Early Histopathological Changes Research Articles

Cortical microstructural associations with CSF amyloid and pTau

Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer’s disease (AD) pathology. Few studies have evaluated multi-shell dMRI models such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau181 and Aβ1–42 burden and regional cortical NODDI and MAP-MRI indices in 46 cognitively unimpaired individuals, 18 with mild cognitive impairment, and two with dementia (mean age: 71.8 ± 6.2 years) from the Alzheimer’s Disease Neuroimaging Initiative. We compared findings to more conventional cortical thickness measures. Lower CSF Aβ1–42 and higher pTau181 were associated with cortical dMRI measures reflecting less hindered or restricted diffusion and greater diffusivity. Cortical dMRI measures, but not cortical thickness measures, were more widely associated with Aβ1–42 than pTau181 and better distinguished Aβ+ from Aβ- participants than pTau+ from pTau- participants. dMRI associations mediated the relationship between CSF markers and delayed logical memory performance, commonly impaired in early AD. dMRI metrics sensitive to early AD pathogenesis and microstructural damage may be better measures of subtle neurodegeneration in comparison to standard cortical thickness and help to elucidate mechanisms underlying cognitive decline.

Early histopathological changes of secondary degeneration in the spinal cord after total MCA territory stroke

Previous research has not demonstrated secondary degeneration of the spinal cord (SpC) motoneurons after cerebral infarct. The aim of the present study is to investigate the involvement of the anterior horn cells (AHC) in the early post-stroke period using histomorphological and immunohistochemical methods. Post-mortem analysis of the 6th cervical segment was performed in 7 patients who had total MCA stroke within 1 month before death. Nissl-stained sections were used for morphometry, while CD68 and synaptophysin (SYP) immunohistochemistry to monitor microglial activation and synaptic changes in the anterior horn (AH), respectively. Contralateral to the cerebral lesion (contralesional side), cells were smaller after 3 days and larger after 1 week of stroke, especially regarding the large alpha motoneurons. CD68 density increased mainly on the contralesional Rexed’s IX lamina of the SpC. SYP coverage of the large motoneurons was reduced on the contralesional side. Early microglial activation in the AH and electrophysiological signs has suggested the possibility of impairment of anterior horn cells (AHC-s). Our study supported that early microglial activation in the contralesional side of the SpC may primarily affect the area corresponding to the location of large motoneurons, and is accompanied by a transient shrinkage followed by increase in size of the large AHC-s with a reduction of their synaptic coverage. After MCA stroke, early involvement of the SpC motoneurons may be suspected by their morphological and synaptic changes and by the pattern of microglial activation.

Earliest histopathological changes in COVID-19 pneumonia with comprehensive gene expression analyses: A case series study.

In COVID-19 pneumonia, early detection and appropriate treatment are essential to prevent severe exacerbation. Therefore, it is important to understand the initiating events of COVID-19 pneumonia. However, at present, the literature about early stage disease has been very limited. Here, we investigated the earliest histopathological changes and gene expression profiles associated with COVID-19 pneumonia. We carefully examined 25 autopsied cases with different clinical courses. Dilation of capillaries and edematous thickening of the alveolar septa were found even in areas that macroscopically looked almost normal. Pneumocytes, histocytes/macrophages, and vascular endothelial cells were immunohistochemically positive for tissue factor, which is an important early responder to tissue injuries. Comprehensive gene expression analyses revealed that those lesions presented differential profiles compared to those of control lungs and were associated with a significant upregulation of the lysosomal pathway. Alveolar capillary dilation and edematous thickening may be the earliest histopathological change detected in COVID-19 pneumonia. Intensive investigations of such lesions may lead to an understanding of the initiating event of not only COVID-19 pneumonia but also of general diffuse alveolar damage.

Cortical Microstructure Mediates CSF Amyloid and Tau Associations with Episodic Memory Performance

AbstractBackgroundEpisodic memory impairment is common in early stages of Alzheimer’s disease (AD) and has been linked to atrophy in cortical regions that are vulnerable to AD neuropathological processes (e.g., amyloid and tau accumulation). Volumetric measures are relatively insensitive to microstructural brain changes that can occur in earlier disease stages. Microstructural properties of brain tissue can be non‐invasively assessed using advanced diffusion MRI (dMRI) models such as neurite orientation dispersion and density imaging (NODDI). While a number of studies have related white matter microstructure to AD pathology and memory, few have evaluated advanced dMRI indices in cortical gray matter where the earliest histopathological changes are thought to occur.MethodWe evaluated 66 ADNI participants (age 71.8±6.2 years; 25 Males; 46 CN/18 MCI/2 AD) with available MRI (T1‐weighted and multi‐shell diffusion) and CSF Aβ1–42, pTau181, and pTau181/Aβ1–42 data (Fig1A). Episodic memory was assessed using WMS‐R delayed logical memory scores (Del‐Mem). We estimated average NODDI ICVF, ECVF, ISOVF, and ODI (Fig1B) in an AD‐metaROI of cortical gray matter regions that are sensitive to early AD (Fig1C,D). We tested whether the effect of CSF biomarkers on Del‐Mem were mediated by metaROI measures (Fig2A), adjusting for age, sex, education, and MRI site as a grouping variable. For comparison, we re‐ran analyses with AD‐metaROI cortical thickness as the mediator.ResultLower CSF Aβ1–42 and higher pTau181/Aβ1–42 were significantly associated with lower Del‐Mem performance (FDR; q=0.05); pTau181 was not associated (Fig2B).Lower cortical ICVF, ODI, and thickness and higher ISOVF were associated both with lower Aβ1–42 and higher pTau181/Aβ1–42 (Fig2C).The effect of Aβ1–42 on Del‐Mem was fully mediated by ICVF. The effect of pTau181/Aβ1–42 on Del‐Mem was partially mediated by ISOVF. Del‐Mem was not mediated by ODI or thickness (Table1). Sensitivity analyses in the 64 non‐demented individuals revealed comparable results.ConclusionLower cortical ICVF and higher ISOVF with greater Aβ and pTau/Aβ burden, respectively, may indicate neuronal loss or edema. While both ICVF and ISOVF findings can be driven by reduced diffusion restriction, larger pTau/Aβ effects on episodic memory mediated through ISOVF may indicate that tau hyperphosphorylation and aggregation induces a greater degree of inflammation, neuronal dysfunction and death.

Patellar ligament desmopathy in the horse – a review and comparison to human patellar tendinopathy (‘Jumper’s knee’)

Patellar ligament desmopathy in horses is regarded as an uncommon condition with unclear aetiology. Of the three patellar ligaments in the horse, the intermediate is the one most often diagnosed with desmopathy in horses presenting with chronic lameness. This structure corresponds to the patellar tendon in humans. As diagnostic imaging modalities continuously improve, changes in echogenicity of the patellar ligaments are identified ultrasonographically with increasing frequency. However, disruption of the normal fibre pattern may be present also in patellar ligaments in horses that show no signs of lameness. Similarly, there is a poor correlation between pain and diagnostic imaging findings in human patellar tendinopathy. Consequently, there appears to be a knowledge gap pertaining to normal ultrasonographic variation and diagnostic criteria for disease of the patellar ligaments in horses. Furthermore, local anaesthetic techniques to verify the diagnosis are poorly described, and due to the low number of treated cases, no specific treatment modality can be recommended on a scientific basis. The aim of this paper is to review the current knowledge regarding the pathogenesis, diagnosis and management of patellar ligament desmopathy in horses, compare this condition with patellar tendinopathy in humans, and identify areas for further research to increase the diagnostic accuracy in horses. We conclude that there is a profound need for better descriptions of ultrasonographic variation and pathological changes of the equine patellar ligaments. Identification of areas of maximal ligament strain and descriptions of early histopathological changes could render more information on the possible aetiology, preventive measurements and treatment options of desmopathy. Description of regional innervation could aid in development of methods for diagnostic anaesthesia to verify pain originating from the ligaments.

Long-term safety of intraluminal spring-mediated bowel lengthening

PurposeThe purpose of the study is to examine the long-term safety of an endoluminal bowel lengthening device prior to its use in the first human trial. In addition, device performance and natural passage will be evaluated. MethodsEndoluminal lengthening springs were surgically placed into the jejunum of Yucatan minipigs using the Eclipse XL1 device. A matching internal control segment of jejunum was marked at the time of operation. Weekly weights and fluoroscopic studies were obtained to evaluate spring deployment and position until devices passed. Animals were euthanized at 28, 60, 90, and 180 days. At necropsy, length measurements were recorded, and histopathologic analysis was performed. ResultsThere were no bowel obstructions or overt perforations attributable to the device. All surviving animals gained weight and were clinically thriving. All devices passed out of the rectum by 180 days. Bowel lengthening was seen in all experimental segments, and minimal fibrosis was observed by 180 days. ConclusionJejunal lengthening persisted after device had passed through the intestinal tract after 180 days. Early histopathologic changes of the jejunum during distraction enterogenesis normalized over time.

Oral submucous fibrosis: Histopathological features with pathophysiologic correlations

Oral submucous fibrosis (OSMF) is a potentially malignant disorder characterized by juxtaepithelial inflammation and progressive fibrosis of submucosal tissues. It may affect any part of the oral cavity, as well as pharynx and oesophagus. The pathogenesis of OSMF may be attributable to habitual chewing of areca nut and its products, which is more prevalent amongst young population of South East Asia and India. Various histopathological features in different tissue components- epithelial, connective tissue stroma, muscle and salivary gland may be observed along the course of this chronic disorder. In connective tissue, extensive fibrosis with progressive hyalinization of collagen fibers and muscles accompanied by inflammatory response is considered to be pathognomonic feature. Advanced stages of OSMF may show atrophic changes or even dysplasia in the epithelium which may undergo malignant transformation. Malignant transformation rate of OSMF has been proved to be around 7.5%. Thus, identification of early histopathological changes in OSMF can lead to improved survival rates. The present article illustrates the various histopathological features observed during different stages of development of OSMF. A better understanding of the correlation between histopathological features and corresponding clinical manifestations can aid dental surgeons in prognostication of the lesion and determining response to treatment.

Early histopathologic changes in primary biliary cholangitis: does 'minimal change' primary biliary cholangitis exist? A pathologist's view.

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an autoimmune, slowly progressive, cholestatic liver disease characterized by nonsuppurative destructive cholangitis, and interlobular bile duct destruction. Necroinflammatory activities of the hepatic parenchyma and limiting plates of milder form along with late liver fibrosis may develop. Serum liver tests include elevated serum alkaline phosphatase along with a positive antimitochondrial antibody (AMA) in nearly 95% of patients. Liver biopsies are an important confirmatory and staging tool and are additionally very helpful when AMA is negative. More specifically, the earliest changes in liver biopsy suspicious for PBC can be detected, namely loss of the canals of Hering (CoH), as proposed by various authors recently. CoH loss has been described as an early feature of PBC. We focus on early histologic features of PBC, investigating through the literature the possible role of 'minimal change' supporting the clinical diagnosis of PBC, even in the absence of characteristic granulomatous duct destructive lesions.

X-ray microtomography is a novel method for accurate evaluation of small-bowel mucosal morphology and surface area

The often poorly orientated small-bowel mucosal biopsies taken for the diagnostics of celiac disease and other intestinal disorders are prone to misinterpretation. Furthermore, conventional histopathology has suboptimal sensitivity for early histopathological changes observed in short-term challenge studies. X-ray microtomography (micro-CT) is a promising new method for accurate imaging of human-derived biological samples. Here, we report that micro-CT could be utilized to create virtual reconstructions of endoscopically obtained intestinal biopsies. The formed digital 3D images enabled selection of always optimal cutting angles for accurate measurement of the mucosal damage and revealed diagnostic lesions in cases interpreted as normal with conventional histomorphometry. We also demonstrate that computer-assisted point cloud analysis can be used to calculate biologically meaningful surface areas of the biopsies in different stages of mucosal damage with excellent replicability and correlation with other disease parameters. We expect the improved diagnostic accuracy and capability to measure the surface areas to provide a powerful tool for the diagnostics of intestinal diseases and for future clinical and pharmaceutical trials.

Early effects of irradiation on laryngeal mucosa in a gastroesophageal reflux model: an experimental study.

The aim of this study was to evaluate the early histopathological changes of gastroesophageal reflux and irradiation on laryngeal mucosa in rats. Animal study. Experimental animal laboratory, tertiary referral center. Twenty-four adult female Wistar Albino rats were grouped as: control (n = 6), reflux and irradiation (n = 10), and irradiation (n = 8). Rats were operated to create a reflux model 30days before irradiation. Ionizing radiation was administered in a single fraction of a 20Gy to the larynx. Laryngeal tissue samples were taken at the 4th day of irradiation and all specimens underwent histopathological examination. Edema and vascular dilation in lamina propria were higher in the reflux and irradiation, and irradiation groups than control group. Inflammation was higher in the reflux and irradiation group than the control group. Inflammation in squamous epithelium was higher in the reflux and irradiation and irradiation groups compared to the control group. Inflammation in the squamous epithelium of the irradiation group was higher than the reflux and irradiation group. In the respiratory tract epithelium, inflammation was higher in the reflux and irradiation group; additionally, a significant loss of cilia was present in the reflux and irradiation and irradiation groups while pseudostratification was higher in the reflux and irradiation group. Ionizing radiation-induced inflammation may increase on previously inflammated area due to gastroesophageal reflux. Therefore, it may be helpful to investigate and treat the reflux in laryngeal cancer patients that will receive ionizing radiation.

Granulocyte Colony-Stimulating Factor Attenuates Blood-Brain Barrier Damage and Improves Cognitive Function in Spontaneously Hypertensive Rats.

Cerebral small vessel diseases (CSVDs) always coincide with endothelial dysfunction and blood-brain barrier (BBB) damage. However, the detailed mechanisms of CSVD are still unclear and the therapeutic efficacy is not so satisfaction. Granulocyte-colony stimulating factor (G-CSF) can play a neuroprotective role in many neurological diseases. We investigated whether G-CSF exerted positive effects on BBB protection and cognitive function improvement in spontaneously hypertensive rats (SHRs), a rat model displaying the early histopathological changes of CSVD. Twenty-four-week-old SHRs received daily administrations of either G-CSF (50µg/kg) or normal saline (NS) for 7 days. The novel object recognition test (NORT) was then conducted after treatment. After behavioral test, we examined IgG fluorescence staining to indicate BBB leakage. G-CSF receptor (G-CSFR), aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression were determined by immunofluorescence. The surface structure of endothelial cells was examined by scanning electron microscopy (SEM). G-CSF significantly attenuated IgG leakage and improved non-spatial memory in SHRs. G-CSFR was expressed at higher levels in both G-CSF-SHRs and NS-SHRs. The surface structural changed on the endothelial cells and expression of AQP-4 and GFAP decreased after G-CSF treatment. However, no significant differences in Claudin-5 expression were observed. These findings demonstrated that the administration of exogenous G-CSF can improve cognitive function in a model of CSVD, possibly due to the recovery of endothelial and BBB function.

MR elastography detection of early viscoelastic response of the murine hippocampus to amyloid β accumulation and neuronal cell loss due to Alzheimer's disease.

To investigate in vivo viscoelastic parameters related to early histopathological changes in the hippocampus and the cortex in early, preclinical Alzheimer's disease (AD) stages. Magnetic resonance elastography (MRE) was applied to female APP23 mice, an established transgenic mouse model of AD, at three different stages early in disease progression. To investigate the potential therapeutic effects of physical, cognitive, and social stimulation on brain viscoelasticity and histopathological characteristics, MRE was also applied after exposing young APP23 mice to environmentally enriched cage conditions (ENR), for 1, 12, or 24 weeks, which corresponds to adolescent, young-adult, and adult age at the time of analysis. Viscosity in the hippocampus of APP23 mice is lower than in controls (CTR) (P = 0.005) and does not increase with age, as in CTR mice (adolescent vs. young-adult: P = 1.000, vs. adult: P = 0.493, young-adult vs. adult: P = 1.000). Hippocampal cell numbers decrease with disease progression in APP23 mice (P < 0.001). Elasticity in the hippocampus is also reduced in APP23 mice (P = 0.024) but increases (P = 0.027) with disease progression. ENR in APP23 mice transiently increased hippocampal cell numbers (P = 0.002) but not viscosity (P = 0.838). MRE detects alterations in viscoelasticity in the hippocampus related to early histopathological changes in the APP23 mouse model of AD. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:105-114.

English

The present work was conducted to perform a short-term comparative analysis and evaluate the anti-neoplastic effects of diallyl disulfide on rectal carcinogenicity via histopathological changes, chromosomal aberrations, and mitotic index induced by 1,2-dimethylhydrazine on male rabbits (Orectolagus cuniculus). The histological changes that can be seen microscopically showed that 1,2-dimethylhydrazine at the suggested dose (20 mg/kg) produced significant alterations in rectal mucosa of 1,2-dimethylhydrazine group. The presence of dysplasia was regarded as an early histopathological changes in the precursor lesions of rectal cancer. Three varieties of intrachromosomal instability were detected, deletions (1p12, 15q23, 21q14), duplications (5q14; 13q23, 14q21) and ring (X) chromosome with a highly significant increase (P&lt;0.05) in comparison with control. Such aberrations were markedly inclined in 1,2- dimethylhydrazine group after treatment by diallyl disulfide and the pretreated group&nbsp; that received diallyl disulfide prior to 1,2-dimethylhydrazine injection with a significant decrease (P&lt;0.01). Mitotic index ranged from 46, 22, 17, and 18% to 20% in 1,2-dimethylhydrazine, 1,2-dimethylhydrazine +diallyl disulfide, diallyl disulfide, control, and pretreated diallyl disulfide +1,2-dimethylhydrazine groups, respectively. Examination of 1,2-dimethylhydrazine group showed that it caused neoplastic changes with cytogenetic abnormality identified by hematoxylin and eosin staining and G-banding analysis, respectively. Such changes were similar to those seen in human sporadic colorectal carcinogenesis. Key words: Rectal cancer, diallyl disulfide, dimethyl hydrazine, chromosomal aberrations, intrachromosomal instability, mitotic index.

Early Histopathological Changes in New-Onset Diabetes After Kidney Transplantation

BackgroundNew-onset diabetes after transplantation (NODAT) is one of the most common complications after kidney transplantation. MethodsPatients were randomly assigned to receive cyclosporine A–based or tacrolimus-based immunosuppression. Fasting and oral glucose tolerance tests were performed, and the patients were assigned to one of the following 3 groups, on the basis of the results: normal, impaired fasting glucose/impaired glucose tolerance, or NODAT. NODAT developed in 14% of patients receiving cyclosporine A–based immunosuppression and in 26% of patients taking tacrolimus (P = .0002). ResultsAlbumin levels were similar, but uric acid level (P = .002) and the age of the recipient (P = .003) were significantly different between the diabetic and the normal groups. Evaluation of tissue samples revealed that acute cellular rejection and interstitial fibrosis/tubular atrophy were significantly different in the NODAT group. Changes in the Banff score provided significant difference regarding tubulitis and interstitial inflammation (P = .05). ConclusionsThe pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier, before the development of any sign of functional impairment.

Liver Biopsy and FibroScan to Detect Early Histopathological Changes in Chronic HBV Patients Not Candidate for Treatment.

BackgroundWe aimed at evaluating liver biopsy and FibroScan (FS) to assess early histopathological changes among chronic hepatitis B virus (HBV) patients not candidates for treatment.MethodsOne hundred thirty-five chronic hepatitis B naive patients were followed up twice weekly at National Hepatology and Tropical Medicine Research Institute. All patients were not candidates for treatment according to both Egyptian and international guidelines. Pre-enrollment assessment was performed through biochemical, serological and quantitative HBV DNA testing. Liver biopsy was performed to 59 patients based on the guidelines while FS was performed to patients who were not candidates for liver biopsy (102 patients). Twenty-six patients performed both liver biopsy and FS (isolated liver biopsy 33 patients and isolated FS 76 patients).ResultsAt the end of study period, liver biopsy group showed that majority of subjects had grade F1 fibrosis (61.0%). Only 13.6% were F3. FS showed that almost half (47.1%) of subjects had a grade of F0 and 21.6% with grade F1. Only 4.9% of subjects had fibrosis grades of F3 or F4. In each test, nearly two-thirds of patients had evidence of F0/F1 fibrosis and the remaining one-third had more marked fibrosis. The degree of fibrosis as detected by both liver biopsy and FS was directly related to alanine aminotransferase (ALT), aspartate aminotransferase (AST), S. albumin and prothrombin. Patients with advanced fibrosis had significantly higher ALT and AST, while their S. albumin and prothrombin were significantly lower than those with minimal fibrosis.ConclusionFS study requires further validation in HBV but could be confidently used at the present time as a predictor for the degree of hepatic fibrosis in chronic HBV patients. Liver biopsy could be spared for cases that present with elevated liver functions and/or marked impairment of synthetic liver functions.

Early histopathologic changes in the retina and optic nerve in canine primary angle‐closure glaucoma

To characterize the morphology of canine globes enucleated 1-5days after the onset of overt clinical disease recognized by the owner. Paraffin-embedded globes from 47 dogs with acute primary angle-closure glaucoma (PACG) and 10 control dogs free of ocular disease were sectioned in the vertical plane sampling the optic nerve. Hematoxylin and eosin (H&E)-stained sections were used to count ganglion cell numbers. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify cell death, and MHCII immunohistochemistry was used to evaluate for antigen-presenting phagocytes in a smaller subset of cases. MHCII-labeled phagocytes were present in the optic nerve and retina within the first 24h of documented glaucoma suggesting an early up-regulation. Globes removed within 1day of overt clinical disease had a mild neutrophilic infiltrate in the retina and optic nerve as well as marked ganglion cell necrosis. By 5days after clinical signs appear, there is a rapid decline in the number of ganglion cells and cell death detected by TUNEL labeling in the outer and inner nuclear layers of the retina, but not the ganglion cell layer. The neuropil of the optic nerve progresses from edema and neutrophilia to malacia. These findings suggest that retinal and optic nerve degeneration in dogs with PACG progresses rapidly to irreversible tissue loss within days of recognizable clinical disease.

Time course of early histopathological lung changes in an ovine model of acute lung injury and pulmonary infection

ABSTRACTLarge animal models are valuable tools in biological and medical lung research. Despite the existence of established large animal models, the scientific progress requires more detailed description and expansion of established methods. Previously, we established an ovine model of acute lung injury and subsequent bacterial instillation into the lungs. The current study was designed to assess the time course of early lung histopathological alterations in a large animal model. Injury was induced by smoke inhalation and instillation of live Pseudomonas aeruginosa into the lungs. After 4, 8, 12, 18, and 24 hours, respectively, lung tissue was harvested and histopathological changes were evaluated (n = 4 each). Additional four sheep received no injury and only lung tissue was taken. In injured animals, bronchial obstruction score increased over time and was significantly elevated from 12 to 24 hours (P < .05 versus no injury). Inflammation score was significantly increased at 12 and 18 hours (P < .05 versus no injury). Hemorrhage score was increased at 8 and 12 hours (P < .05 versus no injury). Alveolar edema score was significantly higher in injured sheep at 8, 18, and 24 hours (P < .05 each versus no injury). In conclusion, bronchial obstruction and alveolar edema scores significantly increased over time and reached a plateau, while both inflammation and hemorrhage scores were transiently increased peaking around the 12-hour time point. This information improves the understanding of lung histopathological alterations following acute lung injury and pulmonary infection and may help optimizing the timing of study interventions and evaluation time points in future experiments with this model.

The expression of α-smooth muscle actin during the lung injury induced by hyperoxia

To explore the expression of α-smooth muscle actin (α-SMA) during the lung injury induced by hyperoxia in infantile rats. Sixty-four male Sprague-Dawley (SD) rats about 3 weeks were randomly assigned into normal control group which exposured to room air [fraction of inspired oxygen (FiO(2)) was 0.21] and hyperoxia exposure group (95%O(2)) according to random digits table. Eight rats in each group were randomly sacrificed at day 1, 7, 14 and 21.Pulmonary tissue remodeling was observed by hematoxylin-eosin (HE) staining. Immunohistochemistry method was performed to evaluate the expression of α-SMA in pulmonary tissue, further Western blotting was also made to determine the expression of α-SMA. The early histopathologic changes after HE were inflammation and edema in pulmonary tissue, while the later changes were interstitial hyperplasia and fibroblast proliferation. The expression of α-SMA was very slight in bronchial epithelium, alveolar epithelium and alveolar interstitium in normal control group, but increased with the time of hyperoxia exposure prolonged and peaked at 21st day. Western blotting detected that the expression of α-SMA after hyperoxia exposure for 1 day and 7 days in hyperoxia exposure group presented no difference compared with normal control group (1.02±0.12 vs. 1.00±0.13, 1.05±0.14 vs. 0.99±0.12, both P>0.05), but the expression of α-SMA after hyperoxia exposure for 14 days and 21 days was increased compared with normal control group (1.27±0.21 vs. 1.05±0.15, 2.26±0.28 vs. 1.05±0.14, P<0.05 and P<0.01). Pulmonary fibrosis remodeling was caused by hyperoxia exposure. The expression of α-SMA in pulmonary tissue in hyperoxia exposure groups obviously increased, and could play an important role in pulmonary fibrosis remodeling.

Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma

Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n = 6), Group 2 (ovalbumin induced asthma only, n = 10), Group 3 (ovalbumin induced asthma + MSCs, n = 10), and Group 4 (MSCs only, n = 10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma.

Primary sclerosing cholangitis in children and adolescents: a clinicopathologic study with a proposal of criteria for early diagnosis

INTRODUCTION: Primary sclerosing cholangitis (PSC) has been increasingly diagnosed among children and adolescents due to better recognition of clinical, imaging and pathological features. Thus more patients are diagnosed at a younger age due to imaging and sensitivity optimization. OBJECTIVE: Early liver histopathological (LH) changes are not well described and PSC is not commonly recognized before typical bile duct changes occur on cholangiography (CG). Currently, CG is considered gold standard for adults but nothing is known for early diagnosis in the pediatric age group (0- 20 years old). METHODS: We reviewed clinical history, LH and CG from 47 children and adolescents with PSC (35 males, mean age 13 years old). Forty-three out of 47 patients had been through LH examination from whom 33 had also undergone CG. A clinicopathological correlation was performed. RESULTS: LH showed active neutrophilic cholangitis in 19 patients, moderate neutrophilic pericholangitis in nine, dystrophic changes in the bile duct in eight, and concentric periductal fibrosis in 24 patients. Abnormal CG was found in 24 out of 33 patients and nine had normal results. Eleven out of these 24 patients had abnormal histology before abnormal CG and four patients had abnormal CG before histology. Data of two out of 24 patients were insufficient for correlation and 11 out of 24 had both abnormal liver histology and abnormal imaging findings. CONCLUSION: Our study emphasizes that even when CG is normal, PSC should be exclusively diagnosed by liver biopsy, hence cholangiography being unnecessary. Chronic portal inflammation, neutrophilic pericholangitis, periductal sclerosis and "onion skinning" are characteristic histopathological findings. Neutrophilic pericholangitis may be subtle and easily overlooked in early disease, leading to strong suspicion of PSC.