pancreatic fistula have been as follows: necrosectomy of the infected pancreatic necrosis--5 patients, distal pancreatic resection--2 patients, insulinoma enucleation--2 patients, gastrectomy with partial pancreatectomy--2 patients. In 9 patients endoscopic stenting of the main pancreatic duct has been performed. In remained 2 patients after Roux-en-Y gastrectomy the endoscopic access to Vater papilla has been impossible and the patients have received one intramuscular injection of long acting somatostatin analogue. In 8 of 9 patients with pancreatic stenting and in two patients after gastrectomy the fistula has been closed within the period of 6-17 days. In one patient after the necrosectomy the prosthesis implacement has been ineffective. This patient has been successfully treated with two additional injections of long acting somatostatin analogue (one injection/14 days). Authors have concluded that endoscopic pancreatic stenting has been an effective method of treatment of the postoperative pancreatic fistula, resistant to octreotide therapy. In some cases, additional administration of long acting somatostatin analogue has been necessary.

Abstract Background Twenty-six cases of infected pancreatic necrosis (IPN) treated by means of operation in the years 1997–1999 are presented. Methods The diagnosis of IPN was established before surgery by means of contrast-enhanced computed tomography and fine-needle aspiration of the infected pancreatic and peripancreatic tissue. Microbiological findings of infected tissue most commonly showed Escherichia coli (12) and Klebsiella pneumoniae (eight). Candidiasis was observed in three cases. All patients were stratified according to Acute Physiology and Chronic Health Evaluation (APACHE) II score within 24 h of admission to the ward and before planned surgery. Wide surgical exploration of the omental sac and retroperitoneal space, gentle necrosectomy of necrotic tissue, and continuous omental sac lavage in connection with an ‘open abdomen’ technique was carried out within 4–22 (mean 10) days from the onset of the disease. Planned relaparotomies were performed every 4–5 days until all the necrotic tissue was removed and granulation of the operating area was observed. Closure of the abdomen was performed within 14–34 (mean 23) days after primary laparotomy. Results Six patients died (mortality rate 23 per cent) during the postoperative period from multisystem organ failure accompanying septic shock. The poor outcome was related to a high APACHE II score (11–15). During the postoperative period the following complications were observed: respiratory insufficiency requiring mechanical ventilation (24 cases), colonic fistula (five), pancreatic fistula (three), renal insufficiency requiring haemofiltration (three), upper gastrointestinal bleeding (two) and gastric fistula (one). Incisional hernia developed in five patients who left hospital. The hospital stay for survivors ranged between 26 and 52 (mean 36) days. Conclusion Diagnosis of IPN based on dynamic computed tomography and bacteriological examination of necrotic aspirate and the consecutive surgical treatment, including wide repeated necrosectomy and continuous lavage combined with an ‘open abdomen’ technique, is the management of choice, and may improve the results of treatment.

The aim of this study was to investigate the impact of L-arginine (nitric oxide synthase substrate), L-NG-nitro-L-arginine (nitric oxide synthase inhibitor), and heparin on the pancreas microcirculation, serum IL-6 level and microscopic alterations of the pancreas in acute pancreatitis in rats. Acute pancreatitis was induced by 4 i.p. injections of cerulein (15mg/kg). Microcirculatory values were measured by means of laser Doppler flowmetry 5 h after the first cerulein injection. Remarkable histopathological changes in the pancreas, including parenchymal necrosis, an elevation of serum IL-6 level, and a significant drop of pancreatic capillary perfusion was observed in rats with nitric oxide synthase inhibition. L-arginine improved the pancreatic microcirculation but worsened the microscopic alterations within the pancreas. Heparin had a beneficial effect on the microcirculatory values, serum IL-6 concentration, and morphologic changes. Authors conclude that inhibition of nitric oxide synthase aggravates acute pancreatitis. L-arginine treatment improves pancreatic perfusion but potentiates morphological alterations. Heparin, improving the microcirculation and inflammatory changes within the pancreatic gland, may be considered as a promising therapeutic agent in acute pancreatitis.

A prospective randomized trial involving 30 patients was performed to assess whether second-look endoscopy could improve the efficacy of injection therapy for bleeding peptic ulcers. The inclusion criteria were the presence of active arterial bleeding or a non-bleeding visible vessel at emergency endoscopy. All the patients received emergency injection of thrombin with adrenaline solution and were subsequently randomized (15 patients in each group). All the patients receive a second elective endoscopy within the first 24 hours with repeated injection of thrombin-adrenaline solution (Group I) or fibrin sealant-Beriplast-(Group II). A tendency towards better results was noted in the Group II. Recurrent bleeding was observed in 6.6% versus 26.6% patients in Group I. The need for emergency surgery occurred in (6.6% in Group I versus 0 in Group II) and length of hospital stay was (13.2 in Group I versus 7.4 in Group II [p < 0.05]). No mortality was observed in both of the groups. In conclusion, our data suggest the possibility of a small benefit with second-look endoscopy with repeated injection of fibrin sealant.

Local microcirculatory dysfunction within the pancreatic gland might be an important factor in the conversion of oedematous to necrotizing pancreatitis. Therapeutic agents, improving the pancreatic blood flow, might be valuable in acute pancreatitis treatment. An influence of nitric oxide, heparin and procaine treatment on microcirculatory values in acute pancreatitis (AP) in rats was investigated. Acute pancreatitis was induced by i.p. injection of cerulein in four doses of 15 μg kg−1each at 1-h intervals. The rats with pancreatitis were divided into five groups, 12 animals each. One group remained without treatment, four groups were treated i.p. either with NO synthase inhibitorl-NNA (2×25 mg kg−1or heparin 2×2.5 mg kg−1orl-arginine 2×100 mg kg−1or procaine 2×25 mg kg−1. Five control groups, ten animals each, received saline,l-NNA, heparin,l-arginine or procaine only. Five hours after the first ceruleine injection microcirculatory values within the pancreas were measured by means of laser Doppler flowmetry. Acute pancreatitis caused a significant drop of microcirculatory value to 37% of the basal value. Thel-NNA administration resulted in a further insignificant reduction of the pancreatic blood flow to 34%. An improvement of microcirculation was observed in rats with pancreatitis receiving heparin (76%) andl-arginine (72%). Procaine had no effect on microcirculatory disturbances within the pancreas in rats with pancreatitis. Cn-induced acute pancreatitis (AP) causes microcirculatory deterioration within the pancreas. Heparin and nitric oxide donor,l-arginine, might be considered as therapeutic agents, improving the diminished pancreatic tissue perfusion observed in acute pancreatitis. Procaine does not improve the pancreatic blood flow in acute pancreatitis.

Microcirculatory disturbances of the colon may contribute to the pathogenesis of inflammatory bowel disease. The aim of the study was to investigate the alterations of rectal blood perfusion in experimental colitis with reference to nitric oxide and heparin treatment. The study was carried out on 36 rats, divided into six groups: group I, control; group II, control + NG-nitro-L-arginine (L-NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis was induced by 4% acetic acid enema, and 48 h after the enema, besides the measurement of rectal capillary blood flow by means of laser Doppler flowmetry, the serum interleukin-6 (IL-6) level and histopathological alterations within the rectal mucosa were examined. Experimental colitis resulted in a drop in rectal wall perfusion. L-Arginine and heparin treatment improved the microcirculatory values. The highest IL-6 level and the most advanced histopathological alterations were observed in the rats treated with L-NNA. L-Arginine treatment had no influence on IL-6 concentration, however it aggravated the inflammatory changes within the rectal mucosa. Heparin administration reduced the IL-6 values and also had a positive impact on the microscopic alterations within the rectal wall. It is concluded that heparin treatment has a beneficial effect on the microcirculatory disturbances and inflammatory changes observed in experimental colitis. The inhibition of nitric oxide-synthase aggravated the course of experimental colitis. L-Arginine administration improves the rectal blood flow but aggravates the histopathological alterations within the rectal wall.

The aim of the study was to investigate the potential role of nitric oxide (NO) on the microcirculation in experimental acute pancreatitis in rats. Twenty-five rats were divided into the following groups: group A (5 rats) = control; group B (5 rats) = acute pancreatitis induced by retrograde taurocholate infusion into the pancreatobiliary duct without treatment; group C (5 rats) = acute pancreatitis treated with the NO donor L-arginine; group D (5 rats) = acute pancreatitis treated with the NO synthase inhibitor N-nitro-L-arginine (L-NNA); group E (5 rats) = without pancreatitis receiving L-NNA. The animals were observed throughout 4 h. The microcirculatory values of the pancreas, liver, colon, stomach and kidney were measured by means of laser Doppler flowmetry. Three animals of group D died after the third hour of the experiment. In rats with pancreatitis, a rapid decrease in microcirculatory values was observed. The most pronounced drop in capillary blood flow within all the organs was observed in rats treated with the NO synthase inhibitor L-NNA, L-arginine administration in rats with acute pancreatitis slightly improved the microcirculatory values, although the improvement was significant in colon perfusion only. We conclude that NO may have a beneficial influence on the capillary organ perfusion in acute pancreatitis. The administration of an NO synthase inhibitor seems to have a detrimental effect on acute pancreatitis.

One hundred and ninety-one patients who had emergency endoscopy performed for acute gastroduodenal haemorrhage and were found to be bleeding actively (N = 141) or to have an ulcer containing a non-bleeding visible vessel (N = 50) were studied. Patients with active bleeding were divided into two groups: group I included 47 patients in whom diagnostic endoscopy was performed and conventional management applied; and group II contained 94 patients in whom, apart from conventional treatment, endoscopic thrombin injections could also be offered. Fifty patients with non-bleeding visible vessels were admitted to a prospective randomised trial and assigned to either endoscopic injections (group A, N = 25), or no primary endoscopic treatment (group B, N = 25). The introduction of the injection therapy in patients who were actively bleeding resulted in a significant reduction of the emergency operation rate (70.2% v. 12.8%; P < 0.001), mortality rate (21.3% v. 8.5%; P < 0.05 and blood transfusion requirements (4,220 +/- 1,840 ml v. 1,980 +/- 980 ml; P < 0.05). Endoscopic thrombin injections of non-bleeding visible vessels reduced the rebleeding rate (40% v. 4%; P < 0.01) and blood transfusions (2,939 +/- 1070 ml v. 1,390 +/- 552 ml; P < 0.05).

The main subject of considerations is acute necrotizing pancreatitis, based on the authors opinion and literature. Frequency of the necrosis in acute pancreatitis is established in between 7-15%. Because of very severe and often lethal complications these patients need special surgical attention. Enhanced CT is the most valuable diagnostic procedure to visualize the extend of pancreatic necrosis. There is no common agreement upon the mode of treatment except from that infected necrotizing pancreatitis should be operated. Indications for surgical treatment with particular analysis to necrosectomy and laparostomy is discussed.

Acute pancreatitis was induced in 13 anesthetized dogs by retrograde injection of bile mixed with trypsin into the pancreatic duct. Six animals were treated with intravenous infusion of new synthetic antiprotease, Nafamostat Mesilate, at a dose of 1 mg/kg/h. Four out of seven untreated animals died during the experiment. All the treated dogs survived. Hemodynamic data were regularly monitored during a ten-hour observation period. Cardiac output, mean arterial pressure and left ventricular stroke volume decreased rapidly in the untreated animals. An increase in systemic vascular resistance and pulmonary vascular resistance was observed in dogs without treatment. Nafamostat Mesilate given as therapy significantly improved the hemodynamic parameters, and prevented the animals from developing shock. The study demonstrates an advantageous influence of synthetic antiprotease Nafamostat Mesilate on the course of acute experimental pancreatitis.

Acute pancreatitis was induced in 19 anesthetized dogs by retrograde injection of bile mixed with trypsin into the pancreatic duct. Two groups, of six animals each, were treated with intravenous infusion of synthetic antiproteases: gabexate mesilate and nafamostat mesilate in doses of 1 mg/kg per hr. One group of seven animals remained untreated. Two untreated dogs died during the experiment. All the treated dogs survived. Hemodynamic data were monitored hourly during a 6-hr observation period. In the untreated animals, cardiac output, mean arterial pressure, and left ventricular stroke volume decreased rapidly; an increase of pulmonary vascular resistance and systemic vascular resistance was observed. Synthetic antiproteases, given as a therapy, improved the hemodynamic parameters significantly and prevented the animals from developing shock. Gabexate mesilate and nafamostat mesilate seem to be of value in the treatment of experimentally produced acute pancreatitis in dogs.

Acute pancreatitis was induced in ten anesthetized dogs by retrograde injection for bile mixed with trypsin into the pancreatic duct. Five animals were treated with i.v. infusion of gabexate mesilate in a dose of 1 mg/kg per hour. Hemodynamic data were regulary monitored during a 10-h observation period. Cardiac output (CO), mean arterial pressure (MAP), and left ventricular stroke volumne (LVSV) decreased rapidly in untreated animals. An increase of systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) was observed in dogs without treatment. Gabexate mesilate given as a therapy significantly improved the hemodynamic parameters. The study demonstrates an advantageous influence of synthetic antiprotease gabexate mesilate on the course of acute experimental pancreatitis.