Differences In Pathological Changes Research Articles

Early Contrast-Enhanced MR for Diagnosing Complete Tumor Response of Locally Advanced Esophageal Squamous Cell Carcinoma After Neoadjuvant Therapy: A Retrospective Comparative Study.

This study assessed the performance of early contrast-enhanced magnetic resonance (ECE-MR) in the detecting of complete tumor response (ypT0) in patients with esophageal squamous cell carcinoma following neoadjuvant therapy. Preoperative MR images of consecutive patients who underwent neoadjuvant therapy and surgical resection were reviewed retrospectively. The accuracy of ECE-MR and T2WI+DWI was evaluated by comparing the findings with pathological results. Receiver operating characteristic curve analysis was used to assess the diagnostic performance, and DeLong method was applied to compare the areas under the curves (AUC). Chi-squared analysis was conducted to explore the difference in pathological changes. A total of 198 patients (mean age 62.6 ± 7.8 years, 166 men) with 201 lesions were included. The AUC of ECE-MR was 0.85 (95% CI 0.79-0.90) for diagnosing ypT1-4, which was significantly higher than that of T2WI+DWI (AUC 0.69, 95% CI 0.63-0.76, p < 0.001). The diagnostic performance of both T2WI+DWI and ECE-MR improved with increasing tumor stage. The AUCs of ECE-MRI were higher in ypT1 and ypT2 tumors than T2WI+DWI. Degree 2-3 tumor-infiltrating lymphocytes and neutrophils were commonly seen in ypT0 tumors misdiagnosed by ECE-MR. Visual evaluation of ECE-MR is a promising diagnostic protocol for the detection of complete tumor response, especially for differentiation with early stage tumors. The accurate diagnosis of complete tumor response after neoadjuvant therapy using imaging modalities is of important significance for clinical decision-making for patients with esophageal squamous cell carcinoma. It is hoped that early contrast-enhanced MR will provide supportive advice for the development of individualized treatment options for patients.

The effects of the tropomyosin cardiomyopathy mutations on the calcium regulation of actin-myosin interaction in the atrium and ventricle differ

The molecular mechanisms of pathogenesis of atrial myopathy associated with hypertrophic (HCM) and dilated (DCM) mutations of sarcomeric proteins are still poorly understood. For this, one needs to investigate the effects of the mutations on actin-myosin interaction in the atria separately from ventricles. We compared the impact of the HCM and DCM mutations of tropomyosin (Tpm) on the calcium regulation of the thin filament interaction with atrial and ventricular myosin using an in vitro motility assay. We found that the mutations differently affect the calcium regulation of actin-myosin interaction in the atria and ventricles. The DCM E40K Tpm mutation significantly reduced the maximum sliding velocity of thin filaments with ventricular myosin and its Ca2+-sensitivity. With atrial myosin, its effects were less pronounced. The HCM I172T mutation reduced the Ca2+-sensitivity of the sliding velocity of filaments with ventricular myosin but increased it with the atrial one. The HCM L185R mutation did not affect actin-myosin interaction in the atria. The results indicate that the difference in the effects of Tpm mutations on the actin-myosin interaction in the atria and ventricles may be responsible for the difference in pathological changes in the atrial and ventricular myocardium.

ATF3-Expressing Large-Diameter Sensory Afferents at Acute Stage as Bio-Signatures of Persistent Pain Associated with Lumbar Radiculopathy.

The mechanism of pain chronicity is largely unknown in lumbar radiculopathy (LR). The anatomical location of nerve injury is one of the important factors associated with pain chronicity of LR. Accumulating evidence has shown constriction distal to the dorsal root ganglion (DRG) caused more severe radiculopathy than constriction proximal to the DRG; thereby, the mechanism of pain chronicity in LR could be revealed by comparing the differences in pathological changes of DRGs between nerve constriction distal and proximal to the DRG. Here, we used 2 rat models of LR with nerve constriction distal or proximal to the DRG to probe how the different nerve injury sites could differentially affect pain chronicity and the pathological changes of DRG neuron subpopulations. As expected, rats with nerve constriction distal to the DRG showed more persistent pain behaviors than those with nerve constriction proximal to the DRG in 50% paw withdraw threshold, weight-bearing test, and acetone test. One day after the operation, distal and proximal nerve constriction showed differential pathological changes of DRG. The ratios of activating transcription factor3 (ATF3)-positive DRG neurons were significantly higher in rats with nerve constriction distal to DRG than those with nerve constriction proximal to DRG. In subpopulation analysis, the ratios of ATF3-immunoreactivity (IR) in neurofilament heavy chain (NFH)-positive DRG neurons significantly increased in distal nerve constriction compared to proximal nerve constriction; although, both distal and proximal nerve constriction presented increased ratios of ATF3-IR in calcitonin gene-related peptide (CGRP)-positive DRG neurons. Moreover, the nerve constriction proximal to DRG caused more hypoxia than did that distal to DRG. Together, ATF3 expression in NHF-positive DRG neurons at the acute stage is a potential bio-signature of persistent pain in rat models of LR.

REDUCED CHICKEN EMBRYO DWARFING EFFECT IS RELATED TO INFECTIOUS BRONCHITIS VIRUS TW2575/98 REPLICATION EFFICIENCY

An attenuated infectious bronchitis virus (TW2575/98) vaccine strain was successfully developed after 75 serial passages in embryonated chicken eggs. However, the in ovo vaccination for disease control was not applied in practice because this vaccine strain is highly pathogenic to chicken embryos (CEs) causing early death, dwarfing and other harmful effects. We compared the differences in virus replication, pathological changes, and tissue tropism between the wild virus and attenuated vaccine strain in CEs inoculated with different viral titer levels, i.e. 0.1, 1 and 10 EID[Formula: see text]/egg. The wild virus caused dwarfing effect at high titer inoculation, whereas the attenuated vaccine strain caused the dwarfing effect only at a lower viral inoculation accompanied by the earlier infection establishment and embryonic death at high and medium titers. There were no significant differences in the pathological changes in CEs infected by both wild and attenuated strains. Detected by immunohistochemistry, the viral antigens of both strains could be found mainly at the epithelium of the chorioallantoic membrane, lung parabronchus, renal tubules and some in the spleen and heart serosa. These findings indicated that the early embryonic death and dwarfing is not related to the change in cell/tissue tropism of the vaccine strain, rather on the early infection establishment and viral load. We suggest that the vaccine strain inoculated titer could be adjusted to an optimal low level for in ovo vaccination to overcome the poor hatching rate for its higher virulence to chicken embryos.

Differences in pathological changes between two rat models of severe traumatic brain injury.

The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans, while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters. In this study, we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences. The severe controlled cortical impact model was produced by an electronic controlled cortical impact device, while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube. Body temperature and mortality were recorded, and neurological deficits were assessed with the modified neurological severity score. Brain edema and blood-brain barrier damage were evaluated by assessing brain water content and Evans blue extravasation. In addition, a cytokine array kit was used to detect inflammatory cytokines. Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining. Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations. More severe motor dysfunction was observed in the severe controlled cortical impact model, while more severe cognitive dysfunction was observed in the severe free weight drop model. Brain edema, inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group. The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage, with higher mortality and lower repeatability compared with the severe controlled cortical impact group. Severe brainstem damage was not found in the severe controlled cortical impact model. These results indicate that the severe controlled cortical impact model is relatively more stable, more reproducible, and shows obvious cerebral pathological changes at an earlier stage. Therefore, the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury, while the severe free weight drop model may be more apt for studies on diffuse axonal injury. All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University, China (approval No. IRB2012-028-02) in February 2012.

Identification of paraquat-induced lung injury and fibrosis in mice using intraperitoneal injection in different dose and exposure time

Objective To explore the effect of paraquat (PQ) on lung injury and fibrosis in mice by using intra-peritoneal administration of different doses and different lengths of exposure time, as well as to establish a more appropriate animal model of lung injury and related fibrosis in a simple operation with favorable reproducibility. Methods Male C57BL/6J mice of 8-10 weeks in the model group were intra-peritoneally administered with different paraquat doses for different lengths of exposure time. There were three fashions of giving PQ: single dosing with different doses (40 mg/kg, 50 mg/kg, or 60 mg/kg), successive dosing every day for 5 d with different doses (10 mg/kg, 12.5 mg/kg, or 15 mg/kg) or intermittent dosing every 4 d for 4 occasions with different doses (20 mg/kg, 22.5 mg/kg, or 25 mg/kg), respectively. Control animals (randomly selected) received an equal volume of saline instead at the same time. Mice were sacrificed at 1 week or 2 weeks after the last exposure. The general physical condition of mice including body weight as well as mortality was monitored daily. Lung static compliance measurement, bronchoalveolar lavage (BAL) fluid samples for cytospin analysis, hydroxyproline assay, and whole left lung sections stained for histological analysis were obtained. Results Both single dosing method and intermittent dosing method with different doses of paraquat could induce acute lung injury in some of mice. The inflammation changes became more serious as the dose increased during the early observation. While during the late observation, the pulmonary fibrosis was found in only a few survival mice. The pathological section showed the fibrotic lesions were mainly found in posterior portion, sub-pleural and peripheral portions of lung. However, the mortality was high in these two methods during early lung injury stage, and lower morbidity of pulmonary fibrosis in late stage. The successive dosing strategy didn’t produced significant differences in pathological changes in lung of mice between different intervals of observation. Conclusion Single dosing with high dosage or intermittent dosing with moderate dosage as a systemic administration strategy was necessary for intra-peritoneal PQ to induce mice acute lung injury. However, the model with low morbidity of pulmonary fibrosis and high mortality during acute injury stage was unsatisfactory one. PQ administration with successive lower doses strategy was not sufficient to induce lung injury as well as pulmonary fibrosis in C57BL/6J mice. Key words: Paraquat; Intraperitoneal injection; Lung injury; Pulmonary fibrosis; Animal model

Effect of docosahexaenoic acid on hepatic ischemia-reperfusion injury in rats

Objective To evaluate the effect of docosahexaenoic acid(DHA)on hepatic ischemia-reperfusion(I/R)injury in rats. Methods Fifteen male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were randomly divided into 3 groups(n=5 each)using a random number table: sham operation group(group S), hepatic I/R group(group I/R), and group DHA.Hepatic I/R was induced by clamping the hepatic pedicle supplying the left and middle lobes of the liver for 60 min, followed by 24 h reperfusion in anesthetized rats.DHA 4 mg/kg was injected intravenously at 30 min before ischemia and 10 min of reperfusion in group DHA.The equal volume of solvent was given instead in S and I/R groups.Blood samples were taken from the inferior vena cava at 24 h of reperfusion for determination of serum alanine aminotransferase(ALT), and aspartate aminotransferase(AST)activities, and resolvin D1 concentrations.The rats were then sacrificed, and the livers were removed for determination of myeloperoxidase(MPO)activity(by spectrophotometry), and interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)mRNA expression(by quantitative real-time reverse transcriptase polymerase chain reaction). The livers were cut into sections which were stained with haematoxylin and eosin, and examined under light microscope. Results Compared to group S, the serum ALT and AST activities, serum resolvin D1 concentrations, and MPO activity, and IL-6 and TNF-α mRNA expression in liver tissues were significantly increased in I/R and DHA groups(P 0.05). There was no significant difference in pathological changes of the liver between group DHA and group I/R. Conclusion DHA can attenuate inflammatory responses during hepatic I/R, but it is not sufficient to mitigate liver injury in rats. Key words: Docosahexaenoic acids; Reperfusion injury; Liver

Protective effects of ischemic postconditioning on intestinal mucosa barrier function in rabbits with crush injury of hind limb: an experimental study

Objective To explore the protective effects of two types of ischemic postconditioning (IP) on intestinal mucosa barrier in rabbits with crush injury of the hind limb. Methods This study was conducted between August and December 2008 in the Department of Trauma Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. The model of crush injury to the hind limb of rabbits was firstly developed by a 25 kg object with the right hind limbs fixed by wooden splints, and then two types of IP were established, including occluding/opening the common iliac artery and vein alternatively (traditional IP, IP A) and binding/loosening the proximum of the injured hind limb alternatively (modified IP, IP B). Thirty-six male New Zealand white rabbits were randomly divided into three groups: IP A group, IP B group and control group, with 12 rabbits in each group. The serum levels of diamine oxidase (DAO) and intestinal fatty acid-binding protein (I-FABP) were detected at 2, 6, 12 and 24 hours after injury. Pathological changes of ileum were examined at 24 hours after injury. Results The serum levels of I-FABP at 2, 6, 12 and 24 hours after injury in both IP A and IP B groups had a significant decrease, compared with control group. DAO levels also showed the same change trend at 2 and 6 hours after injury, but showed no significant difference between two IP groups. No difference in pathological changes of ileum was found among the three groups. Conclusions IP can protect intestinal mucosa barrier function on the model of hind limb crush injury in rabbits. Meanwhile the modified IP B shows the same protection as the traditional IP A, and is worth applying in clinic.

Chimeric vapA/groEL2 DNA vaccines enhance clearance of Rhodococcus equi in aerosol challenged C3H/He mice

Rhodococcus equi remains a significant bacterial pathogen, causing severe pyogranulomatous pneumonia in foals aged 1-3 months. There is no effective vaccine currently available for the prevention of R. equi pneumonia. DNA vaccines are known to offer specific advantages over conventional vaccines. The aim of this study was to demonstrate efficacy of our recombinant DNA vaccine candidates, namely pcDNA3-Re1, pcDNA3-Re3 and pcDNA3-Re5 by combining a heat shock protein GroEL2 to a virulence-associated protein A (VapA) from R. equi to protect C3H/He mice against the R. equi infection. VapA was shown to be strongly recognised by sera from pneumonic foals. All vaccines elicited at least a doubling of the IgG2a/IgG1 ratio in comparison to the controls, indicating a bias to the Th1 response, which is postulated to be crucial for bacterial clearance and protective immunity against intracellular pathogens including R. equi. In addition, the immunised mice showed a significant reduction in R. equi in their lungs at 7 days after the aerosol challenge in comparison to PBS treated mice. However, examination of lung pathology 14 days after the challenge showed no gross differences in pathological changes between the unvaccinated and vaccinated animals. The lack of significant pathological changes suggests that the precise level of protection against R. equi pneumonia in the murine model of infection may not represent a true effectiveness of the potential vaccine candidates, indicating the mouse may not be the ideal non-equine model for vaccine studies and (or) the incomplete immunogenic antigen of vapA-based DNA vaccine constructs that mount an inadequate cell-mediated immune response against the R. equi infection.

A guinea pig model of adhesive otitis media and the effect of tympanostomy

Objective: The pathophysiology and prevention strategies of adhesive otitis media were investigated using two animal otitis media models induced by the inoculation of a corrosive agent into the tympanic clefts of guinea pigs. Methods: In the first experiment, KANSUI (consisting of potassium carbonate and sodium carbonate) solution was injected into the left tympanic cleft of the guinea pigs. Five groups of five animals were sacrificed at 2 weeks, and at 1, 3, 6, and 12 months after inoculation to observe the pathological changes with time. In the second experiment, a similar otitis media model was induced in 18 guinea pigs. Tympanostomy was performed at 1 and 2 weeks after induction of the otitis media to eliminate inflammatory exudate from the tympanic cleft. Three groups of six animals were sacrificed at 1, 3, and 6 months after the tympanostomy to compare the differences in pathological changes between the groups with and without tympanostomy. Results: In the first experiment, severe mucosal injury to the middle ear mucosa was observed at 2 weeks, and at 1 and 3 months after inoculation, and the tympanic membrane (TM) had adhered to the promontorium at 3, 6 and 12 months after inoculation. In the second experiment, TM adhesion decreased following the tympanostomy. Conclusion: It is suggested that severe injury to the middle ear mucosa caused TM adhesion during the process of wound healing, and that tympanostomy is effective in preventing adhesive otitis media.

Quantitative evaluation of myocardial ultrastructure following hypothermic anoxic arrest

Thirty-six anesthetized mongrel dogs were subjected to systemic hypothermia and anoxic cardiac arrest while on cardiopulmonary bypass. Myocardial fine structure in the left ventricle was evaluated by quantitative analysis in the subepicardial, mid-myocardial, and subendocardial layers. The specimens were obtained by a transmural myocardial biopsy method. Graded hypothermia was employed at 36 degrees, 30 degrees, 28 degrees, 25 degrees, and 22 degrees C. The aorta was cross-clamped for 30 minutes at 36 degrees, 30 degrees, 28 degrees, and 25 degrees C. or for 45 minutes at 25 degrees and 22 degrees C. Observations indicated that pathological changes of the myocardial fine structure were significant after anoxic arrest in the normothermic group. Lesions were most extensive in the subendocardial layer after normothermic anoxic arrest, whereas hypothermia below 30 degrees C. preserved the myocardium throughout all layers without difference in pathological changes in the fine structure among the layers. Mitochondria and glycogen granules in the mid-myocardial layer and the subendocardial layer were best preserved with hypothermia at 25 degrees and 22 degrees C. after 30 minutes or 45 minutes of anoxic arrest, and dogs in these groups had a survival rate of 100 percent. Quantitative analysis of ultrastructural changes induced in these experiments suggest that a safe duration of anoxic arrest at 22 degrees to 25 degrees C. is between 30 and 45 minutes.

HISTOPATHOLOGIC STUDIES ON THE SALIVARY GLANDS OF RABIC DOGS

Since June, 1950 we have extracted and examined parotid and madibular glands from 15 cases of rabic clogs which occurred in Gurnma-ken, with the following results : (1) On parotid glands no remarkable degeneration or inflammatory changes were observed. There was generally noted atrophy.(2) On mandibular glands were observed interstitial inflammation with strong degeneration of eipthelium.(3) Interestitial inflammation developed diffusely or in scattered focuses and consisted in cell infiltration chiefly of lymphocytes, plasma cells and of some histiocytes. This reaction form is same as was observed on inflammatory focuses in the tissue of other organs of rabic dogs.(4) As for degenerative focuses were noted pictures of various stages ranging from vacuole and karyorrhexis to destruction of cellbodies.(5) The relation between the degeneration and interstitial inflammation of the mandibular glands cannot be said the sequence of the latter to the former as was reported by Orth, Gruber et al. We would rather regard it the interstitial inflammation accompanied by degeneration.(6) Negri's bodies could not be demonstrated.(7) We could not explain the cause of the remarkable difference in pathologic changes between the parotid and mandibular glands.