Warm ischemia to liver with subsequent Kupffer cell-dependent pathology is associated with many clinical conditions. Taurine prevents Kupffer cell activation and improves graft survival after ...experimental cold ischemia and liver transplantation. Thus this study was designed to assess its effects after warm hepatic ischemia.
The left liver lobe of female Sprague-Dawley rats (170-210 g) underwent 60 min of warm ischemia. Animals were given either intravenous taurine or Ringer's solution 10 min prior to warm ischemia. Transaminases, histology, in vivo microscopy, intercellular adhesion molecules-1 (ICAM-1) expression, TNF-alpha and tissue hydroperoxide were compared between groups using analysis of variance (ANOVA) or ANOVA on ranks as appropriate.
Taurine significantly decreased transaminases and improved histologic outcome. Phagocytosis of latex beads, serum TNF-alpha levels and tissue hydroperoxide concentrations were also significantly reduced. Stickers in sinusoids and post-sinusoidal venules significantly decreased. In parallel, both leukocyte infiltration and ICAM-1 expression decreased (p < 0.05), while flow velocity of red blood cells as well as sinusoidal perfusion rate were improved (p < 0.05).
This study demonstrates that taurine blunts Kupffer cell-dependent hepatic pathology after warm ischemia in vivo via mechanisms including leukocyte-endothelial interaction, microcirculation disturbances and protection against lipid peroxidation.
Pulmonary vasoconstriction in response to alveolar hypoxia (HPV) is frequently impaired in patients with sepsis or acute respiratory distress syndrome or in animal models of endotoxemia. Pulmonary ...vasodilation due to overproduction of nitric oxide (NO) by NO synthase 2 (NOS2) may be responsible for this impaired HPV after administration of endotoxin (LPS). We investigated the effects of acute nonspecific (N(G)-nitro-L-arginine methyl ester, L-NAME) and NOS2-specific L-N6-(1-iminoethyl)lysine, L-NIL NOS inhibition and congenital deficiency of NOS2 on impaired HPV during endotoxemia. The pulmonary vasoconstrictor response and pulmonary vascular pressure-flow (P-Q) relationship during normoxia and hypoxia were studied in isolated, perfused, and ventilated lungs from LPS-pretreated and untreated wild-type and NOS2-deficient mice with and without L-NAME or L-NIL added to the perfusate. Compared with lungs from untreated mice, lungs from LPS-challenged wild-type mice constricted less in response to hypoxia (69 +/- 17 vs. 3 +/- 7%, respectively, P < 0.001). Perfusion with L-NAME or L-NIL restored this blunted HPV response only in part. In contrast, LPS administration did not impair the vasoconstrictor response to hypoxia in NOS2-deficient mice. Analysis of the pulmonary vascular P-Q relationship suggested that the HPV response may consist of different components that are specifically NOS isoform modulated in untreated and LPS-treated mice. These results demonstrate in a murine model of endotoxemia that NOS2-derived NO production is critical for LPS-mediated development of impaired HPV. Furthermore, impaired HPV during endotoxemia may be at least in part mediated by mechanisms other than simply pulmonary vasodilation by NOS2-derived NO overproduction.
Abstract Background: The mechanism of alcoholic pancreatitis is still unknown. It is of special interest why only about 5% of all alcoholics develop an episode of pancreatitis. We evaluated the role ...of long-term alcohol intake in the pathogenesis of alcoholic pancreatitis in rats. Methods: To evaluate the effect of long-term alcohol intake, rats were fed either a Lieber-DeCarli control diet (CD) or a Lieber-DeCarli alcohol diet (AD) for 6 weeks. Then, rats were infused over 2 h with either Ringer's solution (CO) or ethanol (E). In additional animals, alcoholic pancreatitis was induced by ethanol combined with hyperlipidemia and temporary pancreatic duct obstruction (EFO). Controls received Ringer's solution combined with hyperlipidemia and temporary pancreatic duct obstruction (RFO). Intravital microscopy (pancreatic perfusion and leukocyte adhesion), alcohol concentrations, amylase, lipase, cholesterine and triglyceride levels in plasma, myeloperoxidase activity and histology were evaluated at different time intervals. Results: In those animals which received the Lieber-DeCarli control diet, capillary perfusion was reduced in the E group and further reduced in the EFO group as compared to the controls (CO, RFO; p < 0.01). Leukocyte adhesion was significantly increased in rats receiving E (p < 0.01), and was further increased in the combination group EFO (p < 0.01). EFO induced histologically evident acute pancreatitis. The additional administration of a long-term alcohol diet further increased microcirculatory disturbances and pancreatic injury significantly (EFO-AD > EFO-CD). Conclusions: This study shows that alcoholic pancreatitis is induced by the combination of ethanol and individual cofactors. Chronic alcohol abuse intensifies these changes. Therefore, long-term alcohol intake seems to be a major factor in the pathogenesis of alcoholic pancreatitis.
With the increasing use of the surgical robotic system in the clinical arena, appropriate training programs and assessment systems need to be established for mastery of this new technology. The ...authors aimed to design and evaluate a clinic-like training program for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery.
Four trainees with different surgical levels of experience participated in this study using the da Vinci telemanipulator. Each participant started with an initial evaluation stage composed of standardized visceral and vascular operations (cholecystectomy, gastrotomy, anastomosis of the small intestine, and anastomosis of the aorta) in a porcine model. Then the participants went on to the training stage with the rat model, performing standardized visceral and vascular operations (gastrotomy, anastomosis of the large and small intestines, and anastomosis of the aorta) four times in four rats. The final evaluation stage was again identical to the initial stage. The operative times, the number of complications, and the performance quality of the participants were compared between the two evaluation stages to assess the impact of the training stage on the results.
The operative times in the final evaluation stage were considerably shorter than in the initial evaluation stage and, except for cholecystectomies, all the differences reached statistical significance. Also, significantly fewer complications and improved quality for each operation in the final evaluation stage were documented, as compared with their counterparts in the initial evaluation stage. These improvements were recorded at each level of experience.
The presented experimental small and large animal model is a standardized and reproducible training method for robotic surgery that allows evaluation of the surgical performance while shortening and optimizing the learning-curve.
Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. One of the important diagnostic procedures to recognize reperfusion failure is ...contrast-enhanced computed tomography or magnetic resonance imaging.
To examine the additional effect of contrast media (iomeprol and gadopentetate dimeglumine) on hepatic microcirculation and hepatic cellular damage in the phase of early ischemia/reperfusion injury of the rat liver.
The partial warm ischemia-reperfusion injury model of rat liver was used. Microcirculation and leukocyte-endothelium interaction were measured by intravital microscopy. Hepatic cellular damage was indicated by liver enzyme activity in the sera. The evaluation parameters were measured at baseline and at 30, 60, and 90 min after reperfusion. The contrast media (iomeprol group, n = 6; gadopentetate dimeglumine group, n = 6) or Ringer's solution (control group, n = 8) were applied after 30 min of reperfusion.
No additional injury to the ischemia/reperfusion injury of the liver after intravenous application of radiographic contrast media was found. Some protective effect was even recorded after application of iodinated contrast media.
The use of contrast media during diagnostic procedure of the liver seems to be relatively safe, even in the stage of early reperfusion after liver transplantation.
Hypoxic pulmonary vasoconstriction (HPV) is impaired during inflammatory lung processes such as pneumonia or the acute respiratory distress syndrome. Voltage-gated potassium channels play a central ...role in mediating HPV. The aim of this study was to determine whether 4-aminopyridine (4-AP), a known voltage-gated potassium channel inhibitor, may restore HPV in sepsis.
The effects of 0.01, 0.1, and 1.0 mm 4-AP on HPV responsiveness were assessed in isolated lungs of untreated mice and of mice 18 h after lipopolysaccharide injection (20 mg/kg intraperitoneal Escherichia coli 0111:B4 lipopolysaccharide). HPV was quantified as the increase in perfusion pressure in response to hypoxic ventilation in percent of baseline perfusion pressure. Intrinsic pulmonary vascular resistance (R0) and pulmonary vascular distensibility (alpha) were determined by nonlinear regression analysis of pulmonary vascular pressure-flow curves generated during normoxic and hypoxic ventilation, respectively.
HPV was impaired in lungs isolated from lipopolysaccharide-challenged mice. Addition of 4-AP to the perfusate did not alter HPV responsiveness in untreated mice but dose dependently restored HPV in endotoxemic mice. Analysis of pulmonary vascular pressure-flow curves revealed that 4-AP (1) counteracted the observed lipopolysaccharide-induced changes in alpha and R0 under normoxic conditions and (2) augmented the hypoxia-induced increase in R0 in lungs of endotoxemic mice.
This study demonstrates that lipopolysaccharide-induced pulmonary vascular hyporesponsiveness to hypoxia can be restored by 4-AP in murine endotoxemia and, thus, may be a new therapeutic approach to treat patients with hypoxemia due to impaired HPV.
Low tear production or elevated tear evaporation can lead to severe keratoconjunctivitis sicca. In patients with this disease, the transfer of an autologous submandibular gland into the temporal ...fossa is currently the most common surgical lacrimal gland substituting procedure.
We compared the pre- and postoperative viability of transferred submandibular glands.
Altogether 16 submandibular glands had been transferred in 12 patients. The graft's viability was evaluated before and 0.5-1, 1-6 and 8-12 months after transplantation by dynamic salivary gland scintigraphies after application of 40-50 MBq 99mTc-pertechnetate. Quantitative analysis was performed by calculation and comparison of the glandula submandibularis-to-background-ratio (SBR) and the transplant-to-background-ratio (TBR). The scintigraphic results were correlated with the clinical follow-up.
All grafts remained viable during clinical follow-up. Salivary gland scintigraphy yielded 15 true positive results and 1 false-negative result. Comparison of presurgical SBR and postsurgical TBR showed good correlation with the clinical course. In 10 patients at least one transplant-reduction was necessary due to excessive epiphora occurring averagely 8 months after transplantation.
Our results show that salivary gland scintigraphy very exactly reflects the morphological and biochemical postsurgical changes in a transferred submandibular gland. Thus, it is a reliable tool to exactly and objectively evaluate the viability of the grafts in the postsurgical course.
Although the glottis is amenable to chemotherapy, currently most lesions from stage I laryngeal dysplasia up to carcinoma in situ are excised. This literature review presents selected molecular ...biological aspects especially in relation to dysplasia of the larynx and its therapy, as well as currently preferred biomarkers for chemotherapeutic prevention of laryngeal dysplasia.
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