Fibro-adipogenesis in Injured Rotator Cuff Muscle

Purpose of Review Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue. Recent Findings Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression. Summary The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.

ABHRAK BHASMA AND SIO2 INFLUENCED MOBILITY OF LIPIDS IN LIVER AND KIDNEY OF CCL4 INDUCED ACUTELY INTOXICATED ALBINO RAT

In our earlier studies on CCl4 induced acute toxicity model (CCl4 3ml/kg body wt). Abhrak bhasma protects fatty degeneration of liver and associated nephrotoxicity in male albino rats. It had shown to function through production and management of free radicals (Teli and Kanase, 2020a, b). To study further the paths of Abhrak Bhasma mediated protection of acute hepatotoxicity and associated nephrotoxicity, liver, kidney and serum lipid contents were studied in present work. It shows no lipid accumulation in liver or kidney of normal rats by Abhrak Bhasma (10, 20, 30 and 40mg doses). But a same dose of silica in pure form (SiO2) is hepato and nephrotoxic in high doses in normal male albino rat. In acutely intoxicated rat also all the doses of Abhrak Bhasma influenced lipid contents of liver, kidney and serum show the protection of liver from fatty degeneration and also associated nephrotoxicity. Doses 30 and 40mg normalized the contents from liver, kidney and serum. The results are discussed to reveals the probable mode of action of Abhrak Bhasma.

The Effectiveness of Purslane Extract Provision on Liver of White Rats (Rattus norvegicus) with High Fat Diet

Most animal owners provide fatty food with high cholesterol level that exceeds the needs of their pets. The pattern of giving a high-fat diet causes interference with the cholesterol synthesis in the body. It can damage the liver by causing fatty degeneration, hepatic cirrhosis, and eventually necrosis of the liver. The purpose of the current study was to determine the effectiveness of Purslane extract (Portulaca oleracea L.) on the liver histopathological image of white rats (Rattus norvegicus) with a high-fat diet. The current study used an experimental method with a completely randomized design on 20 males white mouses (Rattus norvegicus) divided into five treatment groups. There were two control groups, the first group received standard feed (Pellet) and Carboxymethyl Cellulose Sodium 1%, while the second was given standard feed and a high-fat diet. Three treatment groups which included P1, P2, P3 were given standard feed, a high-fat diet, and purslane extract solution with 54 mg/day, 108 mg/day, and 216 mg/day, respectively. Research results from the mean rank of fatty degeneration which was measured using the Kruskal Wallis test presented significant differences, and the results from the mean of fatty degeneration using the Mann Whitney test did not indicate any significant difference. Liver cell necrosis from the two tests presented a significant difference. Purslane extract (Portulaca oleracea L.) was confirmed to be effective in reducing or decreasing hepatocyte cell damage after receiving a high-fat diet.

Muscular and Tendon Degeneration after Achilles Rupture: New Insights into Future Repair Strategies

Achilles tendon rupture is a frequent injury with an increasing incidence. After clinical surgical repair, aimed at suturing the tendon stumps back into their original position, the repaired Achilles tendon is often plastically deformed and mechanically less strong than the pre-injured tissue, with muscle fatty degeneration contributing to function loss. Despite clinical outcomes, pre-clinical research has mainly focused on tendon structural repair, with a lack of knowledge regarding injury progression from tendon to muscle and its consequences on muscle degenerative/regenerative processes and function. Here, we characterize the morphological changes in the tendon, the myotendinous junction and muscle belly in a mouse model of Achilles tendon complete rupture, finding cellular and fatty infiltration, fibrotic tissue accumulation, muscle stem cell decline and collagen fiber disorganization. We use novel imaging technologies to accurately relate structural alterations in tendon fibers to pathological changes, which further explain the loss of muscle mechanical function after tendon rupture. The treatment of tendon injuries remains a challenge for orthopedics. Thus, the main goal of this study is to bridge the gap between clinicians’ knowledge and research to address the underlying pathophysiology of ruptured Achilles tendon and its consequences in the gastrocnemius. Such studies are necessary if current practices in regenerative medicine for Achilles tendon ruptures are to be improved.

Protein-synthesizing, bile-forming, urea-forming and carbohydrate functions in cows with fatty degeneration of the liver

In dairy farms of Ukraine, where highly productive dairy cows are kept, liver lesions are often diagnosed in the postpartum period. Postmortem studies of the liver of cows that were forcibly slaughtered showed that in mostly animals were diagnosed with fatty degeneration of the liver. The main causes of fatty hepatosis were violations of the structure of rations, imbalance of feeding on essential nutrients and biologically active substances, low content of easily digestible carbohydrates and high protein content. The study was performed on cows aged 4–5 years with productivity for the previous lactation of 5.600–7.500 L of milk, in a winter-stall period of keeping, 2–3 weeks after calving. According to clinical and biochemical blood tests, two groups of cows were formed – 50 clinically healthy and 50 cows with fatty liver disease. In cows diagnosed with fatty liver degeneration, the disease was manifested by decreased productivity and fatness, loss of appetite, oppression, hypotony of the rumen, reticulum and omasum. In some cows, there was pain at the liver area, increasing boundaries of hepatic dullness, jaundice of the visible mucous membranes and sclera. The blood serum of all cows with fatty liver disease established a decrease in albumin content, indicating impaired protein synthesis function of the liver. In some cows, the content of total protein in the serum increased due to globulin fractions, mainly gamma globulins. The ratio between the content of albumins and globulins decreased, which indicates the development in the blood of sick animals dysproteinemia. The development of fatty infiltration of the liver caused an increase in the concentration of bile acids in the serum of all sick cows. This is due to reduced conjugation and excretion of cholates by affected hepatocytes from the bile capillaries. The formation, absorption, conjugation, and excretion of bilirubin in the bile is disturbed, which causes the accumulation of total and conjugated bilirubin in the serum of sick animals. The cholesterol content in the blood of cows decreased, caused a violation of the esterification of its esters by hepatocytes. The established changes in the content of bile acids, total and conjugated bilirubin, and cholesterol in the blood of sick cows indicate a violation of bile secretion, bile production, and cholestasis development. In some cows with fatty liver degeneration, urea formation function and carbohydrate function are impaired, leading to a decrease in blood urea content and glucose.

Subsidence of Interbody Cage Following Oblique Lateral Interbody Fusion: An Analysis and Potential Risk Factors

Study Design Retrospective cohort study Objectives This study aimed to report the incidence and potential risk factors of polyetheretherketone (PEEK) cage subsidence following oblique lateral interbody fusion (OLIF) for lumbar degenerative diseases. We proposed also an algorithm to minimize subsidence following OLIF surgery. Methods The study included a retrospective cohort of 107 consecutive patients (48 men and 59 women; mean age, 67.4 years) who had received either single- or multi-level OLIF between 2012 and 2019. Patients were classified into subsidence and non-subsidence groups. PEEK cage subsidence was defined as any violation of either endplate from the computed tomography scan in both sagittal and coronal views. Preoperative variables such as age, sex, body mass index, bone mineral density (BMD) measured by preoperative dual-energy X-ray absorptiometry, smoking status, corticosteroid use, diagnosis, operative level, multifidus muscle cross-sectional area, and multifidus muscle fatty degeneration were collected. Age-related variables (height and length) were also documented. Univariate and multivariate logistic regression analyses were used to analyze the risk factors of subsidence. Results Of the 107 patients (137 levels), 50 (46.7%) met the subsidence criteria. Higher PEEK cage height had the strongest association with subsidence (OR = 9.59, P < .001). Other factors significantly associated with cage subsistence included age >60 years (OR = 3.15, P = .018), BMD <−2.5 (OR = 2.78, P = .006), and severe multifidus muscle fatty degeneration (OR = 1.97, P = .023). Conclusions Risk factors for subsidence in OLIF were age >60 years, BMD < −2.5, higher cage height, and severe multifidus muscle fatty degeneration. Patients who had subsidence had worse early (3 months) postoperative back and leg pain.

Focal fatty sparing as an indicator of higher-grade fatty liver assessed by attenuation imaging: a prospective clinical study in NAFLD population

Background As part of a prospective clinical study, the degree of hepatic fatty degeneration was quantified in a patient population with nonalcoholic fatty liver disease and sonographically diagnosed with hepatic steatosis using attenuation imaging. Methods A total of 113 patients with hepatic steatosis were examined, of whom 35 showed focal fatty sparing. Patients with the condition after right nephrectomy, other known liver diseases, and relevant alcohol consumption were excluded from the evaluation. B-scan sonography and sonographic quantification of steatosis content using attenuation imaging (Aplio i800 Canon Medical Systems) were performed. Attenuation imaging is a new ultrasound-based measurement technique that allows objective detection and quantification of hepatic steatosis. Results The prevalence of focal fatty sparing was 31.0% in the patient population examined. Patients with focal fatty sparing showed a statistically significantly higher attenuation coefficient in contrast to patients without focal fatty sparing (0.79 ± 0.10 vs. 0.66 ± 0.09 dB/cm/MHz, p < 0.0001). Conclusion Detection of focal fatty sparing is associated with an increased attenuation coefficient and is thus an expression of higher-grade hepatic fatty degeneration. Patients with focal fatty sparing are more often male and have a higher BMI and a larger liver than patients with nonalcoholic fatty liver disease without focal fatty sparing.

Discovery of the First in Class 9-N-Berberine Derivative as Hypoglycemic Agent with Extra-Strong Action

Berberine is well known for its ability to reduce the blood glucose level, but its high effective dose and poor bioavailability limits its use. In this work we synthesized a new derivative of berberine, 9-(hexylamino)-2,3-methylenedioxy-10-methoxyprotoberberine chloride (SHE-196), and analyzed the profile of its hypoglycemic effects. Biological tests have shown that the substance has a very pronounced hypoglycemic activity due to increased insulin sensitivity after single and multiple dosing. In obese type 2 diabetes mellitus (T2DM) mice, it was characterized by improved glucose tolerance, decreased fasting insulin levels and sensitivity, decreased total body weight and interscapular fat mass, and increased interscapular brown fat activity. All these effects were also confirmed histologically, where a decrease in fatty degeneration of the liver, an improvement in the condition of the islets of Langerhans and a decrease in the size of fat droplets in brown adipose tissue were found. Our results indicate that 9-(hexylamino)-2,3-methylenedioxy-10-methoxyprotoberberine chloride could be the first in a new series of therapeutic agents for the treatment of diabetes mellitus.

CORRELATION BETWEEN LOW BACK PAIN DUE TO FATTY DEGENERATION AND SEX AND AGE: STUDY BY MRI

ABSTRACT Objective: To correlate low back pain caused by fatty degeneration, visualized by magnetic resonance imaging (MRI), with sex and age. Methods: With a timeframe of 2015 to 2020, data on sex and age of fifty symptomatic patients with low back pain were collected from medical records and correlated with MRI analyses showing the occurrence of fatty infiltration in the paraspinal and erector muscles. Three trained observers, using the classification of Goutallier et al. (1994), analyzed five lumbar levels and the degree of injury. The Kolmogorov-Smirnov, Shapiro Wilk, Student's t, Mann-Whitney and Spearman correlation tests were used, all with a 5% significance level. Results: Among the cases, the L5-S1 level was found in all the images, with a prevalence of 46% of grades 1 and 2 and 24% in the five lumbar levels. Severity was present in a small portion (8%) of the injuries. There was a predominance of 78% women, with significantly more severe injuries in relation to the number of levels (p < 0.001) and injuries of a higher degree (p < 0.001). The age range was 14 to 38 years (mean = 26.70 ± 5.70 years), showing a significant and moderate correlation between the number of levels reached and a greater degree of degeneration (p < 0.001). Conclusion: Fatty degeneration as a cause of low back pain was significantly more severe in women in terms to the number of levels and the higher degree of injury. The number of levels and the severity of fatty degeneration were not correlated with the patient's age. Level of evidence II; Retrospective Study.