Statins induce biochemical changes in the Achilles tendon after chronic treatment

AbstractStatins have been widely prescribed as lipid-lowering drugs and are associated with tendon rupture. Therefore, this study aimed to evaluate the possible biochemical changes in the Achilles tendon of rats after chronic treatment with statins. Dosages of statins were calculated using allometric scaling with reference to the 80mg/day and 20mg/day, doses recommended for humans. The rats were divided into the following groups: treated with simvastatin (S-20 and S-80), treated with atorvastatin (A-20 and A-80), and the control group that received no treatment (C). Measurements of low-density lipoprotein (LDL) in the plasma were performed. The levels of non-collagenous proteins, glycosaminoglycans (GAGs) and hydroxyproline were quantified. Western blotting for collagen I was performed, and the presence of metalloproteinases (MMPs)-2 and -9 was investigated through zymography. The concentration of non-collagenous proteins in S-20 was less than the C group. There was a significant increase in pro-MMP-2 activity in A-80 group and in active MMP-2 in S-20 group compared to the C group. A significant increase in latent MMP-9 activity was observed in both the A-80 and S-20 groups when compared to C group. In the A-20 group, there was a lower amount of collagen I in relation to C group. In addition, a higher concentration of hydroxyproline was found in the S-20 group than the C group. The analysis of GAGs showed a significant increase in the A-20 group when compared to C group. The treatment induced remarkable alterations in the Achilles tendon and the response of the tissue seems to depend of the used statin dosage. The presence of MMP-2 and MMP-9 is evidence of the degradation and remodeling processes in the extracellular matrix of the tendons. Our results show that statins induce imbalance of extracellular matrix components and possibly induce microdamage in tendons

Estudo morfológico da sínfise púbica de ratos e camundongos durante a gravidez

O objetivo desse estudo foi avaliar as diferenças existentes na sínfise púbica de camundongos e ratos fêmeas, grávidas e não grávidas, descrevendo as alterações morfológicas ocorridas na articulação com a finalidade de entender os movimentos apresentados pela articulação ao longo da gestação. Para tal, as sínfises foram coletadas de camundongos fêmeas grávidas no 6º, 12º e 18º dias de gestação, e nas ratas com 18 dias de gestação. Foram fixadas em paraformoldeído e a seguir descalcificadas em solução de Morse. Na sequência, as peças foram incluídas em parafina. Cortes de 7 micrômetros foram realizados e corados em Picrosirius e Resorcina-Fucsina. A coloração com Picrosirius evidenciou em camundongos fêmeas virgens a presença de fibras grossas de colágeno diferente dos outros grupos de camundongos, os quais apresentaram fibras finas. A análise de fibras elásticas mostrou que, com o decorrer da gestação, estas aumentam em espessura e número. Em ratas com 18 dias de gestação foi observado o aparecimento de tecido conjuntivo fibroso no disco de cartilagem hialina, aumentando assim, o espaço inter-púbico e modificando a estrutura de sincondrose encontrada nos animais virgens. Observou-se também aumento no diâmetro e quantidade de fibras elásticas em relação às ratas virgens. Podemos concluir que a articulação de camundongos fêmeas grávidas passam por transformações estruturais qualitativas e quantitativas ao longo da gravidez. Em ratas prenhas, além do aumento de fibras elásticas e da distância entre os ossos do quadril, a articulação diferenciou-se pelo aparecimento de tecido conjuntivo fibroso para facilitar o parto.The objective of this study was to assess the existing differences in the pubic symphysis of female rats and mice, pregnant and non pregnant, describing the morphological alterations occurred in the joint and understanding the movements shown during pregnancy. The pubic symphysis were collected from female pregnant mice on the 6th, 12th and 18th days of pregnancy, and from rats with 18 days of pregnancy. They were fixed in paraformoldehyde and following decalcificated with Morse's solution. The samples were then, included in paraffin. Seven micrometers slices were made and stained with Picrosirius and Resorcin-Fuchsin. The Picrosirius staining had shown, in virgin female mice, the presence of thick collagen fibers different from the other groups of mice, which presented thin fibers. The analysis of elastic fibers showed that, with the progress of pregnancy there is an increase in their thickness and number. In rats with 18 days of pregnancy, an appearance of fibrous conjunctive tissue on the hyaline cartilage disc was observed, enlarging the inter-pubic space and modifying the synchondrosis structure found in the virgin animals. It was also observed an increase in diameter and amount of elastic fibers comparing to virgin rats. We conclude that the pregnant female mice's joint undergoes transformations in structure, quality and amount during the pregnancy. In pregnant rats, besides the increase of elastic fibers and the distance between the hip's bone, the joint had differred by the appearance of fibrous conjunctive tissue, thus making the birth easier

Birefringence Of Collagen Fibres In Rat Calcaneal Tendons Treated With Acupuncture During Three Phases Of Healing.

Birefringence is an optical anisotropy that is investigated by polarisation microscopy, and has been valuable for the study of the oriented organisation of collagen fibres in tendons. However, the application of this technology to evaluate the effect of different acupuncture points during tendon healing has not yet been described. To evaluate the concentration of non-collagenous proteins (NCP) and birefringence in rat calcaneal tendons following injury during the three different phases of healing: inflammatory (7th day), proliferative (14th day), and remodelling (21st day). Tendons of 120 Wistar rats were tenotomised and left untreated (teno group, n=24), treated with manual acupuncture at ST36 (ST36 group, n=24), BL57 (BL57 group, n=24) or ST36+BL57 (SB group, n=24), or treated with electroacupuncture at ST36+BL57 (EA group, n=24). Tendon samples were collected at 7, 14 and 21 days after injury (n=8 per group). NCP concentrations were measured using the Bradford method (n=4 each) and birefringence was examined using polarisation microscopy and image analysis (n=4 each). Comparison was also made with healthy (non-tenotomised) tendons in a subgroup of rats (n=4 each). Manual acupuncture at ST36 and BL57 increased molecular organisation of collagen fibres on day 14 and 21 after injury. Isolated use of BL57 and ST36 also increased collagen fibre organisation when examined on day 14 and 21, respectively. No significant increase in NCP concentration was observed in any of the treated tenotomised groups. Acupuncture, through putative anti-inflammatory and mechanotransductor effects, may have a role in strengthening tendons and increasing resistance to re-rupture.3427-3

Alterations In The Achilles Tendon After Inflammation In Surrounding Tissue.

To analyze the characteristics of the Achilles tendon of rats after induction of localized inflammation in the rat paw. IN OUR STUDY THREE GROUPS WERE USED: inflamed group with carrageenan in rat paw (G1); saline group (G2) and control group (G3). After 4 hours the animals were euthanized and the Achilles tendon removed. No significant differences were observed in the analysis of non-collagenous proteins, glycosaminoglycans and hydroxyproline in the groups but a tendency of reduction was verified in G1. As regards the organization of collagen molecules, no differences were observed between groups. With respect to MMPs activity, a stronger presence of the active isoform of MMP-2 in G1 was observed, suggesting that the remodeling was occurring. Thus, we conclude that the inflammatory process in rat paw may affect the remodeling of tendons located near the inflamed site. Level of Evidence I, Prognostic Studies - Investigating the Effect of a Patient Characteristic on the Outcome of Disease.20266-

Biochemical And Morphological Alterations In The Achilles Tendon Of Mdx Mice.

Dystrophin-deficient muscles have repeated cycles of necrosis and regeneration, being susceptible to injury induced by muscle contractions. Some studies have demonstrated that tendons are also affected in mdx mice, based especially on the changes in biomechanical properties arising from the respective linked muscles. However, most studies have focused only on alterations in the myotendinous junction. Thus, the purpose of this work was to study biochemical and morphological alterations in the Achilles tendons of 60-day-old mdx mice. Hydroxyproline quantification, showed higher collagen concentration in the mdx mice as compared with the control. No difference between the tendons of both groups was found in the noncollagenous proteins dosage, and in the amount of collagen type III detected in the western blotting analysis. The zymography for gelatinases detection showed higher amounts of metaloproteinase-2 (active isoform) and of metalloproteinase-9 (latent isoform) in the mdx mice. Measurements of birefringence, using polarization microscopy, showed higher molecular organization of the collagen fibers in the tendons of mdx mice in comparison to the control group, with presence of larger areas of crimp. Ponceau SS-stained tendon sections showed stronger staining of the extracellular matrix in the mdx groups. Toluidine blue-stained sections showed more intense basophilia in tendons of the control group. In morphometry, a higher number of inflammatory cells was detected in the epitendon of mdx group. In conclusion, the Achilles tendon of 60-day-old mdx mice presents higher collagen concentration and organization of the collagen fibers, enhanced metalloproteinase-2 activity, as well as prominent presence of inflammatory cells and lesser proteoglycans.7885-9

Anatomia de A a Z: Anatomia de A a Z - Desvendando a terminologia anatômica nas redes sociais: Relato de experiência

Os termos médicos utilizados na morfologia eram provenientes de um nome próprio, com o intuito de homenagear os que descobriram ou apresentaram a estrutura anatômica, conhecidos como epônimos. Buscando unificar a linguagem anatômica e facilitar o processo de ensino, em 1989 foi criado o Comitê Federativo Internacional de Terminologia Anatômica (FICAT), cujo propósito era revisar os epônimos e atualizar a terminologia anatômica. Com o objetivo de apresentar os fundamentos e conhecimentos sobre a origem das terminologias anatômicas nas mídias sociais, a Liga Acadêmica de Anatomia da Universidade Federal de Alfenas (LAANAT/UNIFAL-MG), por meio do projeto de extensão “Anatomia de A a Z”, divulgou conhecimentos científicos acerca da etimologia anatômica. Foram feitas postagens semanais no Instagram e no Facebook, a partir de publicações elaboradas pelos ligantes, supervisionadas pelos professores coordenadores e desenvolvidas no aplicativo Canva. Cada postagem seguiu sequencialmente as letras do alfabeto (de A a Z) e eram compostas da etimologia de duas estruturas anatômicas. Frente a uma análise de dados, observamos que em 23 publicações, alcançamos 712 curtidas, 194 compartilhamentos, 44publicações salvas, 4739 contas alcançadas e 6608 impressões. A LAANAT promoveu, de forma clara e objetiva, a divulgação de conhecimentos das terminologias anatômicas ao público geral.The medical terms used in morphology were derived from proper nouns to honor those who discovered or presented the anatomical structure, known as eponyms. In 1989, anatomists founded the Federative International Program on Anatomical Terminologies (FICAT) to unify anatomical language and facilitate the teaching process by reviewingeponyms and updating nomenclature. Intending to present the fundamentals and knowledge about the origin of anatomical terminologies on social media, the Academic League of Anatomy at the Federal University of Alfenas (LAANAT/UNIFAL-MG), through the extension project “Anatomy from A to Z” disseminated scientific knowledge about anatomical etymology. Weekly posts were made on Instagram and Facebook, based on publications elaboratedby the League members, supervised by the professors, and developed on the Canva application. Each post sequentially followed the letters of the alphabet (from A to Z) and consisted of the etymology of two anatomical structures. In analyzing the data, we observed that in 23 publications, we achieved 712 likes, 194 shares, 44 saved posts, 4739 reached accounts, and 6608 prints. LAANAT promoted, clearly and objectively, the dissemination of knowledge of anatomical terminologies to the general public

Electroacupuncture Increases The Concentration And Organization Of Collagen In A Tendon Healing Model In Rats.

The aim of this study was to investigate the effect of electroacupuncture (EA) on the composition and organization of the extracellular matrix of the rat Achilles tendon after a partial transection during the proliferative phase of healing. Wistar rats were divided into three groups: rats that were not tenotomized (G1), tenotomized rats (G2), and rats that were tenotomized and submitted to EA (G3). EA was applied 15 days after injury at the ST36 and BL57 acupoints for 20 min, three times per week on alternate days for a total of six sessions. Biochemical analyses were performed using non-collagenous proteins, glycosaminoglycans, and hydroxyproline quantifications. An analysis of metalloproteinase-2 was carried out by zymography. The general organization of the extracellular matrix and the metachromasy of the tendons were analyzed under light microscopy. The organization of the bundles of collagen fibers was analyzed by birefringence analysis. The results showed that EA did not alter the concentration of non-collagenous proteins or glycosaminoglycans or the enzymatic activity of metalloproteinase-2 in the transected tendons. However, the concentration of hydroxyproline was significantly increased when these tendons were treated by EA. The analysis of birefringence showed a higher organization of collagen fibers in the group treated by EA. These results indicate, for the first time, that EA may offer therapeutic benefits for the treatment of tendon injuries by increasing the concentration of collagen and by inducing a better molecular organization of the collagen fibers, which may improve the mechanical strength of the tendon after injury.53542-

Protocol On Induction Of Tmj Articular Disc Degeneration In Rats By Utilization Of Botulinum Toxin.

To develop a model of experimental degeneration in the articular disc of the TMJ of rats through the use of botulinum toxin that can be used in future studies of degenerative diseases on fibrocartilage. Aiming at the above-mentioned objective, 12 Lewis male rats were used and divided into two groups: CG, control group and DG, group of animals to which the botulinum toxin was administered (6 units/kg). The morphological analysis was carried out utilizing histological cuts stained with hematoxyline-eosine, toluidine blue and Picrosirius; the biochemical analysis was made by SDS-polyacrylamide gel electrophoresis. The DG showed peculiar characteristics regarding a degeneration joint disk, compatible with those described in literature as: reduction of cells number, general disorganization of cells direction and extracellular matrix, increase in glycosaminoglycans content and degradation of the tissue collagen. Based on the morphological and biochemical results, it was concluded that the proposed degeneration model showed to be satisfactory for futures studies of injuries and fibrocartilage regeneration processes.55530-