Biomedical subjects

M Kilian

Publications and source records attributed to M Kilian.

At least 19 recordsLinked to original sources

PubMed2006

Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic cancer in Syrian Hamsters: inhibition of matrix metalloproteinases in pancreatic cancer.

BACKGROUND: Matrix metalloproteinases (MMP) are proteolytic enzymes which degrade the extracellular matrix and therefore play an important role in metastasis. However, the impact of MMP inhibitors (MMPI) on pancreatic cancer is still unclear. Thus we evaluated the influence of selective MMPI Ro 28-2653 on the incidence of liver metastases and the concentration of MMP-2 and MMP-9 in ductal pancreatic adenocarcinoma in Syrian hamster. MATERIAL AND METHODS: One hundred and thirty male Syrian hamsters were randomised into 8 groups (Gr.1-3: n=15, Gr.4-8: n=17). Pancreatic cancer was induced by weekly subcutaneous injection of 10mg N-nitrosobis-2-oxopropylamin (BOP)/kg body weight (Gr.4-8) while healthy control Gr. 1-3 received 0.5 ml sodium chloride 0.9%. Gr.1 and 4 had free access to a standard diet, Gr. 2, 3 and 5-8 received a diet rich in polyunsaturated fatty acids, which increases liver metastasis in this model. In week 17 oral therapy started: Gr.3 and 6: 60 mg Eudragit/kg body weight/d (vehicle of MMPI), Gr.7 and 8: 40 mg, respectively, 120 mg RO 28-2653/kg body weight/d; Gr.1, 2, 4, 5: no therapy. After 30 weeks all hamsters were sacrificed and histopathologically examined. Additionally concentrations of MMP-2 and MMP-9 were measured in non-metastatic liver and liver metastases. RESULTS: Concentrations of MMP-2 and MMP-9 in liver metastases were decreased by high- and low-dose therapy with MMPI. Furthermore, the incidence of liver metastases was significantly reduced by low-dose therapy with Ro 28-2653. CONCLUSION: Low-dose therapy with Ro 28-2653 decreased liver metastasis due to an inhibition of MMP-2 and MMP-9 concentration in ductal pancreatic cancer.

Animals↗

PubMed2006

Impact of polyunsaturated fatty acids on hepato-pancreatic prostaglandin and leukotriene concentration in ductal pancreatic cancer -- is there a correlation to tumour growth and liver metastasis?

Type and composition of polyunsaturated fatty acids (PUFAs) are suspected to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 PUFAs on tumour growth, liver metastasis and concentration of prostaglandins (PG) and leukotrienes (LT) in experimental ductal pancreatic adenocarcinoma. Ninety male hamsters were randomised into six groups (Gr.) (n=15). While Gr. 1-3 were healthy control groups, Gr. 4-6 weekly received subcutaneous injections of 10mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight for 12 weeks in order to induce ductal pancreatic adenocarcinoma. Between week 1 and 16 all animals were fed with a standard diet with a raw fat content of 2.9%. In week 17 Gr. 1-6 were allocated to three types of diets: Gr. 1: standard high fat (=SHF diet, rich in n-6 PUFAs)/Gr. 2: FISH-OIL (rich in n-3 PUFAs)/Gr. 3: SMOF (=mixture of n-3, n-6 and n-9 PUFAs)/Gr. 4: BOP+SHF/Gr. 5: BOP+SMOF/Gr. 6: BOP+FISH-OIL. After 32 weeks all animals were sacrificed and pancreas as well as liver were analysed histologically. Furthermore pancreatic and hepatic concentrations of prostaglandins (PGF1alpha, PGE(2)) and LT were measured. FISH-OIL decreased number of macroscopically visible pancreatic tumours (Gr. 4-6: 54.5% vs. 45.5% vs. 9.1%, P<0.05) as well as incidence of liver metastasis (Gr. 4-6: 90.9% vs. 72.7% vs. 36.4%, P<0.05). Furthermore concentration of PGF(1)(alpha), PGE(2) and LT were significantly increased in pancreatic carcinoma compared to tumour-free tissue. Moreover levels of PGF(1)(alpha) and PGE(2) were higher in liver metastasis than in extrametastatic hepatic tissue. However, in Gr. 6 (FISH-OIL) intrametastatic concentration of LT was significantly lower than in non-metastatic hepatic tissue as well as in Gr. 4 and Gr. 5. FISH-OIL decreased number of visible pancreatic tumours and incidence of histological proven liver metastasis. This effect might be caused by a decrease of intrametastatic concentration of LT compared to extrametastatic hepatic tissue.

Adenocarcinoma↗

PubMed2006

Two neisseria meningitidis strains with different ability to stimulate toll-like receptor 4 through the MyD88-independent pathway.

Neisseria meningitidis causes acute severe diseases, including sepsis and meningitis, and more benign manifestations such as chronic meningococcemia or colonization of the upper respiratory tract. The inflammatory response, which contributes to the pathogenesis of meningococcal disease, is initiated by pattern recognition receptors, among which Toll-like receptors (TLR)s have been ascribed a particularly important role. We have previously demonstrated that N. meningitidis induce proinflammatory cytokine expression through TLR2 and TLR4. Here we characterize the molecular basis for differential activation of the inflammatory response by two N. meningitidis strains. This difference was due to differential ability to activate signal transduction through TLR4, as HEK293 cells expressing TLR4 produced significantly different levels of interleukin-8 in response to these strains. At the level of signal transduction, the two strains differed substantially in their ability to activate the pathway to nuclear factor kappaB in HEK293-TLR4/MD2 cells at late, but not early, time points. TLR4 activates two signal transduction pathways: one dependent on the adaptor molecule MyD88 and one independent of MyD88, and these pathways induce distinct patterns of gene expression in response to TLR4 ligands. By using macrophages from TLR2-/- mice, we observed that the two strains differed in their ability to activate the TLR4-induced MyD88-independent pathway, but not the MyD88-dependent pathway. This idea was further supported by experiments where either of the two pathways was inhibited and IL-8 secretion was measured. These data therefore provide molecular insight into activation of the inflammatory response by N. meningitidis, which is one of the key events in the pathogenesis of meningococcal disease.

Animals↗

PubMed2005

Influence of different dietary fat intake on liver metastasis and hepatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

OBJECTIVES: Effects of polyunsaturated fatty acids (PUFA) on carcinogenesis are discussed controversially. Thus, tumor growth seems to be influenced by type and composition of fat dietary; however, the pathomechanism is still unknown. Therefore, we investigated the impact of different PUFAs on liver metastasis and hepatic lipid peroxidation in a solid model of ductal pancreatic cancer in Syrian hamsters. METHODS: 90 male hamsters were randomized into 6 groups (n = 15). Accordingly groups 2, 4 and 6 received 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly by subcutaneous injection for 12 weeks in order to induce ductal pancreatic cancer, while groups 1, 3 and 5 were treated with 0.5 ml 0.9% sodium chloride. All hamsters received a standard fat diet (SFD) rich in n-6 PUFA for 16 weeks (2.9% fat). Afterwards, groups 1 and 2 had free access to SFD, while groups 3 and 4 were given a diet enriched with n-3, n-6 and n-9 PUFA (SMOF) and groups 5 and 6 were fed a diet high in n-3 PUFA (FISH-OIL). After 32 weeks all hamsters were sacrificed in order to determine incidence of pancreatic carcinoma and liver metastasis. Furthermore hepatic activities of glutathionperoxidase (GSH-Px) and superoxiddismutase (SOD) as well as levels of lipidperoxidation were analyzed intra- and extrametastatically. RESULTS: The incidence of liver metastasis was decreased in the FISH-OIL tumor group compared to the SFD and SMOF groups. However, GSH-Px activity was not influenced by different diets. Extrametastatic hepatic SOD activity did not differ between all groups, while intrametastatic hepatic SOD activity in the SFD-BOP group was increased. In the FISH-OIL-BOP and the SMOF-BOP group intrametastatic SOD activity was lower than in non-metastatic hepatic tissue. Furthermore levels of hepatic lipid peroxidation were decreased in the tumor groups treated with fish oil and SMOF compared to the SFD group. Comparing intra- and extrametastatic TBARS concentration there was no difference in the SFD-BOP and the SMOF-BOP groups, while in the FISH-OIL-BOP group intrametastatic TBARS concentration was increased. CONCLUSION: Conclusively, fish oil reduced the incidence of liver metastasis in experimental ductal pancreatic cancer. Maybe this effect is caused by an increase of intrametastatic hepatic lipid peroxidation.

Animals↗

PubMed2005

Does enteral nutrition of dietary polyunsaturated fatty acids promote oxidative stress and tumour growth in ductal pancreatic cancer? Experimental trial in Syrian Hamster.

BACKGROUND: Type and composition of dietary fat intake is supposed to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 polyunsaturated fatty acids (PUFA) on oxidative stress (lipidperoxidation) and tumour growth in ductal pancreatic cancer. METHODS: Ninety male hamsters were randomized into 6 groups (gr.) (n=15) and allocated to 3 main dietary categories: gr. 1 and 2 received a standard high fat diet (SHF, rich in n-6 PUFA), while gr. 3 and 4 were fed with a diet containing a mixture of n-3, n-6 and n-9 PUFA (SMOF) and gr. 5 and 6 had free access to a diet rich in n-3 PUFA (FISH-OIL). Gr. 1, 3 and 5 received weekly subcutaneous (s.c.) injections of 10 mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight in order to induce ductal pancreatic adenocarcinoma. Healthy control gr. 2, 4 and 6 were treated with 0.5 ml 0.9% sodium chloride s.c. After 32 weeks all animals were sacrificed. Removed pancreata were weighed and analysed histologically and biochemically. Activities of glutathionperoxidase (GSH-Px), superoxiddismutase (SOD) and levels of lipidperoxidation were measured in samples of pancreatic carcinoma as well as in tumour-free pancreatic tissue. RESULTS: While different diets did not significantly alter the overall incidence of histologically proven pancreatic adenocarcinoma, the number of macroscopically visible tumours was decreased in the FISH-OIL-gr. CONCLUSION: Different diets did not significantly influence the incidence of histologically proven pancreatic adenocarcinoma. However, administration of a diet rich in n-3 PUFA (FISH-OIL) resulted in a decrease of macroscopically visible tumours, thus indicating its beneficial effects in respect to attenuation of tumour growth.

Animals↗

PubMed2005

LapSim virtual reality laparoscopic simulator reflects clinical experience in German surgeons.

BACKGROUND AND AIMS: The aim of this study was to analyze the ability of a training module on a virtual laparoscopic simulator to assess surgical experience in laparoscopy. METHODS: One hundred and fifteen participants at the 120th annual convent of the German surgical society took part in this study. All participants were stratified into two groups, one with laparoscopic experience of less than 50 operations (group 1, n=61) and one with laparoscopic experience of more than 50 laparoscopic operations (group 2, n=54). All subjects completed a laparoscopic training module consisting of five different exercises for navigation, coordination, grasping, cutting and clipping. The time to perform each task was measured, as were the path lengths of the instruments and their respective angles representing the economy of the movements. Results between groups were compared using chi(2) or Mann-Whitney U-test. RESULTS: Group 1 needed more time for completion of the exercises (median 424 s, range 99-1,376 s) than group 2 (median 315 s, range 168-625 s) (P<0.01). Instrument movements were less economic in group 1 with larger angular pathways, e.g. in the cutting exercise (median 352 degrees , range 104-1,628 degrees vs median 204 degrees , range 107-444 degrees , P<0.01), and longer path lengths (each instrument P<0.05). CONCLUSION: As time for completion of exercises, instrument path lengths and angular paths are indicators of clinical experience, it can be concluded that laparoscopic skills acquired in the operating room transfer into virtual reality. A laparoscopic simulator can serve as an instrument for the assessment of experience in laparoscopic surgery.

Chi-Square Distribution↗

PubMed2005

Effects of the antioxidative vitamins A, C and E on liver metastasis and intrametastatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

BACKGROUND/AIMS: Antioxidative vitamins are known to inhibit metastasis. Therefore we evaluated the impact of vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) on liver metastasis in a model of ductal pancreatic adenocarcinoma in hamster. METHODS: One hundred and twenty male Syrian hamsters were randomized into 8 groups (Gr.) (n = 15). Gr. 1-4 were given 0.5 ml normal saline subcutaneously (s.c.) weekly, whereas Gr. 5-8 received 10 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body weight s.c. for 3 months for tumor induction. In the 13th week Gr. 2 and 6 were administered retinol, Gr. 3 and 7 received ascorbic acid and Gr. 4 and 8 were given alpha-tocopherol orally. No treatment was performed in Gr. 1 and 5. After 24 weeks animals were sacrificed, pancreas and liver were histologically determined. Activities of glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD) and concentration of thiobarbituric-acid-reactive substances (TBARS) were analyzed in hepatic tissue. RESULTS: Retinol and alpha-tocopherol decreased the incidence of liver metastases (44.4 vs. 86.7%, p < 0.05). The number and size of liver metastases were significantly reduced by retinol. Activities of GSH-Px and SOD were increased and concentration of TBARS was decreased in NML and LiMe by all vitamins. CONCLUSION: Obviously, antioxidative vitamins prevent oxidative stress in hepatocytes. This may be one mechanism decreasing liver metastasis in pancreatic cancer in the present trial.

Administration, Oral↗

PubMed2005

n-3, n-6, and n-9 polyunsaturated fatty acids--which composition in parenteral nutrition decreases severity of acute hemorrhagic necrotizing pancreatitis in rats?

BACKGROUND AND AIMS: Acute pancreatitis often requires parenteral nutrition. Thus, we analyzed, using a randomized trial, whether different fatty acids in parenteral nutrition influence lipidperoxidation and histopathology in acute pancreatitis in rats. MATERIALS AND METHODS: Seventy-five male Sprague-Dawley rats were randomized into five groups (gr.) (n=15). Gr. 1 underwent a laparotomy followed by saline infusion, gr. 2-5 received intraductal glycodeoxycholic acid (GDOC) followed by intravenous cerulein. Six hours after induction of pancreatitis (IOP), gr. 2 received saline infusion, while gr. 3 was infused with standard lipovenous (rich in [n-6] polyunsaturated fatty acids (PUFA)), gr. 4 received ClinOleic (rich in [n-9] PUFA), while gr. 5 was infused with Omegaven (rich in [n-3] PUFA) for 18 h. After 24 h, all animals were sacrificed and the pancreas was determined histopathologically according to the severity of pancreatitis. Furthermore, pancreatic lipidperoxidation (TBARS) and activity of lipid production protective enzymes superoxide dismutase (SOD) and gluthationperoxidase (GSHPx) were analyzed. RESULTS: Omegaven infusion reduced the severity of histopathologic changes in acute pancreatitis and decreased lipidperoxidation (TBARS) in pancreatic tissue samples. Furthermore, pancreatic activity of SOD was increased. However, standard PUFA and ClinOleic infusion did not influence the severity of pancreatitis and lipidperoxidation. CONCLUSION: Parenteral nutrition high in n-3 PUFA seems to be superior to compositions of n-6 or n-9 PUFA in the treatment of acute hemorrhagic pancreatitis in rats.

Animals↗

PubMed2005

Efficient and fast targeted production of murine models based on ENU mutagenesis.

Mice with targeted genetic alterations are the most effective tools for deciphering organismal gene function. We generated an ENU-based parallel C3HeB/FeJ sperm and DNA archive characterized by a high probability to identify allelic variants of target genes as well as high efficiencies in allele retrieval and model revitalization. Our archive size of over 17,000 samples contains approximately 340,000 independent alleles (20 functional mutations per individual sample). Based on an estimated number of approximately 30,000 mouse genes, the parallel sperm/DNA archive should permit the identification and recovery of ten or more alleles per average target gene which translates to a calculated 99% success rate in the discovery of five allelic variants for any given average gene. The low rate of unrelated ENU-induced passenger mutations has no practical impact on the analysis of the allele-specific phenotype at the G3 generation because of dilution and free segregation of such unrelated passenger mutations. To date 39 mouse models representing 33 different genes have been recovered from our archive using in vitro fertilization techniques. The generation time for a murine model heterozygous for a mutation in a gene of interest is less than 2 months, i.e., three to four times faster compared with current embryonic stem-cell-based technologies. We conclude that ENU-based targeted mutagenesis is a powerful tool for the fast and high-throughput production of murine gene-specific models for biomedical research.

Alleles↗

PubMed2005

Effects of selective COX-2 and 5-LOX inhibition on prostaglandin and leukotriene synthesis in ductal pancreatic cancer in Syrian hamster.

Selective inhibition of eicosanoid synthesis seems to decrease carcinogenesis, however, the effect on liver metastasis in pancreatic cancer is still unknown. Ductal pancreatic adenocarcinoma was chemically induced by weekly injection of N-nitrosobis-2-oxopropylamine (BOP) in Syrian hamster. Animals received selective inhibition of cyclooxygenase-2 (Celebrex) and 5-lipoxygenase (Zyflo). In week 33, hamsters were sacrificed and incidence of pancreatic carcinomas as well as liver metastases were examined. Furthermore, size and number of liver metastases per animal were determined and concentration of PGF1alpha, PGE2 and leukotrienes was measured in hepatic and pancreatic tissue. Combined therapy (Celebrex+Zyflo) significantly decreased incidence, number and size of liver metastases. Furthermore extra- and intrametastatic concentration of PGE2 was reduced by this treatment in hepatic tissue. Single Cox-2-inhibition (Celebrex) decreased intrametastatic hepatic PGF1alpha and PGE2 concentration while PGF1alpha concentration was reduced in non-metastatic liver (nml). Moreover 5-LOX-inhibition (Zyflo) decreased intrametastatic PGE2 concentration as well as PGF1alpha and PGE2 in nml. In pancreatic carcinomas highest LT-concentration was found after combined treatment and this therapy group was the only one revealing a significantly higher amount of LTs in carcinomas compared to tumour-free tissue. Hepatic LT-concentration was significantly lower in the control groups than in nml of the tumour groups. Combination of Cox-2-inhibition and 5-Lox-inhibition might be a suitable adjuvant therapy to prevent liver metastasis in human ductal pancreatic adenocarcinoma.

Animals↗

PubMed2004

Morphology of the rat peritoneum after carbon dioxide and helium pneumoperitoneum: a scanning electron microscopic study.

BACKGROUND: Laparoscopic surgery for patients with cancer has been debated because of the susceptibility that laparoscopic incisions have shown for metastatic tumor growth. Structural damage of the mesothelial layer attributable to the pneumoperitoneum may facilitate intraabdominal tumor cell adhesion and growth. The influence of carbon dioxide (CO(2)) and helium pneumoperitoneum on the morphology of the peritoneum was examined. METHODS: A total of 50 rats received colon carcinoma (DHB/TRb) cells intraperitoneally and CO(2) (n = 25) or helium (n = 25) pneumoperitoneum at 15 mmHg for 15 min. After different periods (2, 12, 24, 48, and 96 h), the rats were killed, and the peritoneum was examined by scanning electron microscopy. Control animals (n = 5) were without pneumoperitoneum. RESULTS: The control animals and most of the rats with pneumoperitoneum showed no peritoneal alterations. In four animals of each group, inflammatory alterations of the peritoneum such as bulging and retraction of mesothelial cells were observed at different time points. Tumor cells adherent to the peritoneum were found in a total of six animals. Peritoneal carcinomatosis, tumor nodules, or infiltration of the peritoneum by tumor cells was not observed. CONCLUSIONS: The study demonstrated that the morphologic integrity of the rat peritoneum is not disturbed when CO(2) or helium is used for insufflation combined with the intraperitoneal injection of carcinoma cells. Pneumoperitoneum therefore probably is not the condition causing peritoneal changes that favor intraperitoneal tumor growth.

Animals↗

PubMed2003

Influence of conjugated and conventional linoleic acid on tumor growth and lipid peroxidation in pancreatic adenocarcinoma in hamster.

Conventional linoleic acid (LA) is regarded as a promotor of carcinogenesis. However, the effect of its conjugated derivative on cancer is still unknown. Therefore we investigated the influence of conventional and conjugated LA on tumor growth and lipid peroxidation in a solid model of pancreatic adenocarcinoma in Syrian hamsters. 60 male hamsters were randomized in 4 groups (Gr.) (n=15). Gr. 1 and 2 received 0.5 ml 0.9% sodium chloride subcutaneously (s.c.) once a week while Gr. 3 and 4 were injected 10 mg N-nitrosobis-2-oxopropylamine (BOP)/kg body weight weekly for 12 weeks to induce pancreatic cancer. Gr. 1 and 3 received a diet containing conventional LA, Gr. 2 and 4 were fed a diet of conjugated LA. After 29 weeks all animals were sacrificed, pancreas was weighed and examined macroscopically and histologically. The level of lipid peroxidation and activities of glutathion peroxidase and superoxide dismutase were determined in tumor-free as well as in pancreatic carcinoma tissue. Different diets did not influence the incidence of pancreatic carcinoma, however, pancreas weight was increased by conjugated LA compared to conventional LA. Furthermore both diets decreased the activity of glutathion peroxidase and increased the level of lipid peroxidation in pancreatic intratumoral tissue. The content of conjugated LA in dietary did not influence pancreatic tumor growth in a solid model of pancreatic adenocarcinoma in Syrian hamsters.

Adenocarcinoma↗

PubMed2003

Effects of taurolidine and octreotide on tumor growth and lipid peroxidation after staging-laparoscopy in ductal pancreatic cancer.

Irrigation with taurolidine after laparoscopy decreases tumor growth in colon carcinoma. In pancreatic cancer subcutaneous therapy with octreotide decreases oxidative stress and carcinogenesis as well. However, it is still unclear, whether irrigation with taurolidine or octreotide after laparoscopic pancreatic biopsy reduces tumor growth in pancreatic cancer as well. In 60 Syrian hamsters ductal pancreatic adenocarcinoma was induced by weekly injection of 10mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. In week 16 laparoscopic pancreatic biopsy by use of carbon dioxide was performed (gr. 1, n = 20) with subsequent laparoscopic irrigation with taurolidine (gr. 2, n = 20) or octreotide (gr. 3, n = 20). In week 25 hamsters were sacrificed. Our results show that macroscopic visible primary tumors were found in only one animal of the taurolidine group (5.9%), compared to 42.1% in the saline and 62.5% in the octreotide group (P<0.05). Carcinomas were smaller after saline (6+/-23 mm(2)) than after octreotide irrigation (70+/-120 mm(2), P<0.05). In conclusion this study showed that laparoscopic irrigation with taurolidine after pancreatic biopsy inhibited tumor growth in ductal pancreatic adenocarcinoma.

Animals↗

PubMed2003

Ciprofloxacin susceptibility of Pseudomonas aeruginosa isolates from keratitis.

AIM: To examine the ciprofloxacin susceptibility of 106 Pseudomonas aeruginosa eye isolates from the United Kingdom, Denmark, India, the United States, and Australia, and to determine the molecular mechanisms of resistance. METHODS: Ciprofloxacin susceptibility was tested by an agar dilution method; genomic DNA corresponding to the quinolone target genes gyrA and parC, and the regulatory genes mexR and nfxB controlling drug efflux systems, was amplified by PCR and sequenced; multilocus enzyme electrophoresis was performed to examine the genetic relation among resistant strains. RESULTS: Three out of 90 keratitis isolates (3.3%), one from the United Kingdom and two from India, exhibited MIC values of 16 mg/l or 32 mg/l. The UK isolate had a mutation in gyrA (Thr83Ile), whereas the two Indian isolates showed mutations in both gyrA (Thr83Ile) and parC (Ser87Leu). The remaining isolates from keratitis, endophthalmitis, contact lens associated red eye (CLARE), and contact lens storage cases showed MIC values below 1 mg/l. Several allelic forms of gyrA and a single variation in the mexR gene product were detected in 10 ciprofloxacin susceptible strains. CONCLUSIONS: The vast majority of eye isolates of P aeruginosa from European countries are fully susceptible to ciprofloxacin and the concentration of ciprofloxacin eye drops used for local treatment (3000 mg/l) exceeds MIC values for strains recorded as resistant. Mutations in more than one target gene were associated with higher MIC values.

Anti-Infective Agents↗

PubMed2002

Effects of taurolidine and octreotide on port site and liver metastasis after laparoscopy in an animal model of pancreatic cancer.

Port site metastasis is a dreadful event following laparoscopy; however, the exact pathomechanism is still unknown. In order to prevent trocar metastasis we determined the effects of intraperitoneal lavage with either taurolidine or octreotide on port site and liver metastasis after laparoscopy in a chemically induced, solid pancreatic adenocarcinoma. Pancreatic adenocarcinoma was induced in 60 Syrian hamsters by weekly injection of 10 mg/kg body weight N-nitrosobis-2-oxopropylamine s.c. for 10 weeks. Six weeks later, a laparoscopic pancreatic biopsy was performed by the use of a pneumoperitoneum with carbon dioxide (12 mm Hg), followed by an abdominal irrigation with 5 ml normal saline (group 1, n = 20), 5 ml 0.5% taurolidine (group 2, n = 20) or 5 ml octreotide (20 mg/ml) (group 3, n = 20). After 8 weeks, all hamsters were sacrificed and histopathologically examined. There was only one macroscopic visible primary tumor in the taurolidine group (5.9%), compared to 42.1% in the saline group and 62.5% in the octreotide group (P < 0.05). The size of carcinomas was smaller in the saline group than after octreotide irrigation (median 6, range 2-25 vs. median 70, range 40-160 mm2, P < 0.05). The number of liver metastases per animal was increased after saline irrigation (median 4, range 2-6), compared to taurolidine (median 2, range 1-3) or octreotide (median 2.5, range 2-4) (P < 0.05). Port site metastases were found in 36.8% after saline, in 37.5% after octreotide and in 0% after taurolidine irrigation (P < 0.05). Thus port site metastasis was effectively prevented by taurolidine irrigation after staging-laparoscopy in pancreatic cancer.

Animals↗

PubMed2002

Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters.

Selective inhibition of eicosanoid synthesis is thought to have effects on carcinogenesis in lung and colon cancer. However, it is still unknown whether pancreatic cancer might also be influenced. Therefore we evaluated the impact of selective cyclooxygenase-2 inhibitor Celebrex and selective 5-lipoxygenase inhibitor Zyflo on liver metastasis in a solid model of pancreatic adenocarcinoma in Syrian hamster. In week 33, the animals were sacrificed and incidence of pancreatic carcinomas and number and size of liver metastases were determined. Activities of antioxidative enzymes (GSHPX/SOD) and concentrations of products of lipidperoxidation were measured in liver metastases and non-metastatic hepatic tissue. The incidence (54.5 vs. 100%), number (3.17 +/- 0.98 vs. 6.75 +/- 0.71) and size (2.67 +/- 1.97 vs. 11.75 +/- 1.98 mm2) of liver metastases were decreased by combined therapy of Zyflo and Celebrex (P < 0.05). Furthermore, activities of GSHPX ([73.77 +/- 5.67]*10(5) vs. [15.49 +/- 4.02]*10(5) U/mg prot.; P < 0.05) and SOD (474.92 +/- 108.8 vs. 127.89 +/- 38.75 U/mg prot.; P < 0.05) were increased, while lipidperoxidation (0.31 +/- 0.08 nmol/mg prot. vs. 1.54 +/- 0.55 nmol/mg prot.; P < 0.05) was decreased by combination therapy, in non-metastatic hepatic tissue. Moreover, combined therapy increased lipidperoxidation in liver metastases (0.47 +/- 0.09 vs. 1.95 +/- 0.12 nmol/mg prot.; P < 0.05). Thus, a combination of Celebrex and Zyflo might be a new concept to decrease tumour growth in liver metastases in advanced pancreatic cancer.

Animals↗

PubMed2002

Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases.

All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases.

Amino Acid Sequence↗

PubMed2002

Intensified microbiological investigations in adult patients admitted to hospital with lower respiratory tract infections.

The objective of this study was to investigate the diagnostic yield of a programme with intensified microbiological investigations in immunocompetent adult patients with lower respiratory tract infections (LRTI). Patients in the study group were included prospectively and consecutively from September 1st 1997 to May 31st 1998 and were compared with a control group from the preceding year. A total of 67 adult patients were included in the study group and they were compared with 122 adult patients in the control group. The study group underwent fibre-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL). Only 7% in the historic control group were discharged with an aetiological diagnosis of their infections; while the diagnostic yield in the study group increased to 51% of patients. In the study group the presence of new infiltrates on chest X-ray increased the detection of a microbiological aetiology from 37% with no infiltrates to 62% with infiltrates and recent antibiotic therapy reduced the detection of a microbiological cause of infection from 61% in 36 patients who had not received antibiotic therapy to 39% in 31 patients who had received recent antibiotic therapy prior to microbiological sampling. Patients in the study group with known aetiology had higher values of inflammatory markers than patients with unknown aetiology. For Streptococcus pneumoniae infection culture and urine antigen detection were complimentary depending on recent antibiotic therapy since seven of eight culture-positive patients had not received antibiotic therapy within 72 h prior to investigation, while all four patients positive for urine antigens from S. pneumoniae had received antibiotic therapy within 72 h of urine sampling. In conclusion intensified microbiologic investigations increase the diagnostic yield from 7% to 51% of patients in the study group with an aetiologic diagnosis. Routine FOB with BAL had no apparent effect on clinical outcome and seems only justified in selected patients with severe LRTI with infiltrates on chest X-ray and signs of severe inflammation where a high diagnostic yield is achieved.

Aged↗