Allogeneic mitochondrial transplantation ameliorates cardiac dysfunction due to doxorubicin: An in vivo study.

Damage to the mitochondria may lead to serious conditions that are difficult to treat. Doxorubicin is one of the most widely used chemotherapeutic drugs for the treatment of malignancies in children and adults, and reportedly causes damage to the mitochondria. Unfortunately, the dangerous cardiac side effects of doxorubicin appear when the patient is in the midst of a vigorous fight against the disease, either by taking doxorubicin alone or in combination with other drugs. This study aimed to determine whether exogenous healthy and functional mitochondria are internalized by cells, can it help the survival of these cells, and can reduce cardiotoxicity. For this purpose, isolated, pure, and functional exogenous mitochondria were injected into the tail vein of a rat model of doxorubicin-induced cardiotoxicity. After that, the heart function of the rats and their antioxidant status, inflammatory markers, and histopathological examination were investigated. Our findings show that intravenous mitochondrial transplantation provided efficient mitochondrial uptake and reduced cardiotoxicity by reducing ROS production, lipid peroxidation, and inflammation. In addition, the levels of ATP and antioxidant enzymes increased after mitochondrial transplantation; therefore all of these complex processes resulted in the reduction of apoptosis and necrosis in rat heart tissue. These promising results open the way to more effective cancer treatment without the side effects of related drugs. Transplanting exogenous mitochondria probably enhances the cell's mitochondrial network, potentially treating mitochondria-related disorders such as cardiovascular and neurodegenerative diseases, although the exact relationship between mitochondrial damage and these conditions remains unclear.

Mitotherapy in doxorubicin induced cardiotoxicity: A promising strategy to reduce the complications of treatment.

AIMS: Doxorubicin is a potent and broad-spectrum antineoplastic medication prescribed for both solid and hematological malignancies. Despite its value, the clinical use of doxorubicin is limited due to cardio-oncologic complication and cardiotoxic adverse effect. Among the mechanisms proposed for its toxicity, mitochondrial dysfunction has gained more attention. Therefore, if damaged mitochondria are replaced by normal efficient mitochondria, cardiac toxicity is expected to be reduced or improved. In this way, we have studied the efficiency of transplantation of freshly isolated rat liver mitochondria in neonatal rat cardiomyocytes that have been damaged by doxorubicin. MATERIALS AND METHODS: For this purpose, isolated mitochondria were characterized using mitochondrial complex II, membrane potential and swelling evaluations, and also fluorescence and electron microscopy. Afterward, the effect of mitotherapy on the damaged cardiomyocytes was investigated by using annexin V/PI staining, MTT, ROS, MMP, lipid peroxidation, GSH and ATP evaluations. KEY FINDINGS AND SIGNIFICANCE: Transplanted mitochondria could remarkably enter the neonatal rat cardiomyocytes. Addition of mitochondria to the damaged cardiomyocytes, significantly increased cell viability by reducing the level of reactive oxygen species and lipid peroxidation, increasing of ∆Ψ, ATP and GSH contents and decreasing of apoptotic and necrotic cell death. Our results showed that mitotherapy has a significant restorative effect on cardiotoxicity induced by doxorubicin, which promises a better future to reduce the complications of cancer treatment.

Comparison of 4 different techniques in first metatarsophalangeal joint arthrodesis.

AIMS: The aim of this study was to evaluate outcomes and fusion rates of 4 different methods of first metatarsophalangeal joint (MTPJ) arthrodesis. METHODS: We performed a retrospective analysis of first MTPJ fusion using Bold® and Acutrak® compression screws, universal 1/3 tubular plate and Hallu®-S non-locking plate in 6 hospitals in Dublin over 4 years. A cohort of 300 patients (351 feet) was operated on by 3 feet and ankle fellowship trained orthopaedic surgeons (PK, MMS, JVMcK) over 4 years. Mean age was 62.4 years. There were 261 females and 39 males. One hundred three patients had a fusion of first MTPJ using two Acutrak® screws and 90 with two Bold® screws. Sixty-five were fused with the Hallu-S® plate and 42 with the universal 1/3 tubular plate. Patients were evaluated clinically and radiographically at 6 weeks, 3 months and 12 months. RESULTS: Functional outcome scores performed using Manchester-Oxford Foot Questionnaire (MOXFQ). Failure rate in those fused with the Hallu®-S plate was 0%, Acutrak® screws 2.4%, Bold® screws 9.5% and universal 1/3 tubular plate 12.5% (p > 0.12). All treatment groups demonstrated significantly reduced MOXFQ scores (p value < 0.05). CONCLUSION: In this retrospective study for first MTPJ fusion, a low profile, pre-contoured plate in combination with a screw mode had the best results with no failure rates and improved MOXFQ scores. LEVEL OF CLINICAL EVIDENCE: IV, retrospective study.

Talonavicular synostosis with lateral ankle instability--A case report and review of the literature.

Talonavicular coalition is a rare autosomal recessive congenital anomaly that is usually asymptomatic and detected incidentally on radiographs. It is associated with symphalangism, clinodactyly, a great toe that is shorter than the second toe, clubfoot, calcaneonavicular coalition, talocalcaneal coalition and a ball-and-socket ankle joint. The authors present a review of the literature and case report of a patient with complete osseous talonavicular coalition, talocalcaneal coalition and lateral ankle instability which was successfully treated with subtalar fusion and lateral ligament reconstruction.