Changes In Muscle Tissue Research Articles

Exenatide improves hepatic steatosis by enhancing lipid use in adipose tissue in nondiabetic rats

To investigate the metabolic changes in skeletal muscle and/or adipose tissue in glucagon-like peptide-1-induced improvement of nonalcoholic fatty liver disease (NAFLD). Male Wistar rats were fed either a control diet (control group) or a high-fat diet (HFD). After 4 wk, the HFD-fed rats were subdivided into two groups; one group was injected with exenatide [HFD-Ex(+) group] and the other with saline [HFD-Ex(-) group] every day for 12 wk. The control group received saline and were fed a control diet. Changes in weight gain, energy intake, and oxygen consumption were analyzed. Glucose tolerance tests were performed after 8 wk of treatment. Histological assessments were performed in liver and adipose tissue. RNA expression levels of lipid metabolism related genes were evaluated in liver, skeletal muscle, and adipose tissue. Exenatide attenuated weight gain [HFD-Ex(-) vs HFD-Ex(+)] and reduced energy intake, which was accompanied by an increase in oxygen consumption and a decrease in the respiratory exchange ratio [HFD-Ex(-) vs HFD-Ex(+)]. However, exenatide did not affect glucose tolerance. Exenatide reduced lipid content in the liver and adipose tissue. Exenatide did not affect the expression of lipid metabolism-related genes in the liver or skeletal muscle. In adipose tissue, exenatide significantly upregulated lipolytic genes, including hormone-sensitive lipase, carnitine palmitoyltransferase-1, long-chain acyl-CoA dehydrogenase, and acyl-CoA oxidase 1 [HFD-Ex(-) vs HFD-Ex(+)]. Exenatide also upregulated catalase and superoxide dismutase 2 [HFD-Ex(-) vs HFD-Ex(+)]. In addition to reducing appetite, enhanced lipid use by exenatide in adipose tissue may reduce hepatic lipid content in NAFLD, most likely by decreasing lipid influx into the liver.

Proteomics of the Dystrophin-glycoprotein Complex and Dystrophinopathy

The largest human gene is represented by the X-chromosomal dystrophin gene of 2.4 million bases, which encodes for the membrane cytoskeletal protein dystrophin. The dystrophin isoform Dp427 has a subsarcolemmal location and forms a supramolecular membrane assembly with a variety of glycoproteins. In healthy muscle fibres, dystrophin acts as an actin-binding protein that links the cytoskeleton via the α/β-dystroglycan complex to the extracellular matrix protein laminin. This trans-sarcolemmal complex is believed to stabilize the muscle surface and thus prevents membrane rupturing during excitation-contraction-relaxation cycles. In the highly progressive muscle wasting disease Duchenne muscular dystrophy, the primary deficiency in dystrophin causes a drastic reduction in dystrophin-associated glycoproteins, which renders muscle fibres more susceptible to necrosis. Following the biochemical and cell biological characterization of the dystrophin-glycoprotein complex, several mass spectrometry-based proteomic studies have investigated global changes in dystrophin-deficient muscle tissues. This review briefly outlines the basic domain structure of Dp427 and the composition of the dystrophin-associated glycoprotein complex from skeletal muscle. A detailed discussion of recent proteomic analyses of the purified dystrophin-glycoprotein complex is included, as well as a summary of mass spectrometric surveys of dystrophic specimens. The study of these new areas of muscle proteomics tends to improve our understanding of the normal function of dystrophin in contractile fibres and better define the molecular mechanism of X-linked muscular dystrophy.

냉수성 질병에 대한 제주 양식 돌돔, Oplegnathus fasciatus의 병리조직학적 관찰

The outbreak of haemorrhagic speticemia and dermal lesions in cultured Rock sea breem in Jeju Island are frequently associated with keratitis. Prolonged infection leads to the symptoms accompanied by necrosis of fin and skin and the fishes died. Present study aims to study the histopathological changes of diseased fish muscle tissue. The tissue at the initial stage of infection showed normal muscular texture, however in the late stages of infection, muscular lesion had been expanded and hence, necrosis had progressed deeply into muscle tissue. Mild tissue in caudal fin was found with more necrosis, and gill tissues were also collapsed. In Kidney, renal tubules were teared along with tissue destruction (Espada, J et al, 1993). Hence in the present study, we examined the histopathological variation of the infection fishes, and this basic data would be used for future research of in haemorrhagic specticemia and dermal diseases.

ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains

BackgroundObesity-associated organ-specific pathological states can be ensued from the dysregulation of the functions of the adipose tissues, liver and muscle. However, the influence of genetic differences underlying gross-compositional differences in these tissues is largely unknown. In the present study, the analytical method of ATR-FTIR spectroscopy has been combined with a genetic approach to identify genetic differences responsible for phenotypic alterations in adipose, liver and muscle tissues.ResultsMice from 29 BXD recombinant inbred mouse strains were put on high fat diet and gross-compositional changes in adipose, liver and muscle tissues were measured by ATR-FTIR spectroscopy. The analysis of genotype-phenotype correlations revealed significant quantitative trait loci (QTL) on chromosome 12 for the content of fat and collagen, collagen integrity, and the lipid to protein ratio in adipose tissue and on chromosome 17 for lipid to protein ratio in liver. Using gene expression and sequence information, we suggest Rsad2 (viperin) and Colec11 (collectin-11) on chromosome 12 as potential quantitative trait candidate genes. Rsad2 may act as a modulator of lipid droplet contents and lipid biosynthesis; Colec11 might play a role in apoptopic cell clearance and maintenance of adipose tissue. An increased level of Rsad2 transcripts in adipose tissue of DBA/2J compared to C57BL/6J mice suggests a cis-acting genetic variant leading to differential gene activation.ConclusionThe results demonstrate that the analytical method of ATR-FTIR spectroscopy effectively contributed to decompose the macromolecular composition of tissues that accumulate fat and to link this information with genetic determinants. The candidate genes in the QTL regions may contribute to obesity-related diseases in humans, in particular if the results can be verified in a bigger BXD cohort.

AB1126 Whole-body magnetic resonance imaging in the assessment of disease activity in juvenile dermatomyositis

BackgroundMagnetic resonance imaging (MRI) has been suggested as a valuable technique for diagnosis of myositis because of its high sensitivity to the presence of inflammation. So far all MRI studies...

Muscle tissue changes with aging.

Sarcopenia is characterized by a progressive generalized decrease of skeletal muscle mass, strength and function with aging. Recently, the genetic determination has been associated with muscle mass and muscle strength in elderly. These two phenotypes of risk are the most commonly recognized and studied for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45-90% for muscle mass. It is well known that the development and maintenance of muscle mass in early adulthood reduces the risk of developing sarcopenia and leads to a healthy aging. For that reason it seems important to identify which genetic factors interact with aging and in particular with the musculoskeletal response to exercise in such individuals. This review is designed to summarize the most important and representative studies about the possible association between certain genetic polymorphisms and muscle phenotypes in older populations. Also we will focuses on nutrition and some concerns associated with aging, including the role that exercise can have on reducing the negative effects of this phenomenon. Some results are inconsistent between studies and more replication studies underlying sarcopenia are needed, with larger samples and with different life cycles, particularly in the type and level of physical activity throughout life. In future we believe that further progress in understanding the genetic etiology and the metabolic pathways will provide valuable information on important biological mechanisms underlying the muscle physiology. This will enable better recognition of individuals at higher risk and the ability to more adequately address this debilitating condition.

A safety study of inactivated Enterovirus 71 vaccine

Enterovirus 71 (EV71) is one of the major causative agents for hand, foot and mouth disease (HFMD) in childhood. Nowadays, HFMD or EV71 infections have already become an important public health issue throughout the world. Vaccination may be the most effective measure to control the transmission of the virus. Therefore, to pave EV71 vaccine into human clinical trial, in the present study a comprehensive preclinical safety assessment of inactivated EV71 vaccine including single- and repeat-dose toxicity studies were conducted in rats and cynomolgus monkeys. No abnormal findings were observed in rats following single intramuscular administration with EV71 vaccine (640 U). The results also showed no obvious systemic toxicities from four repetitive intramuscular injections, with a 14-d interval, of two dosages of EV71 vaccine in the two animal species. Antinuclear antibody response was not detected after the repeated administrations. Histopathological examination demonstrated the minimal to severe inflammatory changes in muscle tissues of the injection sites in EV71 vaccine-injected animals and most of findings have been improved over time. Furthermore, test article could induce highly EV71-specfic neutralizing antibody response in both animal species. Taken together, these data suggested a favorable safety profile for inactivated EV71 vaccine and supported this product to enter human phase I clinical trial.

Investigation of changes in body composition, metabolic profile and skeletal muscle functional capacity in ischemic stroke patients: the rationale and design of the Body Size in Stroke Study (BoSSS)

BackgroundStroke is steadily increasing in prevalence. Muscle tissue wasting and functional changes are frequently observed in stroke, but this has not been studied in detail yet. There is a lack of data to support guideline recommendations on how to target muscle wasting in stroke patients. We hypothesise that pathophysiological metabolic profiles and muscle functional and structural impairment are developing in stroke patients, which are associated with stroke severity and outcome after stroke.MethodsThe Body Size in Stroke Study (BoSSS) is a prospective, longitudinal observation study that will explore associations between the metabolic profile, body tissue wasting and particular metabolic and functional changes in skeletal muscle tissue in stroke patients. Consecutive patients with acute stroke (n = 150) will be enrolled due to lacunar or territorial ischemic infarct in the area of the middle cerebral artery. Patients will be studied at annual intervals after 12 and 24 months. For comparison, healthy controls of similar age and patients with chronic heart failure will be used as control groups. The main objective is to study changes in body composition in stroke patients. Secondary, the study will focus on changes in insulin sensitivity of adipose tissue and skeletal muscle. Furthermore, measurements of endothelial function and peripheral blood flow will provide insight in the vascular regulation in stroke patients.ConclusionThis study will be the largest observational study providing insights into the metabolic and functional changes of muscle tissue in patients with acute ischemic stroke. The new data will increase our understanding of the pathophysiologic tissue wasting in stroke disease and help to develop new therapeutic strategies.

Effect of 808 nm low-level laser therapy in exercise-induced skeletal muscle fatigue in elderly women

Aging process involves several structural changes in muscle tissue which lead to decrease in musculoskeletal function. One of the most common physiological modifications is the increase in fatigability in elderly people, which leads to inability to maintain strength and motor control. In this context, low-level laser therapy (LLLT) has demonstrated positive results in reducing fatigue during physical exercise. Thus, this study aimed to investigate the effects of LLLT on skeletal muscle fatigue in elderly women. Twenty-four subjects divided in two groups entered a crossover randomized triple-blinded placebo-controlled trial. Active LLLT (808nm wavelength, 100mW, energy 7J) or an identical placebo LLLT was delivered on the rectus femoris muscle immediately before a fatigue protocol. Subjects performed a fatigue protocol which consisted of voluntary isotonic contractions of knee flexion-extension performed with a load corresponding to 75% of 1-MR (Maximum Repetition) during 60s. Surface electromyography (SEMG) signals were recorded from rectus femoris muscle of dominant lower limb to evaluate peripheral fatigability using median frequency analysis of SEMG signal. The number of repetitions of flexion-extension during fatigue protocol was also compared between groups. The values of median frequency were used to calculate the slope coefficient. The results showed no difference in the slope comparing placebo LLLT and active LLLT groups (p = 0.293). However, a significant difference was observed in the number of repetitions between groups, after active LLLT, subjects demonstrated significantly higher number of repetitions (p = 0.047). In this study, LLLT was efficient in increasing the mean number of repetitions during knee flexion-extension exercise, although results have not shown delay electromyographic fatigue.

Mechanism of Body Weight Reducing Effect of Oral Boric Acid Intake

Objective. The effect of oral boric acid intake on reducing body weight has been previously demonstrated although the mechanism has been unclear. This research study reveals the mechanism. Subjects. Twelve mice were used, in groups of six each in the control and study groups. For five days, control group mice drank standard tap water while during the same time period the study group mice drank tap water which contains 0.28 mg/250 mL boric acid. After a 5-day period, gene expression levels for uncoupling proteins (UCPs) in the white adipose tissue (WAT), brown adipose tissue (BAT), and skeletal muscle tissue (SMT) and total body weight changes were analyzed. Results. Real time PCR analysis revealed no significant change in UCP3 expressions, but UCP2 in WAT (P: 0.0317), BAT (P: 0.014), and SMT (P: 0.0159) and UCP1 in BAT (P: 0.026) were overexpressed in the boric acid group. In addition, mice in the boric acid group lost body weight (mean 28.1%) while mice in the control group experienced no weight loss but a slight weight gain (mean 0.09%, P < 0.001). Conclusion. Oral boric acid intake causes overexpression of thermogenic proteins in the adipose and skeletal muscle tissues. Increasing thermogenesis through UCP protein pathway results in the accelerated lipolysis and body weight loss.

Patterns of Failure in Patients Treated With Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy (HT) for Head-and-Neck Squamous Cell Carcinoma (HNSCC): Results of a Prospective Trial

mass index (BMI) is associated with improved recovery from CRT and survival. Emerging evidence suggests that BMI may be used in conjunction with other body composition indices, including skeletal muscle and visceral adipose loss to individualize nutritional assessment and survival prognostication. This study evaluates the effect of body composition changes on survival in a population-based cohort of patients with locally advanced HNC treated with curative intent. Materials/Methods: A retrospective review was performed on 43 patients with Stage III/IV HNC treated with radical RT chemotherapy between 2007 and 2010. Preand post-treatment CT datasets encompassing the L3 vertebral body were available in 36 cases. Visceral adipose tissue and skeletal muscle cross sectional area (cm) were contoured at the L3 level with Eclipse v.10.0, using established thresholds of Hounsfield units. Pre and post treatment weight and BMI were recorded. Body composition indices analyzed included pre-treatment BMI, changes in skeletal muscle and visceral adipose tissue. Results: Median follow-up was 23.1 months. Mean disease specific survival (DSS) was 37.6 months. The average weight loss on treatment was 5.1kg. 72% of patients had acute grade 2 dysphagia and 79% had grade 2 mucositis. The median time from end of treatment to repeat CT scan was 3.1 months. Of 36 cases with preand postCT scans, the mean skeletal muscle loss was 19.5 cm and mean visceral adipose loss was 54.0 cm. Mean DSS was 38.3 months (95% CI 32.8-43.9) in patients with pretreatment BMI 25 kg/m vs. 30.2 months (95% CI 23.4-37.0) with BMI <25 kg/m (P Z NS). Mean DSS was longer in patients with post-treatment skeletal muscle loss <20 cm and visceral adipose loss <50%, but the differences were not statistically significant (Table). Conclusion: The observation of a trend toward improved survival in HNC patients with high pre-treatment BMI is consistent with other reports. Though not statistically significant, a trend toward longer survival was also observed with lower post-treatment skeletal muscle and visceral adipose loss. These preliminary findings support the plan to expand the cohort to increase sample size, calculate lean body mass based on established regression models, and correlate body composition changes with survival.

Quality of raw and smoked fillets from clinically healthy Atlantic salmon, Salmo salar L., following an outbreak of pancreas disease (PD)

Pancreas disease (PD) is a viral disease of farmed salmonid fish, which causes huge economic losses. Pathological changes in skeletal muscle, pancreas and heart are hallmarks of PD. Stakeholders in the fish-smoking industry have claimed that fillets from PD-affected Atlantic salmon, Salmo salar L., are of poor quality. We therefore examined harvest-ready, clinically healthy Atlantic salmon from a population of fish previously affected by PD. Histopathological changes in skeletal muscle tissues ranged from minor to severe. Fillet quality measurements showed that fish with severe skeletal muscle changes provided a paler raw fillet and a yellowish and harder cold-smoked fillet than normal. PD had no significant effect on fillet gaping, bacteriological quality or off-odour development during storage. An unexpected finding was a significant subendocardial fibrosis in 23% of the PD-affected fish. The latter may indicate susceptibility to stress-related heart failure.

Sublethal propoxur toxicity to juvenile common carp (Cyprinus carpio L., 1758): biochemical, hematological, histopathological, and genotoxicity effects

The sublethal toxicological and genotoxic potential of propoxur, a widely used carbamate insecticide against household pests, in veterinary medicine, and in public health, was evaluated on carp as a model species (Cyprinus carpio L., 1758) using the erythrocyte micronucleus test. Based on the 96-h lethal concentration, 50% (LC50) data from the U.S. Environmental Protection Agency ECOTOX Database (10 mg/L), a sublethal exposure concentration of 5 mg/L was used under static bioassay laboratory conditions. Histopathological evaluation showed no significant changes in spleen, intestine, muscle, or skin tissues. However, the following conditions were recorded: hyperemia, branchitis in primary lamella, and telangiectasis, hyperplasia, fusion, epithelial lifting, and epithelial desquamation in secondary lamella of gill tissues; hemorrhage, destruction, prenephritis, and inflammation and desquamation in the tubules; edema in the kidney; passive hyperemia, albumin, and hydropic degeneration in the liver; and hyperemia, chromatolysis, and glial proliferation in brain tissues. No statistically significant increases in micronuclei frequencies were found. Hematological parameters showed decreased hematocrit values and mean corpuscular volume values, as well as increased erythrocyte and leukocyte counts compared with the control group (p < 0.01). Plasma glucose, cholesterol, triglycerides, phosphorus, sodium, total plasma protein, chloride, and aspartate aminotransferase levels were increased (p < 0.01). Only plasma calcium and potassium levels decreased in the experimental group. Propoxur has an ecotoxicological potential on fish, a nontarget organism.

Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: the relationship with diabetes and anaemia

Weight loss leading to cachexia is associated with poor treatment response and reduced survival in pancreatic cancer patients. We aim to identify indicators that allow for early detection that will advance our understanding of cachexia and will support targeted anti-cachexia therapies. A total of fifty pancreatic cancer patients were analysed for skeletal muscle and visceral adipose tissue (VAT) changes using computed tomography (CT) scans. These changes were related to physical characteristics, secondary disease states and treatment parameters. Overall, patients lost 1.72 (SD 3.29) kg of muscle and 1.04 (SD 1.08) kg of VAT during the disease trajectory (413 (SD 213) d). After sorting patients into tertiles by rate of VAT and muscle loss, patients losing VAT at > -0.40 kg/100 d had poorer survival outcomes compared with patients with < -0.10 kg/100 d of VAT loss (P= 0.020). Patients presenting with diabetes at diagnosis demonstrated significantly more and accelerated VAT loss compared with non-diabetic patients. In contrast, patients who were anaemic at the first CT scan lost significantly more muscle tissue and at accelerated rates compared with non-anaemic patients. Accelerated rates of VAT loss are associated with reduced survival. Identifying associated features of cachexia, such as diabetes and anaemia, is essential for the early detection of cachexia and may facilitate the attenuation of complications associated with cachexia.

Exercise training, genetics and type 2 diabetes-related phenotypes

Type 2 diabetes mellitus (T2DM) is at virtually pandemic levels world-wide. Diabetes has been referred to as 'a geneticist's nightmare'. However, dramatic advances in our understanding of the genetics of T2DM have occurred in the past 5years. While endurance exercise training and increased habitual physical activity levels have consistently been shown to improve or be associated with improved T2DM-related phenotypes, there is substantial interindividual variation in these responses. There is some evidence that T2DM-related phenotype responses to exercise training are heritable, indicating that they might have a genetic basis. Genome-wide linkage studies have not identified specific chromosomal loci that could account for these differences, and no genome-wide association studies have been performed relative to T2DM-related phenotype responses to exercise training. From candidate gene studies, there are relatively strong and replicated data supporting a role for the PPARγ Pro12Ala variant in the interindividual differences in T2DM-related phenotype responses to training. This is a potentially important candidate locus because it affects T2DM susceptibility, has high biological plausibility and is the target for the primary pharmaceutical method for treating T2DM. Is it time to conduct a hypothesis-driven large-scale exercise training intervention trial based on PPARγ Pro12Ala genotype with T2DM-related phenotypes as the primary outcome measures, while also assessing potential mechanistic changes in skeletal muscle and adipose tissue? Or would it be more appropriate to propose a smaller trial to address the specific skeletal muscle and adipose tissue mechanisms affected by the interaction between the PPARγ Pro12Ala genotype and exercise training?

Evaluation of dynamic changes of rabbit mulsle's restoration after damaging using acoustic radiation force impulse

Objective To observe the dynamic change of muscle tissue restoration after damaging at different observation time through acoustic radiation force impulse(ARFI).Methods According to different observation time,16 healthy rabbits were randomly divided into four groups,including before injury,1 day after injury,7 day after injury,14 day after injury.A homemade gravity hammer was used to establish damage model of rabbit gastrocnemius,then applied ARFI to observe changes of virtual touch tissue quantification (VTQ) of gastrocnemius.All the rabbits were executed after measurement,then the pathological changes of muscle tissue were observed under microscope.Results The VTQ of damaged muscle group were significantly higher than that of nomal muscle group( P ＜0.01),and VTQ of 1 day,7day,14 day group after injuried had significant difference between two groups (P ＜ 0.01).Through pathological examination,normal musule fibers were continual and there were not swelling and bleeding.One days after injury,muscle fibers were fractured,swollen,bleeding and congestive.7 days after injury,large areas of muscle cells were necrotic,and amounts of calcium salt depositsed.14 days after injury,lots of fiber cells proliferated,and the deposits of calcium obviously reduced.The results of ultrasound elastography were consistent with these of pathological.Conclusions ARFI can direct,noninvasively evaluate the changes of muscle tissue restoration after different time of injury,and provide objective basis for diagnosis and treatment. Key words: Ultrasonography; Muscle injuries; Acoustic radiation force impulse

Calpain inhibition attenuated morphological and molecular changes in skeletal muscle of experimental allergic encephalomyelitis rats

Muscle weakness and atrophy are important manifestations of multiple sclerosis (MS). To investigate the pathophysiological mechanisms of skeletal muscle change in MS, we induced experimental autoimmune encephalomyelitis (EAE) in Lewis male rats and examined morphological and molecular changes in skeletal muscle. We also treated EAE rats with calpepetin, a calpain inhibitor, to examine its beneficial effects on skeletal muscle damage. Morphological changes in muscle tissue of EAE rats included smaller and irregularly shaped muscle fibers and fibrosis. Western blot analysis demonstrated increased calpain:calpastatin ratio, inflammation-related transcription factors (nuclear factor-κB:inhibitor of κB α ratio), and proinflammatory enzymes (cyclooxygenase-2). TUNEL-positive myonuclei in skeletal muscle cells of EAE rats indicated cell death. In addition, markers of apoptotic cell death (Bax:Bcl-2 ratio and caspase-12 protein levels) were elevated. Expression of muscle-specific ubiquitin ligases (muscle atrophy F-box and muscle ring finger protein 1), was upregulated in muscle tissue of EAE-vehicle animals. Both prophylactic and therapeutic treatment with calpeptin partially attenuated muscle changes noted in EAE animals. These results indicate that morphological and molecular changes including apoptotic cell death and protein breakdown develop in skeletal muscle of EAE animals and that these changes can be reversed by calpain inhibition.

Microstructural histological changes in muscle tissue of goat kids in zones of abnormal heavy metal content

The results of investigating soil, water, feeds, and meat of goat kids for heavy metal content are given and microstructural histological changes in muscle tissue are studied.

Effect of Breed and Age on Histopathological Changes in Pig M. Semimembranosus

Effect of Breed and Age on Histopathological Changes in Pig M. SemimembranosusThe aim of the study was to determine the type and extent of histopathological changes in m. semimembranosus of Polish Landrace (PL), Polish Large White (PLW), Duroc, Pietrain, and Puławska pigs at 60, 90, 120, 150, 180 and 210 days of age. Changes in fibre size (atrophy, hypertrophy - giant fibres), changes in fibre shape (angular fibres), degenerative lesions (necrosis with phagocytosis) and connective tissue hypertrophy were evaluated. The presence of giant fibres was the only histopathological change observed in all age groups of PL, PLW, Duroc and Pietrain pigs, with the percentage of pigs with this type of pathology and the frequency of giant, atrophic and angular fibres increasing significantly with age. In Puławska pigs, giant fibres were only found in the oldest pigs aged 210 days. In these animals, giant fibres as well as atrophic fibres (at 180 and 210 days of age) and angular fibres (at 120, 150, 180 and 210 days of age) occurred in the smallest number of animals and were least extensive. Meanwhile, Pietrain pigs were characterized by a greater number of animals, a significantly greater proportion of giant fibres in all analysed age groups, and a greater proportion of atrophic fibres at 180 and 210 days of age compared to the other pig breeds under analysis. For connective tissue hypertrophy and necrosis with phagocytosis, the changes were not extensive. It is concluded that both the advancing age of the animals and selection of the pigs for increased leanness significantly increases the incidence of histopathological changes in muscle tissue, which may directly translate into pork quality.

Early muscle and brain ultrastructural changes in polymerase gamma 1‐related encephalomyopathy

Mutations affecting the mitochondrial DNA-polymerase gamma 1 (POLG1) gene have been shown to cause Alpers-Huttenlocher disease. Ultrastructural data on brain and muscle tissue are rare. We report on ultrastructural changes in brain and muscle tissue of two sisters who were compound heterozygous for the c.2243G>C and c.1879C>T POLG1 mutations. Patient 1 (16 years) presented with epilepsia partialis continua that did not respond to antiepileptic treatment. Neuroimaging showed right occipital and bithalamic changes. Light microscopy from a brain biopsy performed after 3 weeks suggested chronic encephalitis showing astro- and microgliosis as well as perivascular CD8-positive T-cells. However, immunosuppressive therapy failed to improve her condition. When her 17-year-old sister (patient 2) also developed epilepsy, an intensified search for metabolic diseases led to the diagnosis. On electron microscopy mitochondrial abnormalities mainly affecting neurons were detected in the brain biopsy of patient 1, including an increase in number and size, structural changes and globoid inclusions. In patient 2, light and electron microscopy on a muscle biopsy confirmed a mitochondrial myopathy, also revealing an increase in mitochondrial size and number, as well as globoid inclusions. Neurons may be the primary target of mitochondrial dysfunction in brains of patients with Alpers disease related to POLG1 mutations. During early disease stages, brain histopathology may be misleading, showing reactive inflammatory changes.