Macroscopic Tissue Damage Research Articles

Crotoxin from Crotalus durissus terrificus is able to down-modulate the acute intestinal inflammation in mice.

Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a local anti-inflammatory profile in mice.

Inhibition of the interleukin-23/interleukin-17 pathway by anti-interleukin-23p19 monoclonal antibody attenuates 2,4,6-trinitrobenzene sulfonic acid-induced Crohn's disease in rats.

The interleukin (IL)-23/IL-17 pathway is considered to be important in the pathogenesis of Crohn's disease (CD). The present study aimed to evaluate the effects of targeting the IL‑23/IL‑17 pathway using the anti-IL-23p19 monoclonal antibody (mAb) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD rats. A total of 60 Sprague-Dawley rats were randomly divided into a control group, model group and an anti-IL-23p19 mAb treatment group (administered intramuscularly every week at a dose of 1 ml/mg). Disease activity index (DAI), colon macroscopic damage index (CMDI) and tissue damage index (TDI) were then evaluated. The mRNA expression of IL-23p19, p40 (IL-23/12), retinoic acid-related orphan receptor-γt (ROR‑γt) and IL‑17 in colonic tissues were detected by reverse transcription‑polymerase chain reaction and levels of serum IL-23p19, p40, ROR-γt and IL-17 were measured using an enzyme‑linked immunosorbent assay. Anti‑IL‑23p19 mAb was found to effectively attenuate colonic inflammation demonstrated by reduced DAI, CMDI and TDI scores, improvement in pathological evaluation and downregulation of expression levels of IL‑23p19, p40 (IL-23/12), ROR-γt and the downstream proinflammatory cytokine, IL-17. Anti-IL-23p19 mAb attenuated TNBS-induced CD in model rats. The possible underlying mechanisms may be associated with inhibition of the IL-23/IL-17 pathway by inhibiting the expression of IL‑23p19 and downregulating the downstream proinflammatory cytokine IL‑17. Targeting the IL-23/IL-17 pathway may be a relevant and realistic therapeutic approach for the development of additive and alternative treatments to the biologics currently available in the treatment of CD.

The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy.

Background:An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model.Methods:Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein.Results:Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months.Conclusions:The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.

Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.

Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein-linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.

Three Potential Mechanisms for Failure of High Intensity Focused Ultrasound Ablation in Cardiac Tissue

High intensity focused ultrasound (HIFU) has been introduced for treatment of cardiac arrhythmias because it offers the ability to create rapid tissue modification in confined volumes without directly contacting the myocardium. In spite of the benefits of HIFU, a number of limitations have been reported, which hindered its clinical adoption. In this study, we used a multimodal approach to evaluate thermal and nonthermal effects of HIFU in cardiac ablation. We designed a computer controlled system capable of simultaneous fluorescence mapping and HIFU ablation. Using this system, linear lesions were created in isolated rabbit atria (n=6), and point lesions were created in the ventricles of whole-heart (n=6) preparations by applying HIFU at clinical doses (4-16 W). Additionally, we evaluate the gap size in ablation lines necessary for conduction in atrial preparations (n=4). The voltage sensitive dye di-4-ANEPPS was used to assess functional damage produced by HIFU. Optical coherence tomography and general histology were used to evaluate lesion extent. Conduction block was achieved in 1 (17%) of 6 atrial preparations with a single ablation line. Following 10 minutes of rest, 0 (0%) of 6 atrial preparations demonstrated sustained conduction block from a single ablation line. Tissue displacement of 1 to 3 mm was observed during HIFU application due to acoustic radiation force along the lesion line. Additionally, excessive acoustic pressure and high temperature from HIFU generated cavitation, causing macroscopic tissue damage. A minimum gap size of 1.5 mm was found to conduct electric activity. This study identified 3 potential mechanisms responsible for the failure of HIFU ablation in cardiac tissues. Both acoustic radiation force and acoustic cavitation, in conjunction with inconsistent thermal deposition, can increase the risk of lesion discontinuity and result in gap sizes that promote ablation failure.

BİR ERGENDE KOMPULSİF TARZDA SENKOP ATAKLARIYLA OLUŞTURULAN KENDİNE ZARAR VERME DAVRANIŞI

In this case report, self-harming behavioural pattern with recurrent syncope episodes in a 15 years old adolescent has been reviewed. In self-harm behavior, tissue damage can often be seen macroscopically. Whereas in this case, the extraordinary situation is possibility of occurrence of the hypoxic encephalopathyc changes with syncope episodes created by the patient, without macroscopic tissue damage.

Extracts of the Rat Tapeworm,Hymenolepis diminuta, Suppress Macrophage ActivationIn Vitroand Alleviate Chemically Induced Colitis in Mice

Analysis of parasite-host interactions can reveal the intricacies of immunity and identify ways to modulate immunopathological reactions. We assessed the ability of a phosphate-buffered saline-soluble extract of adult Hymenolepis diminuta to suppress macrophage (human THP-1 cell line, murine peritoneal macrophages) activity in vitro and the impact of treating mice with this extract on colitis induced by dinitrobenzene sulfonic acid (DNBS). A high-molecular-mass fraction of adult H. diminuta (HdHMW) or excretory/secretory products reduced macrophage activation: lipopolysaccharide (LPS)-induced interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) and poly(I:C)-induced TNF-alpha and IL-6 were suppressed by HdHMW. The active component in the HdHMW extract was minimally sensitive to boiling and trypsin digestion, whereas the use of sodium metaperiodate, as a general deglycosylation strategy, indicated that the immunosuppressive effect of HdHMW was at least partially dependent on a glycan: treating the HdHMW with neuraminidase and alpha-mannosidase failed to inhibit its blockade of LPS-induced TNF-alpha production by THP-1 macrophages. Mice treated with DNBS developed colitis, as typified by wasting, shortening of the colon, macroscopic and microscopic tissue damage, and an inflammatory infiltrate. Mice cotreated with HdHMW (three intraperitoneal injections) displayed significantly less inflammatory disease, and this was accompanied by reduced TNF-alpha production and increased IL-10 and IL-4 production by mitogen-stimulated spleen cells. However, cotreatment of mice with neutralizing anti-IL-10 antibodies had only a minor impact on the anticolitic effect of the HdHMW. We speculate that purification of the immunosuppressive factor(s) from H. diminuta has the potential to lead to the development of novel immunomodulatory drugs to treat inflammatory disease.

Differential adipokine response in genetically predisposed lean and obese rats during inflammation: a role in modulating experimental colitis?

The relationship between a predisposition to obesity and the development of colitis is not well understood. Our aim was to characterize the adipokine response and the extent of colitis in diet-induced obese (DIO) rats. DIO and control, diet-resistant (DR) animals were administered either saline or trinitrobenzene sulfonic acid (TNBS) to induce colitis. Macroscopic damage scores and myeloperoxidase (MPO) activity were measured to determine the extent of inflammation. Trunk blood was collected for the analysis of plasminogen activator inhibitor-1 (PAI-1) as well as leptin, ghrelin, and adiponectin. Colonic epithelial physiology was assessed using Ussing chambers. DIO rats had a modestly increased circulating PAI-1 before TNBS treatment; however, during colitis, DR animals had more than a fourfold increase in circulating PAI-1 compared with DIO rats. Circulating leptin was higher in DIO rats compared with DR animals, in the inflamed and noninflamed states. These changes in TNBS-induced adipokine profile were accompanied by decreased macroscopic tissue damage score in DIO animals compared with DR tissues. Furthermore, TNBS-treated DR animals lost significantly more weight than DIO rats during active inflammation. Colonic epithelial physiology was comparable between groups, as was MPO activity. The factors contributing to the decreased colonic damage are almost certainly multifold, driven by both genetic and environmental factors, of which adipokines are likely to play a part given the increasing body of evidence for their role in modulating intestinal inflammation.

Use of combined conventional and quantitative MRI to quantify pathology related to cognitive impairment in multiple sclerosis

Background:Cognitive impairment is one of the frequent and early findings in multiple sclerosis (MS).Objective:To determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage in...

Debridement of Cancellous Bone: A Comparison of Irrigation Methods

This study tests the bone debridement efficacy and damage to cancellous bone produced by different wound irrigation methods. Cancellous bone slices of bovine distal femurs (3 cm x 3 cm) were divided into eight test groups and scored with a saw in a latticed pattern. Four test groups were contaminated with 1.0 g rock dust and four were not. The specimens were then treated as follows: no treatment (control), bulb irrigation, brush-suction irrigation, or high-pressure pulsatile lavage (HPPL). Runoff from the irrigation was collected, filtered, lyophilized, and ashed to allow for quantitative determination of organic and inorganic material removed from the bone by each irrigation method. The bone samples were subjected to blinded grading on two five-point scales to assess: 1) macroscopic tissue damage and 2) amount of contaminant remaining following treatment. Significantly more (P < or = 0.05) mean organic material was removed from samples treated with HPPL (744.8 +/- 120.0 mg) than with bulb syringe (115.2 +/- 11.9 mg) or brush-suction irrigation (95.1 +/- 9.2 mg). Brush-suction irrigation removed statistically significantly more (P < or = 0.05) of the 1.0 g of initial inorganic contaminant (937.7 +/- 6.3 mg) than bulb syringe irrigation (866.2 +/- 30.1 mg), while HPPL (900.2 +/- 19.0 mg) did not. Past studies have shown HPPL to damage both soft tissue and bone structure. The tissue damage that HPPL produces has been accepted in the past in exchange for its presumed superiority in contaminant removal. In this study, HPPL damaged samples more than other irrigation methods by removing significantly more organic material from them. However, HPPL and bulb syringe removed a statistically similar amount of inorganic contaminant, while brush-suction irrigation removed a significantly greater amount of inorganic contaminant than bulb syringe. It is proposed that HPPL may drive some contaminants deeper into the tissue rather than removing them, rendering HPPL not only more deleterious to bone structure and healing, but also less efficacious at removing contaminant than brush-suction irrigation.

Neonatal immune challenge exacerbates experimental colitis in adult rats: potential role for TNF-α

Early life events and childhood infections have been associated with the development and onset of inflammatory bowel disease in adulthood. However, the consequences of neonatal infection in the development and severity of colitis are not established. We investigated the effects of a neonatal (postnatal day 14) or juvenile (postnatal day 28) immune challenge with LPS on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced damage and weight loss, as well as on food intake and body temperature in adult rats. Neonatally (n)LPS-treated rats developed more severe colitis than control animals, reflected in a greater loss of weight and a significantly increased macroscopic tissue damage score. These findings were associated with a hypothermic response after TNBS treatment in nLPS rats, but not in neonatally saline-treated rats receiving TNBS. These differences were not seen after TNBS in rats that had received LPS on postnatal day 28. Plasma corticosterone was measured as an index of adult hypothalamic-pituitary-adrenal (HPA) axis activation as was TNF-alpha, a proinflammatory cytokine associated with inflammatory bowel disease. Four days after TNBS treatment, plasma corticosterone was unaltered in all groups; however, TNF-alpha was significantly increased in adult TNBS-treated rats that had LPS as neonates compared with all other groups. In conclusion, neonatal, but not later, exposure to LPS produces long-term exacerbations in the development of colitis in adults. This change is independent of HPA axis activation 4 days after TNBS treatment but is associated with increased circulating TNF-alpha, suggestive of an exaggerated immune response in adults exposed to neonatal infection.

Effects of contrast agent infusion rates on thresholds for tissue damage produced by single exposures of high-intensity ultrasound

Stabilized microbubble ultrasound contrast agents (UCA) have potential to aid tissue ablation during ultrasound surgery by enhancing both cavitational and thermal damage mechanisms. Previously, we showed UCA infused at a rate of 1 microL/kg/min prior to ultrasound exposure could reduce the total energy required to produce tissue damage by up to two orders of magnitude. In this paper, we evaluate thresholds for macroscopic tissue damage with UCA infusion rates (IR) of 0.1, 0.3, 1, 3, and 10 microL/kg/min to determine IR potentially effective for ultrasound therapy. Canine kidneys were surgically externalized and insonified with single exposures of focused ultrasound. Incident exposures were 1.44 MHz tone bursts, either 250 ms in duration with intensity between 500 W/cm2 and 3200 W/cm2, or 100 micros to 1 s in duration with intensity equal to 3200 W/cm2. Probabilities of tissue damage occurrence were determined for each set of exposure conditions (intensity, duration, and IR). A threshold intensity and threshold duration, defined as the quantities for which tissue damage occurred with probability equal to 0.5, were estimated for each IR. Results show that, as IR increased from 0.1 to 10 microL/kg/min, the threshold intensity decreased by up to a factor of 3, and threshold duration decreased by up to a factor of 200. Microbubble introduction at IR up to 10 microL/kg/min thus may be effective in aiding ultrasound therapy.

Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis

Objectives: To establish the frequency of cognitive impairment in a population based sample of patients with recently diagnosed relapsing-remitting multiple sclerosis (RRMS), and to determine the relation between cognitive abnormalities...

Voxel‐based analysis of MTR images: A method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis

To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease.

A theoretical analysis of damage evolution in skeletal muscle tissue with reference to pressure ulcer development.

A theoretical analysis of damage evolution in skeletal muscle tissue with reference to pressure ulcer development.

Ultrasound imaging of Nd:YAG laser-induced tissue coagulation in porcine livers.

Absorption of laser light energy induces denaturation of proteins and thermocoagulation of irradiated tissue. Recently, MRI-guided laser coagulation in combination with MR thermometry was reported as a treatment of liver tumours. In the present study ultrasonographic imaging was evaluated for its suitability in laser induced tissue thermocoagulation. Fresh porcine livers were used for ex vivo examinations. Placement of the laser catheter and tissue coagulation during laser light emission were online monitored by ultrasonography. Nd:YAG laser-induced tissue damage was evaluated by macroscopical and microscopical examinations of histological sections. During laser light emission a marked hyperdense signal enhancement was observed by ultrasonography which strongly correlated with the extent of macroscopic tissue damage. The size of laser-induced coagulation zone depended on both the power setting and total energy delivered. Carbonization of the tissue surrounding the laser tip is a limiting factor because of laser light absorption. However our data indicate that using appropriate laser energy and exposure time prevent carbonization although carbonization can not be visualized by ultrasonography. It is concluded from the present ex vivo studies that laser coagulation can be effectively performed under ultrasonographic guidance.

Mycophenolate mofetil reduces tissue damage and inflammation in an experimental model of colitis in rats.

Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats. Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n = 10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prior to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes. Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P = 0.01). Microscopic ulcerations were reduced by 64% compared to controls (P = 0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes. Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases.

Mycophenolate Mofetil Reduces Tissue Damage and Inflammation in an Experimental Model of Colitis in Rats

Background: Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats. Methods: Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n=10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n=10) was treated with MMF at the same dose 2 days, 1 day and 1 h prior to induction of colitis. Control animals (n=10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes. Results: Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P=0.01). Microscopic ulcerations were reduced by 64% compared to controls (P=0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes. Conclusion: Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases.

Laparoscopic treatment of common bile duct stones by pulsed dye laser combined with optical feedback regulation: Phantom experiments using the bovine biliary tract

SummaryA pulsed dye laser lithotripter with optical feedback regulation was tested during experimental laparoscopic treatments for common bile duct stones using human bile stones and the bovine biliary tract fixed in a laparos-copy trainer. Laser pulses were delivered through a thin flexible choledocho-scope advanced via the cystic duct. Stone fragments were dislocated into the duodenum through the papilla Vater by the choledochoscope. A total of 20 litho-tripsies was successful, with a total number of pulses of 769 ± 530 (mean ± sd), total energy of 59.7 ± 46.0J and time of 41.7 ± 15min required per stone. In all 20 cases no macroscopic tissue damage in the common duct wall was detected. An additional experiment was carried out to prove that the porcine gall-bladder wall can be severely damaged by laser pulses without optical feedback regulation, whereas it is almost intact when lasered with optical feedback regulation. Our results suggest the pulsed dye laser lithotripter combined with optical feedback ...