Degenerative Morphological Changes Research Articles

Evaluation of the inhibitory effects of sitamaquine on Babesia infections

The treatment strategies for either human or animal babesiosis have been established and used for many years. With the rising indications of drug resistance and adverse side effects, finding effective and alternative therapies is urgently needed. Sitamaquine (SQ) is an 8-aminoquinoline that was first synthesized as a part of the collaborative anti-malarial program that led to primaquine. In this study, we evaluated the inhibitory effects of SQ on Babesia spp. in vitro and in vivo. The half-maximal inhibitory concentration (IC50) on in vitro cultured Babesia gibsoni was 8.04 ± 1.34 μM. Babesia gibsoni parasites showed degenerative morphological changes following SQ treatment. The in vivo growth inhibitory effects of SQ were evaluated in BALB/c mice infected with B. microti and atovaquone (ATV)-resistant B. microti strain. Oral administration of SQ at a dose of 20 mg/kg significantly inhibited the growth of B. microti and ATV-resistant B. microti. Meanwhile, SQ also showed inhibitory effects on the growth of B. rodhaini, a lethal rodent Babesia species. All mice infected with B. rodhaini treated with SQ survived, whereas the mice in the control group succumbed to the disease. The results obtained in this study indicate that SQ has potent inhibition effects against Babesia spp., which support SQ as a prospective alternative candidate for babesiosis treatment.

Plasticity changes in neuromuscular junction morphology and related regulatory proteins in the hibernating ground squirrel.

Skeletal muscle disuse atrophy can cause degenerative changes in neuromuscular junction morphology. Although Daurian ground squirrels (Spermophilus dauricus) are a natural anti-disuse animal model for studying muscle atrophy during hibernation, little is known about the morphological and regulatory mechanisms of their neuromuscular junctions. Here, we found that morphological indices of the soleus muscle were significantly lower during hibernation (torpor and interbout arousal) compared to pre-hibernation but recovered during post-hibernation. In the extensor digitorum longus muscle, neuromuscular junction morphology did not change significantly during hibernation. Agrin-Lrp4-MuSK is a key pathway for the formation and maintenance of the neuromuscular junction. Our results showed that low-density lipoprotein receptor-associated protein 4 (Lrp4) expression in the soleus (slow muscle) decreased by 46.2% in the interbout arousal group compared with the pre-hibernation group (p = 0.019), with recovery in the post-hibernation group. Compared to the pre-hibernation group, agrin expression in the extensor digitorum longus (fast muscle) increased by 67.0% in the interbout arousal group (p = 0.016). In conclusion, periodic up-regulation in agrin expression during interbout arousal may be involved in the maintenance of neuromuscular junction morphology in the extensor digitorum longus muscle during hibernation. The degenerative changes in neuromuscular junction morphology and the periodic decrease in Lrp4 protein expression in the soleus during hibernation, these changes recovered to the pre-hibernation levels in the post-hibernation group, also exhibiting significant plasticity. This plasticity may be an important mechanism for resisting disuse atrophy in hibernating animals.

Agent Orange Causes Metabolic Dysfunction and Molecular Pathology Reminiscent of Alzheimer's Disease.

Agent Orange, an herbicide used during the Vietnam War, contains 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Agent Orange has teratogenic and carcinogenic effects, and population-based studies suggest Agent Orange exposures lead to higher rates of toxic and degenerative pathologies in the peripheral and central nervous system (CNS). This study examines the potential contribution of Agent Orange exposures to neurodegeneration. Human CNS-derived neuroepithelial cells (PNET2) treated with 2,4-D and 2,4,5-T were evaluated for viability, mitochondrial function, and Alzheimer's disease (AD)-related proteins. Treatment with 250μg/ml 2,4-D or 2,4,5-T significantly impaired mitochondrial function, caused degenerative morphological changes, and reduced viability in PNET2 cells. Correspondingly, glyceraldehyde-3-phosphate dehydrogenase expression which is insulin-regulated and marks the integrity of carbohydrate metabolism, was significantly inhibited while 4-hydroxy-2-nonenal, a marker of lipid peroxidation, was increased. Tau neuronal cytoskeletal protein was significantly reduced by 2,4,5-T, and relative tau phosphorylation was progressively elevated by 2,4,5-T followed by 2,4-D treatment relative to control. Amyloid-β protein precursor (AβPP) was increased by 2,4,5-T and 2,4-D, and 2,4,5-T caused a statistical trend (0.05 < p<0.10) increase in Aβ. Finally, altered cholinergic function due to 2,4,5-T and 2,4-D exposures was marked by significantly increased choline acetyltransferase and decreased acetylcholinesterase expression, corresponding with responses in early-stage AD. Exposures to Agent Orange herbicidal chemicals rapidly damage CNS neurons, initiating a path toward AD-type neurodegeneration. Additional research is needed to understand the permanency of these neuropathologic processes and the added risks of developing AD in Agent Orange-exposed aging Vietnam Veterans.

Influence of doxorubicin on the extracellular matrix of the liver of rats under conditions of chronic alcoholic hepatitis

The liver has a high regenerative potential that is dependent on many factors, in particular adenosine monophosphate kinase signaling, however, long-term alteration, such as daily alcohol consumption, turns regeneration into a chronic disease such as fibrosis, the end stage of which is cirrhosis. Hepatic extracellular matrix proteins are important triggers of enhanced stellate cell function during the progression of liver fibrosis. The experiments were performed on Wistar rats divided into four groups: control group; doxorubicin injection group (1.25 mg/kg); chronic alcohol hepatitis group; injection of doxorubicin during alcoholic hepatitis group, where we studied the total concentration of glycosaminoglycans, concentration of heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, free oxyproline and sialic acids in the liver tissue homogenate. Cells with Mallory-Denk bodies were present in the liver of rats from the alcohol hepatitis group, which consisted of tangled balls of intermediate filaments and showed eosinophilia in the cytoplasm of degenerative hepatocytes. There were also necrotic changes in cells. Sinusoidal capillaries were locally dilated. In the central sections of the liver lobules of rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the central veins were expanded, their endothelium was thinned. Sinusoidal capillaries were locally expanded, there were no blood cells in their lumens. The nuclei of the vast majority of hepatocytes were in a state of karyopyknosis, karyorrhexis, and karyolysis. Mallory-Denk bodies were present in the cytoplasm of cells. Administration of doxorubicin to animals with chronic alcoholic hepatitis leads to an increase in the total concentration of glycosaminoglycans, the concentration of chondroitin sulfates, a decrease in the heparin-heparan fraction of glycosaminoglycans and no changes in concentration of the keratan-dermatan fraction in the liver of rats compared to the control group. In the group of rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the concentrations of total glycosaminoglycans, heparin-heparan fraction, and chondroitin fraction significantly increased, and the content of the keratan-dermatan fraction of glycosaminoglycans significantly decreased compared to animals with chronic alcoholic hepatitis. In rats injected with doxorubicin against the background of chronic alcoholic hepatitis, the content of free oxyproline decreased by 1.25 times, sialic acids – by 1.36 times, compared to the group of animals with chronic alcoholic hepatitis. Administration of ethanol or doxorubicin in combination with ethanol to rats causes morphological changes in the liver that are characteristic of chronic alcoholic hepatitis. Administration of doxorubicin to rats leads to degenerative morphological changes in the liver lobules. The administration of doxorubicin prevents alcohol-induced collagenolysis and the breakdown of glycoproteins, but increases the breakdown of proteoglycans due to an increase in the content of chondroitin and heparin-heparan fractions.

Basal Blood Morphology, Serum Biochemistry, and the Liver and Muscle Structure of Weaned Wistar Rats Prenatally Exposed to Fumonisins.

Simple SummaryCereal, which is the main ingredient of animal feed, is often contaminated with mold, which produces heat-resistant, carcinogenic, and harmful metabolites/toxins called fumonisins. Feed contamination with fumonisins is a worldwide problem; however, the dietary intake of fumonisins is difficult to estimate because their concentrations in many products are unknown. The effects of consuming fumonisin-contaminated feed on animal health are not fully known, and the economic losses that are related to health care or animal husbandry are difficult to calculate as fumonisins are found commonly in foods, including those that are intended for infants or pregnant dams. The involuntary intake of moldy feed leads to a serious health risk with long-term effects. The research on prenatal exposure to fumonisins is limited. Previous studies have shown that prenatal fumonisins exposure causes abnormalities in the bone and enteric nervous system development. Therefore, it is very important to study the effects of prenatal exposure to fumonisins on the general development of offspring at different periods of life, including weaning.Cereals are often contaminated with fumonisins, which are the toxic byproducts of mold. The aim of the study was to determine the effect of maternal exposure to fumonisins on the development and the liver function of the offspring at weaning. Two doses of fumonisins (60 and 90 mg/kg b.w.) were tested. The changes in the basal blood morphology, the biochemical parameters, the absolute and relative weights of the vital organs, and the changes in the cardiac and biceps brachii muscle histology were studied. The liver damage was assessed by evaluating the liver morphology and the common clinical liver panel. Maternal fumonisin intoxication caused a decrease in the body weight at birth and an increase in the heart, liver, kidney, lungs, ovaries, and testes weights. The cytokines and hormones, as well as the red blood cell counts and hemoglobin levels, were elevated in a dose-dependent manner following the exposure to fumonisins. Maternal exposure caused degenerative morphological and structural changes in the liver, as well as inflammation in the striated muscles, such as the heart and biceps brachii, and disproportionate development of the rat offspring in a dose-dependent manner. Moreover, FB exposure resulted in the disproportional development of the rat offspring in a dose-dependent manner, which was probably caused by the bodily hormonal dysregulation. Prenatal fumonisin exposure can be a pathological precursor for serious diseases, such as obesity and diabetes, later in life.

Association between bone morphology and sagittal disc position in temporomandibular joints of patients with anterior disc displacement.

To analyze the association between sagittal temporomandibular joint (TMJ) disc position of patients with anterior disc displacement evaluated by magnetic resonance imaging (MRI) and bone morphology of the TMJ evaluated by cone-beam computed tomography (CBCT). One hundred and seventy-eight TMJs of 97 patients were retrospectively analyzed. The TMJ disc position was evaluated using MRI and classified into four types: control group (without disc displacement), slight group (disc slightly anteriorly displaced), moderate group (disc moderately anteriorly displaced), and severe group (disc severely anteriorly displaced). The measurements of TMJ bone morphology among four groups were evaluated by CBCT through Mimics software including condyle linear dimensions (condyle length, width, and height), condylar volume and surface area, and the depth and length of the glenoid fossa, joint anterior space, joint superior space, and joint posterior space. The sagittal plane position of the condyle was also assessed. The differences in all the morphologic measurement parameters among the four groups were detected using the one-way analysis of variance or the Kruskal Wallis test, and Chi-square tests. The correlations between disc sagittal position and all the morphologic measurements were also analyzed. There were significant differences in measurements of condyle linear dimensions, condylar volume and surface area, depth of the glenoid fossa, joint spaces, and distribution of the condyle sagittal positions among the four groups. By contrast, there were no statistical differences in terms of the length of the glenoid fossa among the four groups. Correlation analysis revealed that there is a statistically significant negative correlation among condyle linear dimensions, condylar volume and surface area, the depth of the glenoid fossa, joint superior space, and disc position. However, joint posterior space was positively correlated with disc position. A statistically significant correlation was determined between TMJ bone morphology and different sagittal disc positions. Degenerative changes in TMJ bone morphology clinically diagnosed should be altered, which can be the patients' marker of anterior disc displacement.

CT-based evaluation of the acetabulum for age estimation in an Indian population.

Age estimation constitutes an important aspect of forensic research, investigation and human identification. For the purpose of age estimation, various markers within the skeletal framework are employed. Degenerative morphological changes in the skeleton can be used for age estimation in adults. Amongst the various bones, age-progressive changes in the innominate bone are of particular significance in age estimation. Within the pelvis, the acetabulum presents as a durable and well-preserved evidence, characteristic manifestations of which can be employed for age estimation. The present study aimed at a CT-based evaluation of acetabular changes for the purpose of age estimation in an Indian population. CT images of 250 individuals aged 10-88years were scrutinized according to the features defined in the Calce method of acetabular age estimation. Scores were allotted to the various features and a cumulative score was calculated. No significant bilateral and sex differences were observed. Significant correlation was obtained between the scores for these defined characteristics and the chronological age of individuals. Population-specific regression models were generated for age estimation. The scoring method devised in the present research requires further validation as it represents a new tool for age estimation in medico-legal cases.

“Histological and ultrastructural changes of white blood cells in vitro storage of human blood at different time intervals”.

Determination of the changes of blood samples is an important subject. The time passing from changing of normal morphology of WBCs to the un-identification period is useful in the determination of the age of in vitro storage blood which in turn helps in determination of post-mortem intervals. This study was done to demonstrate the light microscopic and ultrastructural changes occurring in white blood cells (WBC in vitro samples at different time intervals. Light microscopic examination of blood films using Hematoxylin and Eosin (Hx & E), semithin sections stained with toluidine blue, and electron microscopic examinations were done at intervals of (0, 6, 12, 24, 48, and 60 hours) for in vitro blood samples left at room temperature. Concerning the morphological changes in different WBCs, it was observed that neutrophils had normal structure at zero- and 6-hours post-storage. Degeneration was observed at 12-hours and progressed at 24-, 48-, and 60-hours. Degenerative changes include pyknosis, and irregularity in the nuclear shape, vacuolation, pale-stained, and decreased amount of cytoplasm. At 60 hours most of cells are completely degenerated and cannot be discriminated from other WBCs. Ultrastructurally, it was noticed that the degenerative changes were observed in neutrophils after 12-hours post storage. They progressed gradually at 24-and 48-hours till they became completely unidentifiable at 60hours. Eosinophils showed degenerative changes at 12-, 24-, and 48-hours then they became completely degenerated and un-recognized after 60-hours. In addition, monocytes began to show degenerative morphological changes at 12-, 24-, 48-, and at 60-hours most of them completely degenerated. It was observed that lymphocytes were the most resistant cells as they were the only cells that could be detected at 60-hours by semithin sections. It was concluded that the morphological changes of WBCs of in vitro blood samples could be an indicator of the age of the blood.

Normative Magnetic Resonance Imaging Data of Age-Related Degenerative Changes in Cervical Disc Morphology

Few studies have examined a possible correlation between cervical disc degeneration and disc height. The aim of this study was to establish age-related changes and sex-specific differences of cervical disc height using magnetic resonance imaging (MRI) and to evaluate the relationship between degree of cervical disc degeneration and disc height in asymptomatic subjects. We measured the intervertebral disc anteroposterior diameter and disc height in each disc level using MRI in 1211 relatively healthy volunteers (606 men and 605 women, mean age 49.5 years). We included at least 100 males and 100 females in each decade of life between the 20s and the 70s. Cervical disc degeneration was defined according to the modified Pfirrmann classification system, and disc index and intervertebral disc height narrowing ratio were evaluated on sagittal plane MRI. Intervertebral disc height decreased gradually with increasing age in both sexes. The grade of disc degeneration significantly increased with age in both sexes at every level. Mild disc degeneration was observed even in subjects their 20s. Disc degeneration occurred around the C5-C6 level. The average disc height decreased with aging after the 40s. Disc index and intervertebral disc height narrowing ratio decreased with a progression in the disc degeneration grade in both sexes. This large-scale cross-sectional analysis of cervical spine MRI data in healthy subjects demonstrated that cervical disc height narrowing progresses with age. Cervical disc height narrowing is highly correlated with the progression of disc degeneration.

Extrusions do not affect degenerative morphologic changes in lateral meniscus allografts during midterm follow-ups.

To investigate degenerative morphological changes in meniscus allograft after lateral meniscus allograft transplantation (MAT) based on extrusions. Ninety-one patients who underwent lateral MAT were divided into extruded and non-extruded groups. Serial magnetic resonance imaging scans obtained 6weeks, 1year, and at the last follow-up (midterm, 3-7years) post-surgery were evaluated retrospectively. Degenerative morphological changes at each time point in each group were compared using the postoperative meniscal width, thickness, and intrameniscal signal intensity (IMSI) at the anterior horn, mid-body, and posterior horn. The Lysholm scores and meniscal tears based on graft extrusion were also investigated. The mean age was 33.7 ± 11.1years (64 men and 27 women). Fifty-three (58%) and 38 knees (42%) were classified into the non-extruded and extruded groups, respectively. The overall meniscal width of the mid-body decreased from 9.6 ± 1.3 to 6.5 ± 1.2mm (p < 0.01), and IMSI of mid-body was increased from 1.2 ± 0.1 to 1.7 ± 0.1 (p < 0.01) during midterm follow-ups. No significant differences were observed between the meniscal width, thickness, and IMSI at the anterior horn (n.s.), mid-body (n.s.), and posterior horn (n.s.) of the two groups during the midterm follow-ups. The incidence of meniscus tears and Lysholm scores did not differ significantly between the groups during midterm follow-ups. The overall meniscus width of mid-body decreased while the relative IMSI of mid-body increased during midterm follow-ups after lateral MAT. Meniscal allograft extrusions did not influence postoperative changes in meniscus width, thickness, and relative intrameniscal signal intensity. Level III.

Role of radiologic imaging complex in morpho-pathogenetic approach to sanatorium resort intensity regimen selection in patients with dorsopathies

At the present time for sanatorium treatment of dorsopathies no morpho-pathogenetic principles are based on severity of degenerative spine changes. The choice of treatment modalities is provided according only to clinical signs and the fact of degenerative spine disease presence, in spite of limitations and contradictions to some resort procedures because of their mechanisms and peculiarities of therapeutic effects. Materials and methods. Comparison of complex imaging examination and sanatorium resort intensity regimen medical appointments of 952 patients with dorsopathies was provided depending on morphological pattern and severity of degenerative spine changes. Case histories, sanatorium medical outpatient cards and the results of radiologic imaging (computed tomography, magnetic resonance imaging, spondylography and osteodensitom-etry) were analyzed. Results. Three groups of sanatorium resort therapeutic action intensity (maximal, 376 patients; limited, 493 patients; and minimal, 83 patients) for patients with dorsopathies were established. The most significant morphological criteria of patient distribution into appropriate groups were established, such as bone mineral density state, the presence and severity of spinal osteoarthrosis and spondylolisthesis, vertebral-motor segment stability or instability, vertebral body hemangiomas. The size of intervertebral disc extrusions and grade of disc height decreasing played a secondary role. The value of spondylography, computed tomography, magnetic resonance imaging and dual-energy radioabsorptiometry in determination of these criteria is presented, as far as in imaging algorithm of examination of patients with dorsopathies on the pre-sanatorium stage, with calculation of computed tomography and magnetic resonance imaging sensitivity, specificity and accuracy. Discussion. Forming morpho-pathogenetic approach to sanatorium resort treatment of dorsopathy demands essential application of modern radiologic imaging modalities. The presence, type and severity of degenerative spine morphological changes must be as fundamental as clinical and neurological pattern, affecting sanatorium resort intensity regimen selection and treatment modalities and schemes. In basic cases most advisable radiologic imaging pre-sanatorium examination modality should be computed tomography, but others are also necessary to use when concretely indicated.

In-depth phenotyping reveals common and novel disease symptoms in a hemizygous knock-in mouse model (Mut-ko/ki) of mut-type methylmalonic aciduria

Isolated methylmalonic aciduria (MMAuria) is primarily caused by deficiency of methylmalonyl-CoA mutase (MMUT or MUT). Biochemically, MUT deficiency results in the accumulation of methylmalonic acid (MMA), propionyl-carnitine (C3) and other metabolites. Patients often exhibit lethargy, failure to thrive and metabolic decompensation leading to coma or even death, with kidney and neurological impairment frequently identified in the long-term. Here, we report a hemizygous mouse model which combines a knock-in (ki) missense allele of Mut with a knock-out (ko) allele (Mut-ko/ki mice) that was fed a 51%-protein diet from day 12 of life, constituting a bespoke model of MMAuria. Under this diet, mutant mice developed a pronounced metabolic phenotype characterized by drastically increased blood levels of MMA and C3 compared to their littermate controls (Mut-ki/wt). With this bespoke mouse model, we performed a standardized phenotypic screen to assess the whole-body impairments associated with this strong metabolic condition. We found that Mut-ko/ki mice show common clinical manifestations of MMAuria, including pronounced failure to thrive, indications of mild neurological and kidney dysfunction, and degenerative morphological changes in the liver, along with less well described symptoms such as cardiovascular and hematological abnormalities. The analyses also reveal so far unknown disease characteristics, including low bone mineral density, anxiety-related behaviour and ovarian atrophy. This first phenotypic screening of a MMAuria mouse model confirms its relevance to human disease, reveals new alterations associated with MUT deficiency, and suggests a series of quantifiable readouts that can be used to evaluate potential treatment strategies.

Using PMCT of Individuals of Known Age to Test the Suchey-Brooks Method of Aging in Victoria, Australia.

The estimation of an individual's age at death plays a critical role in the investigation of unidentified human remains. The Suchey-Brooks method, which involves the analysis of degenerative morphological changes in the pubic symphysis, is currently widely used to estimate age in adults. This study tested the applicability of the Suchey-Brooks method on a contemporary adult Australian (Victorian) subpopulation by observing three-dimensional volume-rendered postmortem computed tomographic (PMCT) reconstructions of the pubic symphysis of 204 individuals aged 15-100years. Results showed the method was reliable for females (85% correct allocations) but not for males (67% correct allocations). It is therefore recommended that extreme caution be used when applying the Suchey-Brooks method for estimating age at death of an individual in this subpopulation from PMCT images. The results suggest further investigation into alternate age estimation methods is required.

PARP Inhibitor Protects Against Chronic Hypoxia/Reoxygenation-Induced Retinal Injury by Regulation of MAPKs, HIF1α, Nrf2, and NFκB.

In the eye, chronic hypoxia/reoxygenation (H/R) contributes to the development of a number of ocular disorders. H/R induces the production of reactive oxygen species (ROS), leading to poly(ADP-ribose) polymerase-1 (PARP1) activation that promotes inflammation, cell death, and disease progression. Here, we analyzed the protective effects of the PARP1 inhibitor olaparib in H/R-induced retina injury and investigated the signaling mechanisms involved. A rat retinal H/R model was used to detect histologic and biochemical changes in the retina. H/R induced reductions in the thickness of most retinal layers, which were prevented by olaparib. Furthermore, H/R caused increased levels of Akt and glycogen synthase kinase-3β phosphorylation, which were further increased by olaparib, contributing to retina protection. By contrast, H/R-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinases (MAPK) phosphorylation and activation were reduced by olaparib, via mitogen-activated protein kinase phosphatase 1 (MKP-1) expression. In addition, H/R-induced hypoxia-inducible factor 1α (HIF1α) levels were decreased by olaparib, which possibly contributed to reduced VEGF expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression was slightly increased by H/R and was further activated by olaparib. Nuclear factor-κB (NFκB) was also activated by H/R through phosphorylation (Ser536) and acetylation (Lys310) of the p65 subunit, although this was significantly reduced by olaparib. Olaparib reduced H/R-induced degenerative changes in retinal morphology. The protective mechanisms of olaparib most probably involved Nrf2 activation and ROS reduction, as well as normalization of HIF1α and related VEGF expression. In addition, olaparib reduced inflammation by NFκB dephosphorylation/inactivation, possibly via the PARP1 inhibition-MKP-1 activation-p38 MAPK inhibition pathway. PARP inhibitors represent potential therapeutics in H/R-induced retinal disease.

The effects of vitamins and selenium mixture or ranitidine against small intestinal injury induced by indomethacin in adult rats.

This study was aimed at investigating morphological and biochemical efficacies of antioxidants on indomethacin-induced small intestinal damage in rats. Group I: control animals (negative control) given only placebo, Group II: (positive control) are animals orally given combination of antioxidants [vitamin C (Vit C), vitamin E (Vit E), β-carotene and sodium selenite (Se)] daily for 3days, Group III: Rats were given only indomethacin, Group IV: animals were given of antioxidants combination for 3days, last dose was given 2hr before the administration of indomethacin. Group V: Animals receiving ranitidine for 3days (second positive control). Group VI: Animals received ranitidine for 3days, last dose was given 2hr before to indomethacin administration. Indomethacin caused degenerative morphological and biochemical changes, which were reversed on antioxidants administration. As a result, we propose that antioxidants combination would be therapeutically beneficial for treating indomethacin-induced lesions of small intestine. PRACTICAL APPLICATIONS: Indomethacin is a widely preferred nonsteroidal anti-inflammatory drug (NSAID) but its side effects on gastrointestinal system are well known. Indomethacin also causes production of reactive oxygen species. Antioxidants and selenium has protective effects. According to the results of this study, antioxidants and selenium can be used as a food supplement for preventing NSAID-induced side effects and toxicity.

Histological characteristics of ovarian follicle atresia in dairy cows with different milk production.

Follicle atresia in mammals is a universal phenomenon characteristic by degenerative morphological changes in granulosa and theca cells. The unfavourable effect of milk production in relation to fertility has been studied starting from the 70s of the last century; however, there is no unambiguous and persuasive data on association of ovarian atresia with milk yield of dairy cows. The aim of this study was to define histological signs of ovarian follicle atresia in dairy cows in relation to their milk production. The ovaries were recovered from slaughtered Holstein dairy cows assigned into two groups according to average level of annual milk production: Group 1 (n=25)-low (≤8,000kg/year) and Group 2 (n=23)-high (≥8,000kg/year). Atresia of antral follicles was evaluated on the basis of histopathological image (staining with basic fuchsine and toluidine blue) of nonovulated follicles, classified into five categories: an initial atresia, cystic atresia, obliterated atresia, atresia with luteinization of the granulosa and follicle structures of the fibrous body-corpus fibrosum. We found that the histopathological image of follicle atresia in groups of low-milk- or high-milk-producing cows is essentially similar. Prevalent form of atresia in follicles of all experimental cows was the formation of fibrous bodies and obliterated atresia. The occurrence of fibrous bodies was significantly higher (55.44%) in low-milk-producing cows compared with high-milk-producing cows (34.61%). In the same way, the higher incidence of obliterated atresia was recorded in ovarian follicles from cows with the lower milk production (36.96%) compared to the cows with the higher milk production (25.48%). In contrast, ovaries from lower milk-producing cows showed lower (p<0.05) incidence of initial (p<0.001) and cystic (p<0.05) follicle atresia than ovaries from the higher milk-producing cows. Our results show that cows in the higher lactation group showed more initial and cystic atresia, what may adversely affect the fertility of dairy cows.

A web-based system for neural network based classification in temporomandibular joint osteoarthritis

ObjectiveThe purpose of this study is to describe the methodological innovations of a web-based system for storage, integration and computation of biomedical data, using a training imaging dataset to remotely compute a deep neural network classifier of temporomandibular joint osteoarthritis (TMJOA). MethodsThis study imaging dataset consisted of three-dimensional (3D) surface meshes of mandibular condyles constructed from cone beam computed tomography (CBCT) scans. The training dataset consisted of 259 condyles, 105 from control subjects and 154 from patients with diagnosis of TMJ OA. For the image analysis classification, 34 right and left condyles from 17 patients (39.9 ± 11.7 years), who experienced signs and symptoms of the disease for less than 5 years, were included as the testing dataset. For the integrative statistical model of clinical, biological and imaging markers, the sample consisted of the same 17 test OA subjects and 17 age and sex matched control subjects (39.4 ± 15.4 years), who did not show any sign or symptom of OA. For these 34 subjects, a standardized clinical questionnaire, blood and saliva samples were also collected. The technological methodologies in this study include a deep neural network classifier of 3D condylar morphology (ShapeVariationAnalyzer, SVA), and a flexible web-based system for data storage, computation and integration (DSCI) of high dimensional imaging, clinical, and biological data. ResultsThe DSCI system trained and tested the neural network, indicating 5 stages of structural degenerative changes in condylar morphology in the TMJ with 91% close agreement between the clinician consensus and the SVA classifier. The DSCI remotely ran with a novel application of a statistical analysis, the Multivariate Functional Shape Data Analysis, that computed high dimensional correlations between shape 3D coordinates, clinical pain levels and levels of biological markers, and then graphically displayed the computation results. ConclusionsThe findings of this study demonstrate a comprehensive phenotypic characterization of TMJ health and disease at clinical, imaging and biological levels, using novel flexible and versatile open-source tools for a web-based system that provides advanced shape statistical analysis and a neural network based classification of temporomandibular joint osteoarthritis.

Chondroitin sulfate and glucosamine sulfate associated to photobiomodulation prevents degenerative morphological changes in an experimental model of osteoarthritis in rats.

The aim of this study was to compare the effects of combined treatment with chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM) on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Forty male Wistar rats were randomly divided into four groups: OA control group (CG); OA animals submitted to PBM treatment (PBM); OA animals submitted to CS/Gl treatment (CS/Gl); OA submitted to CS/GS associated with PBM treatments (GS/Gl + PBM). The CS/Gl started 48h after the surgery, and they were performed for 29 consecutive days. Moreover, PBM was performed after the CS/Gl administration on the left joint. Morphological characteristics and immunoexpression of interleukin 10 (IL-10) and 1 beta (IL-1β) and collagen type II (Col II) of the articular cartilage were evaluated. The results showed that all treated groups (CS/Gl and PBM) presented attenuation signs of degenerative process (measured by histopathological analysis) and lower density chondrocytes [PBM (p = 0.0017); CS/Gl (p = 0.0153) and CS/Gl + PBM (p = 0.002)]. Additionally, CS/Gl [associated (p = 0.0089) or not with PBM (p = 0.0059)] showed significative lower values for OARSI grade evaluation. Furthermore, CS/GS + PBM decreased IL-1β protein expression (p = 0.0359) and increased IL-10 (p = 0.028) and Col II imunoexpression (p = 0.0204) compared to CG. This study showed that CS/Gl associated with PBM was effective in modulating inflammatory process and preventing the articular tissue degradation in the knees OA rats.

Articular cartilage surface roughness as an imaging-based morphological indicator of osteoarthritis: A preliminary investigation of osteoarthritis initiative subjects.

Current imaging-based morphometric indicators of osteoarthritis (OA) using whole-compartment mean cartilage thickness (MCT) and volume changes can be insensitive to mild degenerative changes of articular cartilage (AC) due to areas of adjacent thickening and thinning. The purpose of this preliminary study was to evaluate cartilage thickness-based surface roughness as a morphometric indicator of OA. 3D magnetic resonance imaging (MRI) datasets were collected from osteoarthritis initiative (OAI) subjects with Kellgren-Lawrence (KL) OA grades of 0, 2, and 4 (n = 10/group). Femoral and tibial AC volumes were converted to two-dimensional thickness maps, and MCT, arithmetic surface roughness (Sa ), and anatomically normalized Sa (normSa ) were calculated. Thickness maps enabled visualization of degenerative changes with increasing KL grade, including adjacent thinning and thickening on the femoral condyles. No significant differences were observed in MCT between KL grades. Sa was significantly higher in KL4 compared to KL0 and KL2 in the whole femur (KL0: 0.55 ± 0.10 mm, KL2: 0.53 ± 0.09 mm, KL4: 0.79 ± 0.18 mm), medial femoral condyle (KL0: 0.42 ± 0.07 mm, KL2: 0.48 ± 0.07 mm, KL4: 0.76 ± 0.22 mm), and medial tibial plateau (KL0: 0.42 ± 0.07 mm, KL2: 0.43 ± 0.09 mm, KL4: 0.68 ± 0.27 mm). normSa was significantly higher in KL4 compared to KL0 and KL2 in the whole femur (KL0: 0.22 ± 0.02, KL2: 0.22 ± 0.02, KL4: 0.30 ± 0.03), medial condyle (KL0: 0.17 ± 0.02, KL2: 0.20 ± 0.03, KL4: 0.29 ± 0.06), whole tibia (KL0: 0.34 ± 0.04, KL2: 0.33 ± 0.05, KL4: 0.48 ± 0.11) and medial plateau (KL0: 0.23 ± 0.03, KL2: 0.24 ± 0.04, KL4: 0.40 ± 0.10), and significantly higher in KL2 compared to KL0 in the medial femoral condyle. Surface roughness metrics were sensitive to degenerative morphologic changes, and may be useful in OA characterization and early diagnosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2755-2764, 2017.

28 - Prevalence of degenerative morphological changes in the sacro iliac joint

28 - Prevalence of degenerative morphological changes in the sacro iliac joint