Neither too much nor too little: mitochondrial calcium concentration as a balance between physiological and pathological conditions.

Ca2+ ions serve as pleiotropic second messengers in the cell, regulating several cellular processes. Mitochondria play a fundamental role in Ca2+ homeostasis since mitochondrial Ca2+ (mitCa2+) is a key regulator of oxidative metabolism and cell death. MitCa2+ uptake is mediated by the mitochondrial Ca2+ uniporter complex (MCUc) localized in the inner mitochondrial membrane (IMM). MitCa2+ uptake stimulates the activity of three key enzymes of the Krebs cycle, thereby modulating ATP production and promoting oxidative metabolism. As Paracelsus stated, "Dosis sola facit venenum,"in pathological conditions, mitCa2+ overload triggers the opening of the mitochondrial permeability transition pore (mPTP), enabling the release of apoptotic factors and ultimately leading to cell death. Excessive mitCa2+ accumulation is also associated with a pathological increase of reactive oxygen species (ROS). In this article, we review the precise regulation and the effectors of mitCa2+ in physiopathological processes.

The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases.

Calcium (Ca2+) ions act as a second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. A lot of evidence demonstrates that the dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been shown.

The mitochondrial calcium uniporter complex-A play in five acts.

Mitochondrial Ca2+ (mitCa2+) uptake controls both intraorganellar and cytosolic functions. Within the organelle, [Ca2+] increases regulate the activity of tricarboxylic acid (TCA) cycle enzymes, thus sustaining oxidative metabolism and ATP production. Reactive oxygen species (ROS) are also generated as side products of oxygen consumption. At the same time, mitochondria act as buffers of cytosolic Ca2+ (cytCa2+) increases, thus regulating Ca2+-dependent cellular processes. In pathological conditions, mitCa2+ overload triggers the opening of the mitochondrial permeability transition pore (mPTP) and the release of apoptotic cofactors. MitCa2+ uptake occurs in response of local [Ca2+] increases in sites of proximity between the endoplasmic reticulum (ER) and the mitochondria and is mediated by the mitochondrial Ca2+ uniporter (MCU), a highly selective channel of the inner mitochondrial membrane (IMM). Both channel and regulatory subunits form the MCU complex (MCUC). Cryogenic electron microscopy (Cryo-EM) and crystal structures revealed the correct assembly of MCUC and the function of critical residues for the regulation of Ca2+ conductance.

Myonecrosis Induction by Intramuscular Injection of CTX.

Skeletal muscle, one of the most abundant tissue in the body, is a highly regenerative tissue. Indeed, compared to other tissues that are not able to regenerate after injury, skeletal muscle can fully regenerate upon mechanically, chemically, and infection-induced trauma. Several injury models have been developed to thoroughly investigate the physiological mechanisms regulating skeletal muscle regeneration. This protocol describes how to induce muscle regeneration by taking advantage of a cardiotoxin (CTX)-induced muscle injury model. The overall steps include CTX injection of tibialis anterior (TA) muscles of BL6N mice, collection of regenerating muscles at different time points after CTX injury, and histological characterization of regenerating muscles. Our protocol, compared with others such as those for freeze-induced injury models, avoids laceration or infections of the muscles since it involves neither surgery nor suture. In addition, our protocol is highly reproducible, since it causes homogenous myonecrosis of the whole muscle, and further reduces animal pain and stress. Graphical abstract.

Concept of healing of recurrent shoulder dislocation

This paper presents the main surgical techniques applied in the treatment of anterior recurrent shoulder dislocation, aiming the achievement of the normality of articulate movements. This was obtained by combining distinct surgical procedures, which allowed the recovery of a complete functional capacity of the shoulder, without jeopardizing the normality of movement, something that has not been recorded in the case of the tense sutures of the surgical procedures of Putti-Platt, Bankart, Latarjet, Dickson-O'Dell and others. The careful review of the methods applied supports the conclusion that recurrent shoulder dislocation can be cured, since cure has been obtained in 97% of the treated cases. However, some degree of limitation in the shoulder movement has been observed in most of the treated cases. Our main goal was to achieve a complete shoulder functional recovery, by treating simultaneously all of the anatomical–pathological lesions, without considering the so-called essential lesions. The period of post-operatory immobilization only last for the healing of soft parts; this takes place in a position of neutral shoulder rotation, since the use of vascular bone graft eliminates the need for long time immobilization, due to the shoulder stabilization provided by rigid fixation of the coracoid at the glenoid edge, as in the Latarjet's technique. Our procedure, used since 1959, comprises the association of several techniques, which has permitted shoulder healing without movement limitation. That was because of the tension reduction in the sutures of the subescapularis, capsule, and coracobraquialis muscles...

O presente trabalho analisa as principais técnicas cirúrgicas empregadas no tratamento da luxação recidivante do ombro (LRO), com o objetivo de obter a normalidade da amplitude dos movimentos articulares e associar diferentes tempos cirúrgicos num único procedimento para obter uma capacidade funcional completa, sem comprometer a normalidade dos movimentos, por causa das suturas tensas usadas nas cirurgias de Putti-Platt, Bankart, Latarjet, Dickson-O'Dell e outras. Após cuidadosa revisão desses métodos em uso, chegamos à conclusão de que a LRO pode ser considerada resolvida quanto à porcentagem de cura (97%). Permanecem, no entanto, limitações dos movimentos na grande maioria dos casos, aceitas até como necessárias para evitar recidivas. O nosso objetivo cirúrgico visa à obtenção de uma recuperação funcional completa, atuar simultaneamente sobre as várias lesões anatomopatológicas e abandonar a ideia das chamadas "lesões essenciais". A imobilização do ombro operado será feita somente durante a cicatrização das partes moles em rotação neutra. Com o uso de um enxerto ósseo pediculado dispensa-se qualquer tipo de imobilização prolongada, por causa da estabilidade obtida pela osteossíntese da coracoide no rebordo da glenoide, como na técnica de Latarjet. Essa nossa conduta, empregada desde 1959, consiste, portanto, na associação das várias técnicas com as quais se obtêm a cura sem limitação dos movimentos, por causa da redução da tensão nas suturas da cápsula e dos músculos subescapular e coracobraquial empregadas nas técnicas acima...

Concept of healing of recurrent shoulder dislocation.

This paper presents the main surgical techniques applied in the treatment of anterior recurrent shoulder dislocation, aiming the achievement of the normality of articulate movements. This was obtained by combining distinct surgical procedures, which allowed the recovery of a complete functional capacity of the shoulder, without jeopardizing the normality of movement, something that has not been recorded in the case of the tense sutures of the surgical procedures of Putti-Platt, Bankart, Latarjet, Dickson-O'Dell and others. The careful review of the methods applied supports the conclusion that recurrent shoulder dislocation can be cured, since cure has been obtained in 97% of the treated cases. However, some degree of limitation in the shoulder movement has been observed in most of the treated cases. Our main goal was to achieve a complete shoulder functional recovery, by treating simultaneously all of the anatomical-pathological lesions, without considering the so-called essential lesions. The period of post-operatory immobilization only last for the healing of soft parts; this takes place in a position of neutral shoulder rotation, since the use of vascular bone graft eliminates the need for long time immobilization, due to the shoulder stabilization provided by rigid fixation of the coracoid at the glenoid edge, as in the Latarjet's technique. Our procedure, used since 1959, comprises the association of several techniques, which has permitted shoulder healing without movement limitation. That was because of the tension reduction in the sutures of the subescapularis, capsule, and coracobraquialis muscles.

O presente trabalho analisa as principais técnicas cirúrgicas empregadas no tratamento da luxação recidivante do ombro (LRO), com o objetivo de obter a normalidade da amplitude dos movimentos articulares e associar diferentes tempos cirúrgicos num único procedimento para obter uma capacidade funcional completa, sem comprometer a normalidade dos movimentos, por causa das suturas tensas usadas nas cirurgias de Putti-Platt, Bankart, Latarjet, Dickson-O'Dell e outras.Após cuidadosa revisão desses métodos em uso, chegamos à conclusão de que a LRO pode ser considerada resolvida quanto à porcentagem de cura (97%). Permanecem, no entanto, limitações dos movimentos na grande maioria dos casos, aceitas até como necessárias para evitar recidivas.O nosso objetivo cirúrgico visa à obtenção de uma recuperação funcional completa, atuar simultaneamente sobre as várias lesões anatomopatológicas e abandonar a ideia das chamadas "lesões essenciais".A imobilização do ombro operado será feita somente durante a cicatrização das partes moles em rotação neutra. Com o uso de um enxerto ósseo pediculado dispensa-se qualquer tipo de imobilização prolongada, por causa da estabilidade obtida pela osteossíntese da coracoide no rebordo da glenoide, como na técnica de Latarjet.Essa nossa conduta, empregada desde 1959, consiste, portanto, na associação das várias técnicas com as quais se obtêm a cura sem limitação dos movimentos, por causa da redução da tensão nas suturas da cápsula e dos músculos subescapular e coracobraquial empregadas nas técnicas acima.

Tratamento cirúrgico das fraturas instáveis da coluna toracolombar / Surgical treatment of unstable fractures of thoracolumbar spine

O propósito deste trabalho é relatar o resultado encontrado em 12 pacientes com fratura instáveis da coluna toracolombar tratado com as técnicas de Harrington-Luque e Hartshill num período de quatro anos. Os autores concluem que a estabilidade alcançada pela instrumentaçao previne futuros danos neurais durante o período em que a fusao vertebral está ocorrendo e que o fator primordial de reduzir e fixar estas fraturas é promover a estabilidade; por isso, nao indicam a laminectomia isolada.

Fratura de Colles: fixaçäo com dois fios de Steinmann / Colle's fracture: fixation with 2 Steinmann wires

Oitenta e seis pacientes com fraturas desviadas de Colles foram tratados com reduçäo fechada e fixaçäo percutânea com dois fios de Steinmann. Näo foram constatadas complicaçöes sérias. No follow-up, constatou-se que 56 fraturas ficaram anatomicamente excelentes, 25 boas e três pobres. Do total, 16 punhos mudaram a graduaçäo anatômica e foram considerados como pobremente fixados ou eram fraturas cominutivas de alta energia. Clinicamente, um paciente teve infecçäo com significante perda de flexäo e extensäo; um paciente era portador de paralisia espástica. A técnica de imobilizaçäo foi considerada como de pouca importância no resultado final. É recomendado o uso de fixaçäo percutânea, com fios de Steinmann, em pessoas idosas com fraturas desviadas e cominutivas

Quadricepsplastia: tratamento da rigidez em extensäo do joelho / Quadricepsplasty: treatment of the rigidity of the knee in extension

Apresentam-se 19 casos de quadricepsplastia, sendo 6 operados por técnicas diversas e 13 operados pela técnica de Judet. A etiologia e a etiopatogenia da rigidez em extensäo do joelho säo revistas e a técnica de Judet é descrita detalhadamente. Os resultados säo comparados entre as diferentes técnicas, confirmando as estatísticas largamente favoráveis à técnica de Judet, näo só quanto à flexäo obtida, como pela ausência de complicaçöes comuns nas demais técnicas