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Instillation
Kinds of Instillation Terms modified by Instillation Selected AbstractsENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER USING MAGNIFYING ENDOSCOPY WITH A COMBINATION OF NARROW BAND IMAGING AND ACETIC ACID INSTILLATIONDIGESTIVE ENDOSCOPY, Issue 3 2008Kyosuke Tanaka Demarcation of early gastric cancers is sometimes unclear. Enhanced-magnification endoscopy with acetic acid instillation and magnifying endoscopy with a narrow band imaging (NBI) system have been useful for recognition of demarcation of early gastric cancers. We report a patient with early gastric cancer who underwent a successful endoscopic submucosal dissection (ESD) by magnifying endoscopy with the combined use of NBI and acetic acid instillation. A 72-year-old man with early gastric cancer underwent ESD. Demarcation of the lesion was not clear, but magnifying endoscopy using the combination of NBI and acetic acid clearly revealed the demarcation. ESD was carried out after spots were marked circumferentially. We identified the positional relation between the demarcation and all markings. Resection of the lesion was on the outside of the markings. Histopathologically, the lesion was diagnosed as a well-differentiated adenocarcinoma limited to the mucosa. The margins were carcinoma free. Magnifying endoscopy combining the use of NBI with acetic acid instillation is simple and helpful for identifying the demarcation of early gastric cancer. This method may be useful in increasing the rate of complete resection by ESD for early gastric cancer. [source] Fas ligand-induced murine pulmonary inflammation is reduced by a stable decoy receptor 3 analogueIMMUNOLOGY, Issue 2 2003Mark A. Wortinger Summary Fas ligand (FasL)-induced lung inflammation has recently been suggested to play an important role in the pathogenesis of acute respiratory disease syndrome (ARDS). In order to further explore this connection, we established a FasL-induced murine model of pulmonary inflammation. Instillation of recombinant FasL (rFasL) into the lung induced neutrophil infiltration and increased pulmonary permeability, as evidenced by increased total protein in the airspace; both occur in patients with ARDS. These effects were accompanied with a rapid induction of proinflammatory mediators: cytokine granulocyte,macrophage colony-stimulating factor (GM-CSF) and the chemokines macrophage inflammatory protein-2 (MIP-2) and KC. Pretreatment with a FasL antagonist, a decoy receptor 3 analogue (DcR3 analogue), reduced neutrophil infiltration into the airspace and resulted in a highly significant reduction in the levels of GM-CSF, MIP-2 and KC in bronchoalveolar lavage (BAL) fluid. We postulate that rFasL may be responsible for induction of proinflammatory chemokines and cytokines in the lung, which in turn attract neutrophil infiltration into the airspace. This proinflammatory process and the associated pulmonary permeability may, in part, explain the association of FasL with severe pulmonary inflammation, such as ARDS, and shed new light on FasL and its role in lung injury. [source] Experimental Efficacy of Pericardial Instillation of Anti-inflammatory Agents during Percutaneous Epicardial Catheter Ablation to Prevent Postprocedure PericarditisJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2007ANDRE D'AVILA M.D. Introduction: Pericarditis is a potential complication of catheter-based percutaneous epicardial mapping and ablation. This study evaluates the efficacy and safety of intrapericardial instillation of anti-inflammatory agents after pericardial mapping and ablation in a porcine model of postprocedural pericarditis. Methods and Results: Twenty-five healthy swine underwent epicardial mapping and ablation after transthoracic subxyphoid puncture. After 60 minutes of continuous catheter manipulation in the pericardial space, radiofrequency energy was delivered in a linear fashion to the epicardial surfaces of both atria. The animals were randomly divided to receive the anti-inflammatory agents, Hyaluronic Acid and Triamcinolone, or control. Fourteen days after ablation, the hearts were excised and the degree of pericardial reaction/adhesions scored. The severity was uniformly graded 4 (intense) in all control animals and was characterized by intense adhesion between the parietal and the visceral pericardium obscuring tissue planes and epicardial anatomy. Hyaluronic Acid provided a mild benefit (score 3.0 ± 0.9), but 2 mg/kg of Triamcinolone significantly attenuated the inflammatory effect (all animals uniformly scored 1.0). Conclusion: In a porcine model of ablation-related pericarditis, intrapericardial instillation of 2 mg/kg of intermediate-acting corticosteroids effectively prevents post-procedure inflammatory adhesion formation. [source] The role of capsaicin-sensitive afferents in autonomic dysreflexia in patients with spinal cord injuryBJU INTERNATIONAL, Issue 7 2003Y. Igawa OBJECTIVES To determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). PATIENTS AND METHODS Seven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyper-reflexia (DH) were enrolled. Under general anaesthesia, capsaicin solution (100 mL of 2 mmol/L in 10% ethanol) was instilled in the bladder and retained for 30 min. The patients were assessed by medium-fill cystometry (CMG) just before and 50 min after the capsaicin treatment. Intra-arterial blood pressure (BP) and heart rate were monitored continuously throughout the procedure; 10% ethanol was instilled before capsaicin treatment in four patients as a control. Serum catecholamines were measured during bladder filling and capsaicin treatment, and the blood ethanol concentration also measured after instillation in all patients. The CMG with concomitant monitoring of BP and heart rate was repeated 1 week, 1, 3, 6, 12 and 24 months after instillation. In two patients the instillations were repeated 5 and 12 months after the first because of recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH2O detrusor pressure (Cdp40) and a systolic BP of> 140 mmHg or diastolic BP of> 90 mmHg (CHT). RESULTS There was an increase in BP and a decrease in heart rate in all patients during bladder filling before capsaicin treatment. Instillation of capsaicin produced a significant increase in both systolic and diastolic BP and a significant decrease in heart rate. The maximum cardiovascular effects were at 5,10 min after instillation and gradually returned to baseline within 40 min. The vehicle had negligible effects on either BP or heart rate. After capsaicin treatment, the responses of BP and heart rate to bladder distension were significantly reduced. Both serum catecholamine values and the blood ethanol concentration remained within normal limits. The mean (range) follow-up after the first treatment was 15 (6,30) months. One month after treatment all seven patients became continent and their episodes of AD became negligible and well tolerable between catheterizations (for 3,4 h); the effects lasted for , 3 months in all. MCC was significantly increased at 4 weeks and 3 months, and UICmax significantly decreased at 4 weeks after treatment. Both mean Cdp40 and CHT increased 1 week, 1 and 3 months after treatment. Two patients received a second instillation, and have been continent with no symptomatic AD for 6 and 24 months. The remaining five patients have been continent with no symptomatic AD for 6,12 months. CONCLUSION These results indicate that intravesical capsaicin, but not the vehicle, acutely triggers AD in patients with SCI, suggesting involvement of bladder capsaicin- sensitive afferents in AD in these patients. The results also suggest that intravesical capsaicin may be a promising therapy for both AD and DH in such patients. Further long-term follow-up studies are needed to evaluate the duration of its effect. [source] Factors regulating renal angiotensin-converting enzyme activity in the ratACTA PHYSIOLOGICA, Issue 1 2000Changes in angiotensin-converting enzyme (ACE) activity appear to be important in mediating the natriuresis which ensues after administration of an oral or gastric sodium load. In this study, we sought to determine the time course of the changes in ACE activity in the kidney which occur after sodium ingestion. In addition, we sought to investigate mechanisms which might underlie these changes. Angiotensin-converting enzyme activity was measured by generation of histidyl-leucine in homogenates of kidneys harvested at varying time-points after gastric sodium administration. The effects of intravenous sodium loading, solution osmolality and of changes in renal nerve activity were also investigated. Intragastric instillation of both the sodium-containing solution and its iso-osmotic urea control solution resulted in significant increases in renal ACE activity (NaCl: P < 0.0005; Urea: P < 0.01). The increase in renal ACE activity after gastric sodium loading was more prolonged than after the urea control (P < 0.025, NaCl vs. urea at 90 min). This prolonged increase in renal ACE activity appeared to reflect a response to absorbed sodium as intravenous sodium administration caused a significant increase in renal ACE activity at 90 min (P < 0.0005). In contrast to these stimuli which increased renal ACE activity, renal denervation caused a significant decrease in ACE activity in the kidney (P < 0.05). We conclude that gastric sodium loading increases renal ACE activity. This effect appears to be due initially to a response to an increase in gastric lumenal osmolality and later to absorbed sodium. These changes in renal ACE activity are not mediated by a decrease in renal nerve activity. [source] ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER USING MAGNIFYING ENDOSCOPY WITH A COMBINATION OF NARROW BAND IMAGING AND ACETIC ACID INSTILLATIONDIGESTIVE ENDOSCOPY, Issue 3 2008Kyosuke Tanaka Demarcation of early gastric cancers is sometimes unclear. Enhanced-magnification endoscopy with acetic acid instillation and magnifying endoscopy with a narrow band imaging (NBI) system have been useful for recognition of demarcation of early gastric cancers. We report a patient with early gastric cancer who underwent a successful endoscopic submucosal dissection (ESD) by magnifying endoscopy with the combined use of NBI and acetic acid instillation. A 72-year-old man with early gastric cancer underwent ESD. Demarcation of the lesion was not clear, but magnifying endoscopy using the combination of NBI and acetic acid clearly revealed the demarcation. ESD was carried out after spots were marked circumferentially. We identified the positional relation between the demarcation and all markings. Resection of the lesion was on the outside of the markings. Histopathologically, the lesion was diagnosed as a well-differentiated adenocarcinoma limited to the mucosa. The margins were carcinoma free. Magnifying endoscopy combining the use of NBI with acetic acid instillation is simple and helpful for identifying the demarcation of early gastric cancer. This method may be useful in increasing the rate of complete resection by ESD for early gastric cancer. [source] Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studiesDRUG DEVELOPMENT RESEARCH, Issue 6 2009A.S. Manjappa Abstract Most ocular diseases are treated with topical eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of the nonsteroidal anti-inflammatory drug (NSAID), ketorolac tromethamine, based on the concept of pH-triggered in situ gelation. Polyacrylic acid (Carbopol® 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel E15LV), which acted as a viscosity enhancer. The prepared formulations were characterized for clarity, pH, drug content, rheology, and in vivo drug release. Clarity, pH, and drug content of the developed formulations were found to be satisfactory. The developed formulation showed pseudo-plastic rheology. The formulation with benzalkonium chloride and edetate disodium improved the rate of corneal absorption but not the extent. The developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain drug release. Also importantly is the ease of instillation afforded and decreased frequency of instillation resulting in better patient acceptance. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] A Sheep Model for the Study of Focal Epilepsy with Concurrent Intracranial EEG and Functional MRIEPILEPSIA, Issue 8 2002Helen I. Opdam Summary: ,Purpose: We describe a sheep model of penicillin-induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI). Methods: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000,10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level,dependent (BOLD) weighted signal intensity at different times during the evolution of seizures. Results: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 ± 11.2 s and 17.3 ± 12.1 min after penicillin administration, respectively. An average of 13 ± 4.8 seizures were seen per animal, each lasting 27.3 ± 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala. Conclusions: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico,subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain. [source] Pulmonary response to airway instillation of autologous blood in horsesEQUINE VETERINARY JOURNAL, Issue 4 2007F. J. DERKSEN Summary Reasons for performing study: Exercise-induced pulmonary haemorrhage (EIPH) occurs in the majority of horses performing strenuous exercise. Associated pulmonary lesions include alveolar and airway wall fibrosis, which may enhance the severity of EIPH. Further work is required to understand the pulmonary response to blood in the equine airways. Objectives: To confirm that a single instillation of autologous blood into horse airways is associated with alveolar wall fibrosis, and to determine if blood in the airways is also associated with peribronchiolar fibrosis. Methods: Paired regions of each lung were inoculated with blood or saline at 14 and 7 days, and 48, 24 and 6 h before euthanasia. Resulting lesions were described histologically and alveolar and airway wall collagen was quantified. Results: The main lesion observed on histology was hypertrophy and hyperplasia of type II pneumocytes at 7 days after blood instillation. This lesion was no longer present at 14 days. There were no significant effects of lung region, treatment (saline or autologous blood instillation), nor significant treatment-time interactions in the amount of collagen in the interstitium or in the peribronchial regions. Conclusion: A single instillation of autologous blood in lung regions is not associated with pulmonary fibrosis. Potential relevance: Pulmonary fibrosis and lung remodelling, characteristic of EIPH, are important because these lesions may enhance the severity of bleeding during exercise. A single instillation of autologous blood in the airspaces of the lung is not associated with pulmonary fibrosis. Therefore the pulmonary fibrosis described in EIPH must have other causes, such as repetitive bleeds, or the presence of blood in the pulmonary interstitium in addition to the airspaces. Prevention of pulmonary fibrosis through therapeutic intervention requires a better understanding of these mechanisms. [source] The effects of local anaesthetic solution in the navicular bursa of horses with lameness caused by distal interphalangeal joint painEQUINE VETERINARY JOURNAL, Issue 5 2003JOHN SCHUMACHER Summary Reasons for performing study: Analgesia of the palmar digital (PD) nerves has been demonstrated to cause analgesia of the distal interphalangeal (DIP) joint as well as the sole. Because the PD nerves lie in close proximity to the navicular bursa, we suspected that that analgesia of the navicular bursa would anaesthetise the PD nerves, which would result in analgesia of the DIP joint. Objectives: To determine the response of horses with pain in the DIP joint to instillation of local anaesthetic solution into the navicular bursa. Methods: Lameness was induced in 6 horses by creating painful synovitis in the DIP joint of one forefoot by administering endotoxin into the joint. Horses were videorecorded while trotting, before and after induction of lameness, at three 10 min intervals after instilling 3.5 ml local anaesthetic solution into the navicular bursa and, finally, after instilling 6 ml solution into the DIP joint. Lameness scores were assigned by grading the videorecorded gaits subjectively. Results: At the 10 and 20 min observations, median lameness scores were not significantly different from those before administration of local anaesthetic solution into the navicular bursa (P,0.05), although lameness scores of 3 of 6 horses improved during this period, and the 20 min observation scores tended toward significance (P = 0.07). At the 30 min observation, and after analgesia of the DIP joint, median lameness scores were significantly improved (P,0.05). Conclusions: These results indicate that pain arising from the DIP joint can probably be excluded as a cause of lameness, when lameness is attenuated within 10 mins by analgesia of the navicular bursa. Potential relevance: Pain arising from the DIP joint cannot be excluded as a cause of lameness when lameness is attenuated after 20 mins after analgesia of the navicular bursa. [source] Airway inflammation: chemokine-induced neutrophilia and the class,I phosphoinositide 3-kinasesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2005Matthew Abstract Class,I phosphoinositide 3-kinases (PI3K) are known to play a significant role in neutrophil chemotaxis. However, the relative contributions of different PI3K isoforms, and how these impact on lung inflammation, have not been addressed. In vitro studies using wild-type and PI3K, knockout neutrophils demonstrated the major role of the ,,isoform in chemotactic but not chemokinetic events. This was confirmed by a model of direct chemokine instillation into the airways in vivo. Within all studies, a low yet significant degree of neutrophil movement in the absence of PI3K, could be observed. No role for the ,,isoform was demonstrated both in vitro and in vivo using PI3K, kinase-dead knock-in mice. Moreover, further studies using the broad-spectrum PI3K inhibitors wortmannin or LY294002 showed no other class,I PI3K isoforms to be involved in these chemotactic processes. Here, we identify a contributory PI3K-independent mechanism of neutrophil movement, yet demonstrate PI3K, as the pivotal mediator through which the majority of neutrophils migrate into the lung in response to chemokines. These data resolve the complexities of chemokine-induced neutrophilia and PI3K signaling and define the ,,isoform as a promising target for new therapeutics to treat airway inflammatory diseases. [source] Abstract no.: 2 The influence of clozapine on tone of isolated bovine retinal arteriesFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2005Koen Boussery Aims:, It has been suggested that the atypical antipsychotic drug clozapine might be helpful in the development of new antiglaucoma agents, since it combines lowering of the intra-ocular pressure after topical instillation with vasodilation. However, the vasoactive influence of clozapine on ocular blood vessels has never been analysed. Therefore, this study aimed to evaluate whether clozapine has direct vasodilatory effects in isolated bovine retinal arteries (BRA) and to characterise pharmacologically the mechanisms involved. Methods:, Retinal arteries were isolated from bovine eyes and mounted in a wire-myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of clozapine (1 nM to 10 ,M) to the organ bath. Results:, Clozapine elicited a concentration-dependent relaxation of the BRA. Removal of the endothelium of the BRA, inhibition of nitric oxide synthase with N, -nitro-L-arginine and inhibition of soluble guanylyl cyclase with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) significantly attenuated the clozapine-response, whereas cyclo-oxygenase inhibition with indomethacin had no influence. The Ca2+ channel activator Bay k8644, the nonselective 5-hydroxytryptamine receptor antagonist methiothepin and the adenosine receptor antagonist 8-(p-sulfophenyl) theophylline also failed in affecting the clozapine-induced relaxations. Conclusion:, Clozapine clearly relaxes bovine retinal arteries in a direct way. Endothelium-derived NO is involved in this response. However, prostanoids, calcium entry blockade, 5-HT7 receptor stimulation and adenosine receptor stimulation all seem to be not involved. [source] Activator protein-1 signalling pathway and apoptosis are modulated by poly(ADP-ribose) polymerase-1 in experimental colitisIMMUNOLOGY, Issue 4 2004Basilia Zingarelli Summary Poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA injury in the nucleus of eukaryotic cells and has been implicated in intestinal barrier dysfunction during inflammatory bowel diseases. In this study we investigated whether PARP-1 may regulate the inflammatory response of experimental colitis at the level of signal transduction mechanisms. Mice genetically deficient of PARP-1 (PARP-1,/,) and wild-type littermates were subjected to rectal instillation of trinitrobenzene sulphonic acid (TNBS). Signs of inflammation were monitored for 14 days. In wild-type mice, TNBS treatment resulted in colonic ulceration and marked apoptosis, which was associated with decreased colon content of the antiapoptotic protein Bcl-2, whereas the proapoptotic Bax was unchanged. Elevated levels of plasma nitrate/nitrite, metabolites of nitric oxide (NO), were also found. These inflammatory events were associated with activation of c-Jun-NH2 terminal kinase (JNK), phosphorylation of c-Jun and activation of the nuclear transcription factor activator protein-1 (AP-1) in the colon. In contrast, PARP-1,/, mice exhibited a significant reduction of colon damage and apoptosis, which was associated with increased colonic expression of Bcl-2 and lower levels of plasma nitrate/nitrite when compared to wild-type mice. Amelioration of colon damage was associated with a significant reduction of the activation of JNK and reduction of the DNA binding of AP-1. The data indicate that PARP-1 exerts a pathological role in colitis possibly by regulating the early stress-related transcriptional response through a positive modulation of the AP-1 and JNK pathways. [source] Role of NK1.1+ and AsGm-1+ cells in oral immunoregulation of experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 2 2003Shivti Trop Abstract NK1.1 and AsGm-1 expressing cells play a role in immunomodulation. Our purpose was to determine the role of NK1.1+ and AsGm-1+ expressing cells in the inflammatory/tolerance paradigm in experimental colitis. Oral tolerance towards colitis-extracted proteins had previously been shown to alleviate experimental colitis. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Oral tolerance was induced via five oral doses of proteins extracted from TNBS-colitis colonic wall. Clinical, macroscopic, and microscopic scores were used for colitis assessment. To evaluate the putative role of AsGm-1 in tolerance induction, depletion of AsGm-1 expressing cells was performed. To evaluate the mechanism of tolerance induction, liver-associated NKT lymphocytes were harvested 14 days following tolerance induction, and cultured with concanavalin A (con A) and colitis-extracted proteins. T cell subsets were measured by flow cytometry. Cytokine expression was measured by intracellular staining and enzyme-linked immunosorbent assay (ELISA). Orally tolerized mice exhibited significant alleviation of the clinical, macroscopic, and microscopic parameters of colitis, with increased CD4+IL4+/CD4+IFN,+ lymphocyte ratio, increased IL-4, and decreased IFN, and IL-12 serum levels. In contrast, orally fed mice that were AsGm-1 depleted showed evidence of severe colitis. These mice exhibited significant decreased CD4+IL4+/CD4+IFN,+ ratios, and an increase in IFN, and IL-12, with decreased IL-4 levels. NKT cells harvested from tolerized mice secreted high levels of antiinflammatory cytokines. In contrast, in nontolerized mice, NKT cells mainly secreted proinflammatory cytokines. In a tolerized environment, both NK1.1 and AsGm-1 expressing cells are essential for disease alleviation. In contrast, in a nontolerized environment, AsGm-1 expressing cells support an antiinflammatory immune paradigm, while NKT lymphocytes support a proinflammatory shift. [source] Medical thoracoscopy in an Australian regional hospitalINTERNAL MEDICINE JOURNAL, Issue 4 2007G Simpson Abstract Medical thoracoscopy is not widely available in Australia. A medical thoracoscopy service has been set up in a regional hospital using no specialized equipment and at minimal cost. Of the first 100 procedures carried out, 89 were for investigation of pleural effusion, 6 for pneumothorax and 6 for empyema. Of the 89 pleural effusions, 73 were diagnosed as malignant (43 carcinoma, 24 mesothelioma, 3 lymphoma, 2 melanoma and 1 sarcoma). The sensitivity for a malignant diagnosis was 94.5%, with 100% specificity. Four patients had unsuspected tuberculous effusions. Pleurodesis was carried out with instillation of dry sterile talc in 67 cases. In 92.5% of these, no further drainage procedure was needed. There was one fatality caused by pre-existing sepsis in a debilitated patient with disseminated carcinoma. Medical thoracoscopy is a simple, safe and cost-effective technique for diagnosing and treating pleural effusions and provides a useful service in the setting of a regional hospital. [source] Effect of IL-2-Bax, a novel interleukin-2-receptor-targeted chimeric protein, on bleomycin lung injury,INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2005Michael J. Segel Summary The role of lymphocytes in the pathogenesis of lung fibrosis is not clear, but the weight of the evidence supports a pro-fibrotic effect for lymphocytes. The high-affinity interleukin-2 receptor (haIL-2R) is expressed on activated, but not quiescent, T lymphocytes. This selective expression of haIL-2R provides the basis for therapeutic strategies that target IL-2R-expressing cells. We hypothesized that elimination of activated lymphocytes by IL-2R-targeted chimeric proteins might ameliorate lung fibrosis. We investigated the effects of IL-2-Bax, a novel apoptosis-inducing IL-2R-targeted chimeric protein, on bleomycin-induced lung injury in mice. Treatment groups included (i) a single intratracheal instillation of bleomycin and twice-daily intraperitoneal injections of IL-2-Bax; (ii) intratracheal bleomycin and intraperitoneal IL-2-PE664Glu, an older-generation chimeric protein; (iii) intratracheal bleomycin/intraperitoneal PBS; (iv) intratracheal saline/intraperitoneal PBS. Lung injury was evaluated 14 days after intratracheal instillation by cell count in bronchoalveolar lavage (BAL) fluid, semi-quantitative and quantitative histomorphological measurements and by biochemical analysis of lung hydroxyproline. Bleomycin induced a BAL lymphocytosis that was significantly attenuated by IL-2-Bax and IL-2-PE664Glu. However, morphometric parameters and lung hydroxyproline were unaffected by the chimeric proteins. These results show that IL-2-Bax reduces the lymphocytic infiltration of the lungs in response to bleomycin, but this effect is not accompanied by a decrease in lung fibrosis. [source] Time course of bleomycin-induced lung fibrosisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2002G. Izbicki Summary. Intratracheal instillation (IT) of bleomycin is a widely used experimental model for lung fibrosis. In this study we describe the time-course of bleomycin-induced lung fibrosis in mice using computer-assisted morphometry. C57Bl/6J mice were treated with a single IT dose of bleomycin or control saline. Animals were killed 3, 6, 14 and 21 days post-IT. Lung injury was evaluated by analysis of bronchoalveolar lavage (BAL) fluid, hydroxyproline concentration in the lung, routine light microscopic examination resulting in a semiquantitative morphological index (SMI) of lung injury, and quantitative morphological measurements (fibrosis fraction and alveolar wall area fraction) aided by optimas image analysis software. Changes in BAL fluid attributed to bleomycin treatment include increased total cell count (days 14 and 21), and increased percentage of neutrophils (days 3 and 6) followed by a sustained increase in lymphocytes (days 6, 14 and 21). Hydroxyproline levels increased in bleomycin-treated mice on days 14 and 21. Median SMI grades were significantly elevated on days 3, 14 and 21. Computer-assisted morphometry demonstrated a 3-fold increase in fibrosis fraction and a 1.3-fold increase in wall area fraction in bleomycin-treated mice on day 14, with no further increase on day 21. These data also demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days after IT instillation of bleomycin, based on the observation that at 14 days the animals developed extensive fibrosis, but had less variability in the fibrotic response and lower mortality than later at 21 days. Computer-assisted morphometry provides objective and quantitative measurements that are a useful tool for the evaluation of bleomycin-induced lung injury. [source] Intravesical acetic acid instillation to detect malignant changes in the bladder mucosa: Preliminary reportINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2009Keiji Iizuka md No abstract is available for this article. [source] Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapyINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2007Yasuyo Shintani Aim: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. Methods: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte,macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-,, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1,, IL-8, interferon (IFN)-,, and IL-12. Results: After the BCG therapy, various cytokines, such as GM-CSF, TNF-,, G-CSF, IL-1,, IL-8, IFN-,, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-, 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-, or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-, level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. Conclusions: We suggested that the urinary levels of TNF-, might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence. [source] Granulomatous balanoposthitis after intravesical Bacillus-Calmette-Guerin instillation therapyINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2006HATTORI YUSUKE Abstract, We report a rare case of granulomatous balanoposthitis after intravesical Bacillus-Calmette-Guerin (BCG) instillation therapy in a 58-year-old man, which followed transurethral resection (TUR) for recurrent bladder cancer, when his anterior urethra was slightly narrow and his foreskin was with phimosis. Intravesical BCG instillation therapy was started for prophylaxis of recurrent bladder cancer after TUR. Multiple painless firm papules on glans penis, edema in the foreskin and low-grade fever appeared after the seventh instillation, for which the single antituberculous agent isoniazid (300 mg/day) was administered. Biopsy of the papules on glans penis and foreskin revealed granulomatous balanoposthitis. Low-grade fever normalized and the papules disappeared within 1 week. The patient continued chemotherapy with isoniazid for the next 12 months. There was no recurrence of bladder cancer or balanoposthitis for 15 months and to date. [source] Transient anuria requiring nephrostomy after intravesical bacillus Calmette-Guérin instillations for superficial bladder cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2006TOMOYUKI KANEKO Abstract, A 76-year-old man received intravesical bacillus Calmette-Guérin (BCG) instillations for recurrent superficial bladder cancer. He had undergone right nephroureterectomy for right renal pelvic cancer 9 months previously. He presented with anuria and left hydronephrosis after the fourth instillation, with serum creatinine increasing up to 15.7 mg/dL. Percutaneous nephrostomy was indwelled, and antegrade pyelography showed left vesicoureteral obstruction. There was no sign of recurrent bladder cancer or ureteral cancer. He started spontaneous voiding on day 4 and the nephrostomy was removed on day 8. Most of the side-effects of intravesical BCG therapy are minor, and major adverse reactions are rare. Life-threatening ureteral obstruction would be a rare complication of BCG immunotherapy. Although BCG intravesical instillation after nephroureterectomy is a common practice, special care should be taken of renal function in patients with unilateral kidney during BCG therapy. [source] Sufficient prophylactic efficacy with minor adverse effects by intravesical instillation of low-dose bacillus Calmette-Guérin for superficial bladder cancer recurrenceINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2003AKIRA IRIE Abstract Background: Intravesical instillation of bacillus Calmette-Guérin (BCG) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence. Adverse effects of BCG are major obstacles, but the reduction of BCG dose could minimize these effects. The efficacy and adverse effects of half-dose (40 mg) BCG, Tokyo 172 strain, were prospectively evaluated. Methods: A total of 93 patients with superficial bladder cancer (pTa or pT1) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection. BCG was administered weekly for 6 weeks postoperatively. Eighty patients observed longer than 12 months after BCG therapy (41, 40 mg group; 39, 80 mg group) were analyzed. Results: BCG therapy course was completed in 71 patients. Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group. There was no significant difference in tumor recurrence rate between the two groups (P = 0.547). BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects. The morbidity of BCG-related toxicity was significantly higher in the 80 mg group. Conclusion: Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the standard dose. Thus, half-dose of this strain might be suitable, at least for initial BCG therapy, for the prophylaxis of bladder cancer recurrence. Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients. [source] Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside for prevention of recurrent bladder tumors following surgery for upper urinary tract tumors: A prospective randomized studyINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2001Naotaka Sakamoto Abstract Background: A recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract is not rarely observed. A prospective randomized study was conducted to examine the significance of prophylactic intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara-C) to prevent recurrent bladder tumors after surgery for superficial transitional cell carcinoma of the upper urinary tract. Methods: The patients were randomized into an instillation group, who received postoperative intravesical instillation of MMC (20 mg) and Ara-C (200 mg) 28 times over a period of 2 years, and a non-instillation group. The non-recurrence rate was then compared between the groups. Results: Of the 27 patients registered, 25 patients (13 with instillation and 12 without instillation) were able to be evaluated, with a median follow-up period of 45 months. The non-recurrence rate of bladder tumors in the instillation group was higher than that in the non-instillation group. Although the difference was not statistically significant, the P -value (P = 0.079) demonstrated a strong trend. When any possible bias was allowed for a multivariate analysis, the difference was almost significant (P = 0.0567). No patients withdrew from this study due to any side-effects. Conclusion: The postoperative instillation of MMC and Ara-C may be a useful approach for reducing the recurrence of bladder tumors after surgery for upper urinary tract tumors. [source] Late sensory function after intraoperative capsaicin wound instillationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2010E. K. AASVANG Background: Intense capsaicin-induced C-fiber stimulation results in reversible lysis of the nerve soma, thereby making capsaicin wound instillation of potential interest for the treatment of post-operative pain. Clinical histological and short-term sensory studies suggest that the C-fiber function is partly re-established after skin injection of capsaicin. However, no study has evaluated the long-term effects of wound instillation of purified capsaicin on sensory functions. Methods: Patients included in a double-blind placebo-controlled randomized study of the analgesic effect of capsaicin after groin hernia repair were examined by quantitative sensory testing before, 1 week and 2 years post-operatively. The primary endpoint was occurrence of hyperalgesia/allodynia. The secondary endpoints were acute and late sensory changes between the two patient groups. Patients were blinded to the allocated treatment. Results: Twenty (100%) capsaicin and 16 (76%) placebo-treated patients were seen at the year follow-up. Hyperalgesia was seen in five capsaicin- vs. one placebo-treated patient (P=0.2). The mechanical detection threshold was significantly increased on the operated side in the capsaicin vs. placebo group at the 1-week follow-up (P<0.05), but was not different at the year follow-up (P=0.3). There were no other significant differences in sensory function on the operated side between groups at the pre-operative, 1-week or year post-operative follow-up (P>0.05). The sensory function on the contralateral side was comparable between groups throughout the study (P>0.1). Conclusion: This small-volume study calls for further long-term safety studies of wound capsaicin instillation. [source] A comparative study of the preventative effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitisJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2007L. Peran Abstract Aims:, The intestinal anti-inflammatory effects of three probiotics with immunomodulatory properties, Lactobacillus casei, Lactobacillus acidophilus and Bifidobacterium lactis, were evaluated and compared in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Methods and Results:, Colitis was induced in rats by intracolonic administration of 10 mg of TNBS dissolved in 0·25 ml of 50% ethanol. Each probiotic was administered orally (5 × 108 CFU suspended in 0·5 ml of skimmed milk) for 3 weeks, starting 2 weeks before the administration of TNBS. Colonic damage was evaluated histologically and biochemically 1 week after TNBS instillation. The results obtained revealed that all probiotics assayed showed intestinal anti-inflammatory effects, macroscopically evidenced by a significant reduction in the colonic weight/length ratio. Only B. lactis showed a lower incidence of diarrhoea in comparison with untreated rats. Biochemically, all probiotics restored colonic glutathione levels, depleted as a consequence of the oxidative stress of the inflammatory process. Bifidobacterium lactis treatment reduced colonic tumour necrosis factor (TNF)-, production, and inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression; L. acidophilus administration reduced colonic leukotriene B4 production and iNOS expression and L. casei intake was associated with a decrease in colonic COX-2 expression. Conclusion:, The three probiotics assayed have shown intestinal anti-inflammatory activity in the TNBS model of rat colitis, although each probiotic shows its own anti-inflammatory profile. Significance and Impact of the Study:, These probiotics could be considered as potential adjuvants in the treatment of inflammatory bowel disease, although more studies are required in order to demonstrate their efficacy in humans. [source] Comparison of the effects of erdosteine and N-acetylcysteine on apoptosis regulation in endotoxin-induced acute lung injuryJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2006Rezan Demiralay Abstract This study was carried out to investigate comparatively the frequency of apoptosis in lung epithelial cells after intratracheal instillation of endotoxin [lipopolysaccharide (LPS)] in rats and the role of tumor necrosis factor alpha (TNF- ,) on apoptosis, and the effects of erdosteine and N-acetylcysteine on the regulation of apoptosis. Female Wistar rats were given oral erdosteine (10,500 mg kg,1) or N-acetylcysteine (10,500 mg kg,1) once a day for 3 consecutive days. Then the rats were intratracheally instilled with LPS (5 mg kg,1) to induce acute lung injury. The rats were killed at 24 h after LPS administration. Lung tissue samples were stained with hematoxylin-eosin for histopathological assessments. The apoptosis level in the lung bronchial and bronchiolar epithelium was determined using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Cytoplasmic TNF- , was evaluated by immunohistochemistry. Pretreatment with erdosteine and pretreatment with N-acetylcysteine at a dose of 10 mg kg,1 had no protective effect on LPS-induced lung injury. When the doses of drugs increased, the severity of the lung damage caused by LPS decreased. It was found that as the pretreatment dose of erdosteine was increased, the rate of apoptosis induced by LPS in lung epithelial cells decreased and this decrease was statistically significant in doses of 300 mg kg,1 and 500 mg kg,1. Pretreatment with N-acetylcysteine up to a dose of 500 mg kg,1 did not show any significant effect on apoptosis regulation. It was noticed that both antioxidants had no significant effect on the local production level of TNF- ,. These findings suggest that erdosteine could be a possible therapeutic agent for acute lethal lung injury and its mortality. Copyright © 2006 John Wiley & Sons, Ltd. [source] Attenuation of half sulfur mustard gas-induced acute lung injury in ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2006Shannon D. McClintock Abstract Airway instillation into rats of 2-chloroethyl ethyl sulfide (CEES), the half molecule of sulfur mustard compound, results in acute lung injury, as measured by the leak of plasma albumin into the lung. Morphologically, early changes in the lung include alveolar hemorrhage and fibrin deposition and the influx of neutrophils. Following lung contact with CEES, progressive accumulation of collagen occurred in the lung, followed by parenchymal collapse. The co-instillation with CEES of liposomes containing pegylated (PEG)-catalase (CAT), PEG-superoxide dismutase (SOD), or the combination, greatly attenuated the development of lung injury. Likewise, the co-instillation of liposomes containing the reducing agents, N-acetylcysteine (NAC), glutathione (GSH), or resveratrol (RES), significantly reduced acute lung injury. The combination of complement depletion and airway instillation of liposomes containing anti-oxidant compounds maximally attenuated CEES-induced lung injury by nearly 80%. Delayed airway instillation of anti-oxidant-containing liposomes (containing NAC or GSH, or the combination) significantly diminished lung injury even when instillation was delayed as long as 1 h after lung exposure to CEES. These data indicate that CEES-induced injury of rat lungs can be substantially diminished by the presence of reducing agents or anti-oxidant enzymes delivered via liposomes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Combined pulmonary toxicity of cadmium chloride and sodium diethyldithiocarbamateJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001Erzsébet Tátrai Abstract The pulmonary toxicity of sodium diethyldithiocarbamate and cadmium chloride, each separately and in combination, was compared in Sprague-Dawley rats after single intratracheal instillation in sequential experiments by chemical, immunological and morphological methods. With combined exposure, the cadmium content of the lungs increased permanently relative to that of the lungs of just cadmium-treated animals. Immunoglobulin levels of the whole blood did not change, whereas in bronchoalveolar lavage the IgA and IgG levels increased significantly. Morphological changes were characteristic of the effects of cadmium but were more extensive and more serious than in the case of cadmium administration alone: by the end of the first month, interstitial fibrosis, emphysema and injury of membranes of type I pneumocytes developed and hypertrophy and loss of microvilli in type II pneumocytes were detectable. These results showed that although dithiocarbamates as chelating agents are suitable for the removal of cadmium from organisms, they alter the redistribution of cadmium within the organism, thereby increasing the cadmium content in the lungs, and structural changes are more serious than observed upon cadmium exposure alone. Copyright © 2001 John Wiley & Sons, Ltd. [source] Experimental Efficacy of Pericardial Instillation of Anti-inflammatory Agents during Percutaneous Epicardial Catheter Ablation to Prevent Postprocedure PericarditisJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2007ANDRE D'AVILA M.D. Introduction: Pericarditis is a potential complication of catheter-based percutaneous epicardial mapping and ablation. This study evaluates the efficacy and safety of intrapericardial instillation of anti-inflammatory agents after pericardial mapping and ablation in a porcine model of postprocedural pericarditis. Methods and Results: Twenty-five healthy swine underwent epicardial mapping and ablation after transthoracic subxyphoid puncture. After 60 minutes of continuous catheter manipulation in the pericardial space, radiofrequency energy was delivered in a linear fashion to the epicardial surfaces of both atria. The animals were randomly divided to receive the anti-inflammatory agents, Hyaluronic Acid and Triamcinolone, or control. Fourteen days after ablation, the hearts were excised and the degree of pericardial reaction/adhesions scored. The severity was uniformly graded 4 (intense) in all control animals and was characterized by intense adhesion between the parietal and the visceral pericardium obscuring tissue planes and epicardial anatomy. Hyaluronic Acid provided a mild benefit (score 3.0 ± 0.9), but 2 mg/kg of Triamcinolone significantly attenuated the inflammatory effect (all animals uniformly scored 1.0). Conclusion: In a porcine model of ablation-related pericarditis, intrapericardial instillation of 2 mg/kg of intermediate-acting corticosteroids effectively prevents post-procedure inflammatory adhesion formation. [source] A novel immunotherapy for superficial bladder cancer by intravesical immobilization of GM-CSFJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010Zhiming Hu Abstract In situ gene therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) was demonstrated to successfully inhibit tumour cell growth in a mouse orthotopic bladder cancer model, but suffered from several disadvantages, such as limited efficiency for gene delivery, low expression efficiency of the transgene and the safety concern resulting from viral vector. In order to address the limits, a novel immunotherapy was developed attentively through immobilization of streptavidin-tagged bioactive GM-CSF on the biotinylated mucosal surface of bladder wall on the basis of both the unique property of streptavidin (SA) to bind rapidly and almost irreversibly to any biotin-linked molecule and the outstanding ability of biotin to be incorporated easily into the proteins on the cell surface. The mouse orthotopic model of MB49 bladder cancer was used to evaluate the feasibility and efficacy of the novel immunotherapy performed twice a week for 3 weeks. Briefly, 1 day after intravesical implantation of 1 × 106 MB49 tumour cells in C57BL/6 mouse, 100 ,l of 1 mg/ml NHS-PEO4-biotin was instilled and allowed to incubate in the bladder for 30 min., followed by intravesical instillation of 100 ,l of 0.15 mg/ml SA-GM-CSF bifunctional fusion protein and incubation for 1 hr. SA-GM-CSF fusion protein was shown to be immobilized efficiently and durably on the biotinylated mucosal surface of bladder wall. The bladder cancer incidence was dramatically decreased from 100% in the control group to 37.5% in the SA-GM-CSF group. Importantly, 70% of the SA-GM-CSF-cured mice were protected against a second intravesical wild-type MB49 tumour challenge, indicating that an effective anti-tumour immunity was generated against MB49 bladder cancer. Thus, the novel immunotherapy may be an attractive therapeutic alternative and should be evaluated in bladder cancer patients. [source] | |||||||||||||||||||||||||||||||||||||