Fibrosis In Dogs Research Articles

Evaluation of right ventricular diastolic function, systolic function, and circulating galectin-3 concentrations in dogs with pulmonary stenosis.

Cardiovascular diseases with increased right ventricular (RV) afterload induce RV diastolic and systolic dysfunction, and myocardial fibrosis in humans. Studies in dogs with pulmonary stenosis (PS) evaluating RV diastolic function and markers of myocardial fibrosis are lacking. Dogs with PS have echocardiographic evidence of RV diastolic and systolic dysfunction and increased serum concentrations of galectin-3 (Gal-3), a surrogate biomarker for myocardial fibrosis. Forty client-owned dogs (10 controls, 30 with PS). Prospective study. All dogs had systemic blood pressure measurement, serum biochemical analysis, echocardiography, and measurement of serum Gal-3 concentration performed. Variables of RV diastolic function were obtained in 39/40 dogs. Trans-tricuspid flow velocity in early diastole to trans-tricuspid flow velocity in late diastole ratios (RV E/A) were lower (P < .001) in dogs with PS (median, 0.94; range, 0.62-2.04) compared to controls (1.78; 1.17-2.35). Trans-tricuspid flow velocity in early diastole to tricuspid annular myocardial velocity in early diastole ratios (RV E/e') were higher (P < .001) in dogs with PS (11.55; 4.69-28) compared to control (6.21; 5.16-7.21). Variables of RV systolic function were lower in dogs with PS (P = <.001). Serum Gal-3 concentration was higher (P = .002) in dogs with PS (285.1 pg/mL; 94.71-406.97) compared to control dogs (162.83 pg/mL; 52.3-232.82). Dogs with PS have RV diastolic and systolic dysfunction, and increased Gal-3 concentrations. These findings suggest the presence of RV myocardial fibrosis in dogs with PS, which could impact clinical management.

Mechanism of long-term high-dose prednisolone administration producing myocardial fibrosis in beagle dogs.

We previously reported that myocardial fibrosis may be one of the causes of left ventricular hypertrophy and cardiac dysfunction in dogs with hyperglucocorticism (HGC). The detailed mechanism by which myocardial fibrosis of the left ventricle occurs in dogs with HGC remains unclear. Th is study investigated the mechanism by which HGC causes fibrosis of the left ventricle. The impa cts of HGC on the heart by comparing samples obtained from high-dose glucocorticoid (GC)-treated (P) and untreated (C) dogs. The P group included healthy Beagle dogs (n = 6) treated with prednisolone (2 mg/kg, bid, po) for 84 days, and the C group included healthy Beagle dogs (n = 6) euthanized for unrelated reasons. In three of the P group dogs, serum was collected before the start of administration (Day 0) and on Day 84 to measure angiotensin II concentrations and oxidative stress markers (8-hydroxy-2'-deoxyguanosine (8OHdG), NADPH oxidase, and superoxide levels). Samples of the left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), and aortic root were harvested from both groups (n = 6 for each group). Using these tissue samples, angiotensin II type 1 receptor (AT1R), 8OHdG, and transforming growth factor β1 (TGFβ1) immunohistochemical stains were performed. The blood N ADPH oxidase concentration was significantly higher (p = 0.027) in the P group 84 days after initiation of the medication compared to that before prednisolone treatment. By contrast, there was no significant difference in serum angiotensin II (p = 0.450), 8OHdG (p = 0.068), and superoxide (p = 0.057) concentrations. The positive staining rates of AT1R, 8OHdG, and TGFβ1 in the heart (LVFW, RVFW, IVS, and aortic root) were significantly higher in the P group than those in the C group. Angiotensin II and oxidative stress in HGC may cause left ventricular fibrosis in dogs.

Utility of cardiac MRI to diagnose myocardial ischemia and fibrosis in dogs with cardiomegaly secondary to myxomatous mitral valve disease.

To assess whether cardiac MRI or various biomarkers can be used to detect myocardial ischemia and fibrosis in dogs with cardiomegaly secondary to myxomatous mitral valve disease (MMVD). 6 dogs with cardiomegaly secondary to naturally occurring stage B2 MMVD being treated only with pimobendan with or without enalapril and 6 control dogs with no cardiac disease. All dogs were ≥ 5 years old with no systemic illness. Serum cardiac troponin I and concentrations were measured, and dogs were anesthetized for cardiac MRI with ECG-triggered acquisition of native T1- and T2-weighted images. Gadolinium contrast was administered to evaluate myocardial perfusion and late gadolinium enhancement (LGE). Mean T1 and T2 values and regions of LGE were measured with dedicated software. Extracellular volume (ECV) was estimated on the basis of Hct and T1 values of myocardium and surrounding blood. Subjective analysis for myocardial perfusion deficits was performed. Dogs with MMVD had significantly (P = .013) higher cardiac troponin I concentrations than control dogs, but galectin-3 concentrations did not differ (P = .08) between groups. Myocardial fibrosis was detected in 4 dogs with MMVD and 3 control dogs; no dogs had obvious myocardial perfusion deficits. Native T1 and T2 values, postcontrast T1 values, and ECV values were not significantly different between groups (all P > .3). Results suggest that some dogs with cardiomegaly secondary to MMVD may not have clinically relevant myocardial fibrosis.

New surgical model to induce irreversible liver fibrosis by surgical closure of major duodenal orifice in dogs

This study was conducted to induce and evaluate irreversible hepatic fibrosis in dogs by surgical closure of the major duodenal orifice. The study was performed on six healthy local adult dogs. Irreversible hepatic fibrosis was surgically induced in all animals by surgical closure of major duodenal papilla using non-absorbable suture material for 60 days. Induced hepatic fibrosis was evaluated by clinical, ultrasonographical examination, laboratory and histopathological methods. The clinical manifestation of the jaundiced dogs showed reduced food intake, pale-yellowish mucus membrane, inflammatory signs of wound site and severe post-operative pain. Biochemically, there was significant increased values of the aspartate aminotransferase , alkaline phosphatase , alanine aminotransferase , indirect bilirubin, direct bilirubin and total bilirubin especially during first two days after surgery followed by a gradual decrease of these values until the end of the but still higher than normal values. Ultrasonographic examinations showed abnormal change in the liver tissue such as increase in both size and wall thickness of the gall bladder and mottled heterogeneous appearance of the liver during the first two weeks following the surgical induction of the hepatic fibrosis and lasted until the end of the study. Histopathological evaluation of liver samples revealed necrosis of hepatocytes and deposition of eosinophilic material, infiltration of inflammatory cells, recent thrombus in the hepatic vein, fatty change. In conclusion, surgical induction of irreversible hepatic fibrosis in dogs was feasible technique by surgical closure of major duodenal papilla and the results were confirmed by the clinical, ultrasonographical, laboratory and histopathological examination.

Measurement of renal cortical thickness using ultrasound in normal dogs: a reference range study considering bodyweight and body condition score.

The renal cortical thickness (RCT) reflects the pathological condition of the kidney, and measuring this parameter can help diagnose renal fibrosis in dogs. The normal reference range of RCT in dogs is broad (3-8mm) because of the extreme diversity in body size. Therefore, this retrospective, reference interval, and observational design study aimed to establish a normal reference range for RCT in dogs measured using ultrasound by considering bodyweight (BW), body surface area (BSA), body condition score (BCS), and abdominal aorta (Ao) diameter. A total of 60 dogs met the inclusion criteria, and abdominal ultrasound images and medical records of these dogs were analyzed. RCT was measured at 1-3 points where the renal capsule and broad base of the medullary pyramid were clearly observed. Ao diameter was measured caudal to the branch of the left renal artery in the mid-sagittal view. The RCT showed positive correlations with BW and BSA and a negative correlation with BCS, which can be described as follows: RCT (mm)=0.131 × BW - 0.166 × BCS + 3.580. The RCT:Ao ratio was 0.70 ± 0.09 (mean±standard deviation). No significant differences were found in the RCT:Ao ratio depending on BW or BCS. In conclusion, the RCT:Ao ratio and relative RCT considering both BW and BCS are potentially useful for evaluating the normality of the renal cortex on ultrasound examination in dogs with various physiques.

New Surgical Technique to Induce Reversible Liver Fibrosis by Surgical Closure of Major Duodenal Orifice in Dogs

This study was conducted to induce and evaluate reversible liver fibrosis in dogs by surgical closure of the major duodenal orifice. The study was performed on six healthy local adult dogs. Reversible liver fibrosis was surgically induced in all animals by surgical closure of major duodenal papilla using absorbable suture material for 60 days. Induced liver fibrosis was assessed by clinical, ultrasonographical examination, laboratory and histological methods. The clinical manifestation of the jaundiced dogs showed reduced food intake, pale-yellowish mucus membrane, inflammatory signs of the wound site and severe postoperative pain. Biochemically, there was significantly increased values of the aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, indirect bilirubin, direct bilirubin and total bilirubin especially during the first two days after surgery followed by a gradual decrease of these values until the end of the but still higher than normal values. Ultrasonographic examinations showed abnormal changes in the liver tissue such as an increase in both size and wall thickness of the gall bladder and mottled heterogeneous appearance of the liver during the first two weeks following the surgical induction of the hepatic fibrosis. Histological evaluation of liver samples revealed showed necrosis of hepatocytes and deposition of eosinophilic material, infiltration of inflammatory cells, recent thrombus in the hepatic vein, fatty change. Slight clinical, biochemical, ultrasonographic improvement was observed at 30th post-operative day. In conclusion, surgical induction of reversible liver fibrosis in dogs was an easy technique by surgical closure of major duodenal papilla and the results were confirmed by the clinical, ultrasonographical, laboratory and histological examination.

Usefulness of noninvasive shear wave elastography for the assessment of hepatic fibrosis in dogs with hepatic disease.

BackgroundTwo‐dimensional shear wave elastography (2D‐SWE) can noninvasively evaluate hepatic elastic modulus as shear wave velocity (SWV). Additionally, it may predict the presence of clinical relevant hepatic fibrosis (≥F2) in dogs with hepatic disease.ObjectivesTo investigate whether SWV measured by 2D‐SWE can differentiate between dogs with (≥F2) and without (F0‐1) clinically relevant hepatic fibrosis.AnimalsTwenty‐eight client‐owned dogs with hepatic disease and 8 normal healthy Beagle dogs were enrolled.MethodsIn this cross‐sectional prospective study, SWVs were measured using 2D‐SWE in all dogs. Hepatic fibrosis stages and necroinflammatory activity grades were histopathologically evaluated using a histological scoring scheme that was adapted from the Ishak schema used in human medicine.ResultsMedian SWVs were significantly higher in dogs with clinically relevant hepatic fibrosis (2.04 m/s; range, 1.81‐2.26 m/s) than in healthy dogs (1.51 m/s; range, 1.44‐1.66 m/s; P = .007), and dogs without clinically relevant hepatic fibrosis (1.56 m/s; range, 1.37‐1.67 m/s; P < .001). However, no significant difference was found in the SWVs between dogs without clinically relevant hepatic fibrosis and healthy dogs (P = .99). Furthermore, median SWVs were not significantly different among dogs with necroinflammatory activity, those without necroinflammatory activity, and healthy dogs (Kruskal‐Wallis test, P = .12).Conclusions and Clinical ImportanceThe 2D‐SWE may be useful for predicting the presence of hepatic fibrosis in dogs with hepatic disease.

Clinical trial of adjunctive autologous platelet-rich plasma treatment following diamond-burr debridement for spontaneous chronic corneal epithelial defects in dogs.

OBJECTIVE To evaluate the effects of adjunctive treatment with autologous platelet-rich plasma (PRP) on corneal reepithelialization, vascularization, and fibrosis in dogs with spontaneous chronic corneal epithelial defects (SCCEDs). DESIGN Randomized, controlled, double-masked clinical trial. ANIMALS 40 client-owned dogs with uncomplicated SCCEDs. PROCEDURES All dogs were treated with diamond-burr epithelial debridement (DBD) of affected eyes, topical tobramycin solution and atropine sulfate ointment application, and Elizabethan collar placement for 4 weeks. Dogs were randomly assigned to topical ocular administration of autologous PRP (n = 20) or artificial tear solution (control group; 20) 4 times daily for 28 days. Recheck examinations were performed approximately 2 and 4 weeks after treatment began to evaluate SCCEDs for corneal reepithelialization, and semiquantitative corneal vascularization and corneal fibrosis scores were assigned according to affected corneal surface area. Results were compared between groups. RESULTS All dogs completed the study. The SCCEDs had completely reepithelialized in 11 (55%) control dogs and 12 (60%) PRP-treated dogs by the 2-week reevaluation, and in 15 (75%) control dogs and 18 (90%) PRP-treated dogs by the 4-week reevaluation. No significant differences were identified between groups in these proportions nor in mean differences from pretreatment scores for corneal vascularization and fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE In this preliminary study involving dogs with uncomplicated SCCEDs, topical PRP administered as an adjunctive treatment following DBD had no significant effect on healing. A larger study is warranted to support or refute these findings and to determine the effects of adjunctive PRP treatment for dogs with complicated SCCEDs.

A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs.

Ciliopathies presenting as inherited hepatorenal fibrocystic disorders are rare in humans and in dogs. We describe here a novel lethal ciliopathy in Norwich Terrier puppies that was diagnosed at necropsy and characterized as diffuse cystic renal disease and hepatic fibrosis. The histopathological findings were typical for cystic renal dysplasia in which the cysts were located in the straight portion of the proximal tubule, and thin descending and ascending limbs of Henle’s loop. The pedigree of the affected puppies was suggestive of an autosomal recessive inheritance and therefore, whole exome sequencing and homozygosity mapping were used for identification of the causative variant. The analyses revealed a case-specific homozygous splice donor site variant in a cilia related gene, INPP5E: c.1572+5G>A. Association of the variant with the defect was validated in a large cohort of Norwich Terriers with 3 cases and 480 controls, the carrier frequency being 6%. We observed that the identified variant introduces a novel splice site in INPP5E causing a frameshift and formation of a premature stop codon. In conclusion, our results suggest that the INPP5E: c.1572+5G>A variant is causal for the ciliopathy in Norwich Terriers. Therefore, genetic testing can be carried out in the future for the eradication of the disease from the breed.

Hepatic Fibrosis in Dogs.

Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic hepatitis (CH). The development of fibrosis is a crucial event in the progression of hepatic disease that is of prognostic value. The pathophysiology of hepatic fibrosis in human patients and rodent models has been studied extensively. Although less is known about this process in dogs, evidence suggests that fibrogenic mechanisms are similar between species and that activation of hepatic stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs requires histopathological examination of a liver biopsy specimen. However, performing a liver biopsy is invasive and assessment of fibrotic stage is complicated by the absence of a universally accepted staging scheme in veterinary medicine. Serum biomarkers that can discriminate among different fibrosis stages are used in human patients, but such markers must be more completely evaluated in dogs before clinical use. When successful treatment of its underlying cause is feasible, reversal of hepatic fibrosis has been shown to be possible in rodent models and human patients. Reversal of fibrosis has not been well documented in dogs, but successful treatment of CH is possible. In human medicine, better understanding of the pathomechanisms of hepatic fibrosis is leading to the development of novel treatment strategies. In time, these may be applied to dogs. This article comparatively reviews the pathogenesis of hepatic fibrosis, its diagnosis, and its treatment in dogs.

Shunt tube placement for amelioration of cerebrospinal fluid flow obstruction caused by spinal cord subarachnoid fibrosis in dogs.

To describe a novel technique for ameliorating cerebrospinal fluid flow obstruction secondary to pia-arachnoid fibrosis in dogs and report outcome. Descriptive report and retrospective case series. Dogs with cerebrospinal fluid (CSF) flow obstruction (n = 7). Medical records were searched for dogs that had a subarachnoid-subarachnoid shunt placed for treatment of CSF flow obstruction. Data collected included age, sex, breed, clinical signs and duration of signs prior to examination, neurologic status and localization prior to surgery, pre-surgical diagnostics, surgical technique, histopathology, postoperative neurologic examination, time to discharge from hospital, and outcome. All dogs were diagnosed at surgery with a fibrotic adhesion between the arachnoid and pia mater. A subarachnoid shunting tube was implanted to allow CSF flow across the lesion site. Five dogs showed improvement of clinical signs, 3 of which showed complete recovery and 2 of which showed improvement without resolution of all clinical signs. Two dogs showed no change at 7 and 24 months postoperatively. Bridging a region of pia-arachnoid fibrosis with a tube placed in the subarachnoid space can ameliorate or prevent progression of associated clinical signs.

Immunophenotypical analysis of pancreatic interstitial cells in the developing rat pancreas and myofibroblasts in the fibrotic pancreas in dogs and cats.

Pancreatic fibrosis develops as the results of the activity of myofibroblasts capable of producing collagens. The myofibroblasts derive from pancreatic interstitial cells, including pancreatic stellate cells (PSCs), which can express glial fibrillary acidic protein (GFAP). First, we investigated the expression patterns of vimentin, desmin, α-smooth muscle actin (α-SMA), Thy-1 and GFAP in the developing rat pancreas (in fetuses at 18 and 20 days, neonates from 1 to 21 days, and adults). Interstitial cells in the developing pancreas expressed vimentin, desmin, GFAP and Thy-1 at varying degrees; interestingly, the reactivity for desmin and vimentin was the highest in fetuses. GFAP expression was consistent between fetuses and neonates, and Thy-1 reactivity transiently increased after birth; however, α-SMA-positive interstitial cells were rarely seen. Next, we analyzed the immunophenotypical characteristics of myofibroblasts appearing in pancreatic fibrosis in dogs and cats. With increasing fibrotic grade, myofibroblasts showed increased expression of vimentin, desmin and α-SMA, in addition to increased GFAP expression. Collectively, pancreatic interstitial cells and myofibroblasts may have similar immunophenotypes, and myofibroblasts might originate partly from GFAP-expressing PSCs.

7S Fragment of Type IV Collagen as a Serum Marker of Canine Liver Fibrosis.

The aim of this study was to assess whether the serum levels of the 7S fragment of type IV collagen may aid in diagnosing liver fibrosis in dogs. The study was carried out on 20 dogs with liver disease. Serum levels of the 7S fragment of type IV collagen were measured in all dogs. The analysis showed that healthy dogs and dogs with type 1, 2 and 3 liver fibrosis had low serum concentrations of the 7S fragment of type IV collagen compared to dogs with type 4 liver fibrosis. The study revealed that the assessment of serum levels of the 7S fragment of type IV collagen is useful in the diagnosis of advanced liver fibrosis and cirrhosis.

Cytologic features of hepatic fibrosis in dogs: a retrospective study on 22 cases.

Liver cytology has diagnostic value for the identification of neoplastic and nonneoplastic hepatic diseases. However, so far the diagnosis of fibrotic changes has traditionally been restricted to histopathology. The aim of this study was to describe the cytologic features that may help in the recognition of hepatic fibrosis. Cytologic smears from the liver of dogs histologically diagnosed with hepatic fibrosis (Group A) were selected and compared to liver smears from dogs without hepatic fibrosis (Group B). A differential count of hepatocytes, spindle cells, mast cells, granulocytes, lymphocytes/plasma cells, and macrophages was documented for each case, and means for the fibrosis and nonfibrosis group were compared. The relative and total numbers of spindle cells and mast cells were significantly higher in the fibrosis group than in the nonfibrosis group. The optimal cutoff point for the spindle cells to hepatocytes ratio was 0.107 (ie, one spindle cell per 10 hepatocytes), with 95.5% sensitivity and 100% specificity for the cytologic diagnosis of hepatic fibrosis. The optimal cutoff point for the ratio mast cells to hepatocytes was 0.04 (ie, 4 mast cells per 100 hepatocytes) with 86.4% sensitivity and 90% specificity. The presence of relatively and absolutely increased numbers of spindle and mast cells in hepatic cytology provides a rational basis to identify fibrosis of hepatic parenchyma. Based on a reasonable sensitivity and specificity, the cytologic diagnosis of hepatic fibrosis seems feasible.

Development of a novel in vivo corneal fibrosis model in the dog

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading scale, modified McDonald-Shadduck (mMS) scoring system, optical coherence tomography (OCT), corneal histopathology, immunohistochemistry (IHC), and transmission electron microscopy (TEM). The used alkali burn dose to produce corneal fibrosis was well tolerated as no significant difference in mMS scores between control and treatment groups (p = 0.89) were detected. The corneas of alkali burned dogs showed significantly greater levels of α-smooth muscle actin, the fibrotic marker, than the controls (p = 0.018). Total corneal thickness of all dogs post-burn was significantly greater than baseline OCT images irrespective of treatment (p = 0.004); TEM showed that alkali burned corneas had significantly greater minimum and maximum interfibrillar distances than the controls (p = 0.026, p = 0.018). The tested topical corneal alkali burn dose generated significant opacity and fibrosis in dog corneas without damaging the limbus as evidenced by histopathology, IHC, TEM, and OCT findings, and represents a viable large animal corneal fibrosis in vivo model. Additional in vivo SAHA dosing studies with larger sample size are warranted.

The TcI and TcII Trypanosoma cruzi experimental infections induce distinct immune responses and cardiac fibrosis in dogs.

Trypanosoma cruzi infection may be caused by different strains with distinct discrete typing units (DTUs) that can result in variable clinical forms of chronic Chagas disease. The present study evaluates the immune response and cardiac lesions in dogs experimentally infected with different T. cruzi strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII DTU, respectively. During infection with the Col strain, increased levels of alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4. The latter suggests that during the acute phase, infection with the Col strain may remain unnoticed by circulating mononuclear cells. In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium. Conversely, infection with the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of CD4+/CD8+ T-lymphocytes and alterations in monocyte number. The Y strain stimulated the production of interferon-γ by CD4+ and CD8+ T-lymphocytes and IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

Transforming growth factor beta 1 activation, storage, and signaling pathways in idiopathic pulmonary fibrosis in dogs.

BackgroundThe pathogenesis of idiopathic pulmonary fibrosis (IPF) in dogs is poorly understood. In human, transforming growth factor β1 (TGF‐β1) is considered central in the pathogenesis.ObjectivesTo investigate TGF‐β1 pathway in IPF.AnimalsLung tissues from 12 affected and 11 control dogs. Serum from 16 affected West Highland white Terriers (WHWTs) and healthy dogs from predisposed (13 WHWTs, 12 Scottish Terriers and 13 Bichons Frise) and nonpredisposed breeds (10 Whippets, 10 Belgian shepherds, 8 Labradors).MethodsIn this prospective study, immunohistochemistry was used to evaluate expression and localization of TGF‐β1 protein and proteins involved in TGF‐β1 signaling (TGF‐β receptor type I and phospho‐Smad2/3). Pulmonary expression of TGF‐β1 and molecules involved in its storage (latent TGF‐β binding proteins [LTBP] 1, 2, and 4), activation (ανβ6 and ανβ8 integrins, thrombospondin‐1) and signal inhibition (Smad 7) was analyzed by quantitative reverse transcriptase PCR. Circulating TGF‐β1 concentration was measured by ELISA.ResultsIn IPF, high level of TGF‐β1 protein was found in areas of fibrosis, epithelial cells had strong expression of TGF‐β receptor type 1 and phospho‐Smad2/3, gene expression was decreased for LTBP 4 (P = .009) and β8 integrin (P < .001) and increased for thrombospondin‐1 (P = .016); no difference was seen for Smad7, LTBP1 and 2. Serum TGF‐β1 concentration was higher in predisposed compared with nonpredisposed breeds (P < .0001).Conclusions and Clinical ImportanceThis study identified an enhanced TGF‐β1 signaling activity in IPF. TGF‐β1 storage and activation proteins with altered expression represent potential therapeutic targets. Higher circulating TGF‐β1 concentration in predisposed breeds might partly explain their susceptibility for IPF.

Associations between N-terminal procollagen type III, fibrosis and echocardiographic indices in dogs that died due to myxomatous mitral valve disease

ObjectivesTo evaluate associations between N-terminal procollagen type III (PIIINP), a serum biomarker of collagen biosynthesis, and myocardial fibrosis in dogs with naturally-occurring myxomatous mitral valve disease (MMVD). AnimalsTwenty-two dogs with echocardiographically-confirmed MMVD were prospectively recruited from a hospital population. All died as a result of MMVD and their hearts were available for post mortem examination. MethodsEchocardiographic measurements and serum PIIINP concentrations were obtained from all dogs prior to death or euthanasia. Serum PIIINP concentrations (μg/mL) were measured using a validated commercially available radioimmunoassay. Myocardial tissue samples were collected post mortem and myocardial fibrosis was scored. The average fibrosis score for all cardiac sites in the heart was designated the global fibrosis score (GFS). The average fibrosis score for all papillary muscle sites was designated the papillary fibrosis score (PFS). Univariate and multivariate linear regression analyses were used separately to evaluate associations between GFS and PFS, respectively, and PIIINP and echocardiographic variables. ResultsLeft ventricular end-diastolic diameter normalized for body weight (LVEDDN) and PIIINP were weakly independently positively associated with both GFS and PFS. LVEDDN and PIIINP were weakly negatively correlated. ConclusionsBoth LVEDDN and serum PIIINP increase with increasing fibrosis score, although these relationships were not strong enough to be clinically useful. Although LVEDDN and PIIINP were positively correlated with fibrosis, PIIINP decreased with increasing LVEDDN, suggesting a complex interplay between fibrosis and remodeling in MMVD.

Morphological and electron microscopic effects of mitomycin C inhalation in experimentally induced laryngeal fibrosis in dogs

Abstract This study was carried out to investigate the morphological and ultrastructural effects of mitomycin C in the inhalational form on induced laryngeal tissue injuries and fibrosis. This study was carried out on 17 cross-breed clinically healthy dogs. Three dogs were included in a normal control group. The rest of the 14 dogs were subjected to induction of laryngeal fibrosis and assigned randomly to two equal groups: one treated with inhalational mitomycin C and the other was an untreated control group. Tissue biopsies were studied after HE it was markedly reduced in the treated group. The untreated group showed extensive well-organized fibrosis that was significantly increased compared with the other groups. Results were confirmed by electron microscopy. Inhalation of mitomycin C has a potent antifibrotic effect through decreasing the activity of fibroblast evident by the decrease in both the size of fibroblast and the density of the intrafibroblast endoplasmic reticulum.

Early low-frequency stimulation of the pudendal nerve can inhibit detrusor overactivity and delay progress of bladder fibrosis in dogs with spinal cord injuries

To determine the inhibitory effects of pudendal nerve stimulation (5 Hz) on bladder overactivity at the early stage of spinal cord injury (SCI) in dogs, and to explore the possible effects on delayed progression of bladder fibrosis after SCI. The study was performed using six dogs with spinal cord transection at the T9–T10 level. Group 1 (three dogs) under went low-frequency electrical stimulation of the pudendal nerve 1 day after spinal cord transection. Group 2 (three dogs) underwent only spinal cord transection. All dogs underwent urodynamic examination at 1 and 3 months after SCI. The bladders were removed for histological examination of fibrosis at 3 months after SCI. Bladder capacity and compliance were significantly increased (P<0.05) by pudendal nerve stimulation in group 1 when compared with group 2 at 1 and 3 months after SCI. Non-voiding contractions (NVCs) were inhibited in group 1 compared with group 2. Collagen fibers were significantly increased and elastic fibers were significantly decreased (P<0.05) in group 2 when compared with group 1. Early low-frequency pudendal nerve stimulation can inhibit detrusor overactivity (DO), increase bladder capacity and delay the progression of bladder fibrosis.