a-model-of-free-tissue-transfer-the-rat-epigastric-free-flap

A Model of Free Tissue Transfer: The Rat Epigastric Free Flap

Free tissue transfer has been increasingly used in clinical practice since the 1970s, allowing reconstruction of complex and otherwise untreatable defects ...

functional-physiological-methods-evaluating-median-nerve-regeneration

Functional and Physiological Methods of Evaluating Median Nerve Regeneration in the Rat

The main goal of this investigation is to show how to create and repair different types of median nerve (MN) lesions in the rat. Moreover, different ...

Centro Hospitalar de Lisboa Central – Hospital de São José

Centro Hospitalar de Lisboa Central

We have previously shown that acetic acid activates a mitochondria-dependent death process in Saccharomyces cerevisiae and that the ADP/ATP carrier (AAC) is required for mitochondrial outer membrane permeabilization and cytochrome c release. Mitochondrial fragmentation and degradation have also been shown in response to this death stimulus. Herein, we show that autophagy is not active in cells undergoing acetic acid-induced apoptosis and is therefore not responsible for mitochondrial degradation. Furthermore, we found that the vacuolar protease Pep4p and the AAC proteins have a role in mitochondrial degradation using yeast genetic approaches. Depletion and overexpression of Pep4p, an orthologue of human cathepsin D, delays and enhances mitochondrial degradation respectively. Moreover, Pep4p is released from the vacuole into the cytosol in response to acetic acid treatment. AAC-deleted cells also show a decrease in mitochondrial degradation in response to acetic acid and are not defective in Pep4p release. Therefore, AAC proteins seem to affect mitochondrial degradation at a step subsequent to Pep4p release, possibly triggering degradation through their involvement in mitochondrial permeabilization. The finding that both mitochondrial AAC proteins and the vacuolar Pep4p interfere with mitochondrial degradation suggests a complex regulation and interplay between mitochondria and the vacuole in yeast programmed cell death.

Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP/ATP carrier.

This study explored the effectiveness of psychoeducational programme for informal caregivers called 'Caring at home'.

Effectiveness of a psychoeducational programme for informal caregivers of older adults.

Thyroid cancer (TC) is frequently associated with BRAF or RAS oncogenic mutations and RET/PTC rearrangements, with aberrant RAF-MEK-ERK and/or PI3K pathway activation. BRAF underlies ERK activation in most TC cells, but not in TPC-1 cells with RET/PTC1 rearrangement. Here, we show that depletion of RAF-1, a RAF family member with a poorly defined role in TC, decreases proliferation and increases apoptosis in TPC-1 cells and, less significantly, in cells harboring a BRAF(V600E) or HRAS(G13R) mutations, but without affecting ERK activation. We further demonstrate that constitutive activation of ERKs in TPC-1 cells is not caused by mutations in 50 oncogenes and tumor suppressors prone to activate the ERK pathway, or affected by inhibition of BRAF, MEK1/2 or PI3K. Our data indicate that RAF-1 is important for the survival of TPC-1 cells independently of the classical MEK1/2-ERK activation, offering new perspectives on RET/PTC signaling and for the therapy of thyroid cancers.

RAF-1 promotes survival of thyroid cancer cells harboring RET/PTC1 rearrangement independently of ERK activation.

The recent interest to modulate autophagy in cancer therapy has been hampered by the dual roles of this conserved catabolic process in cancer, highlighting the need for tailored approaches. Since RAS isoforms have been implicated in autophagy regulation and mutation of the KRAS oncogene is highly frequent in colorectal cancer (CRC), we questioned whether/how mutant KRAS alleles regulate autophagy in CRC and its implications. We established two original models, KRAS-humanized yeast and KRAS-non-cancer colon cells and showed that expression of mutated KRAS up-regulates starvation-induced autophagy in both. Accordingly, KRAS down-regulation inhibited autophagy in CRC-derived cells harboring KRAS mutations. We further show that KRAS-induced autophagy proceeds via up-regulation of the MEK/ERK pathway in both colon models and that KRAS and autophagy contribute to CRC cell survival during starvation. Since KRAS inhibitors have proven difficult to develop, our results suggest using autophagy inhibitors as a combined/alternative therapeutic approach in CRCs with mutant KRAS.

Colorectal cancer-related mutant KRAS alleles function as positive regulators of autophagy.

In the face of limited resources and an aging population with increasingly care needs, healthcare systems must identify community-dwelling older adults with mental health problems at higher risk of adverse outcomes such as institutionalization, hospitalization and death, in order to deliver timely and efficient care. The objectives of this study were to assess the prevalence of mental health concerns and the associated perceived risk of adverse outcomes in a large sample of older patients in primary care (PC). We trained general practitioners and nurses to use the Risk Instrument for Screening in the Community to rank perceived risk of mental health concerns (including neurocognitive and mood disorders) from 1 (mild) to 3 (severe). The mean age of the 4499 people assessed was 76.3 years (SD = 7.3) and 2645 (58.8%) were female. According to the PC team 1616 (35.9%) were perceived to have mental health concerns of whom 847 (52.4%) were mild, 559 (34.6%) were moderate and 210 (13%) were severe. Patients with mental health concerns had higher odds of perceived risk of adverse outcomes (OR = 2.22, 95% CI 1.83-2.69 for institutionalization; OR = 1.66, 95% CI 1.41-1.94 for hospitalization; OR = 1.69, 95% CI 1.42-2.01 for death). These results suggest a high prevalence of mental health concerns among older adults and supports the need for early identification of patients at high-risk of adverse healthcare outcomes.

Perceived Risk of Mental Health Problems in Primary Care.

The idiopathic inflammatory myopathies are uncommon and heterogeneous disorders. Their classification is based on distinct clinicopathologic features. Although idiopathic inflammatory myopathies share some similarities, different subtypes may have variable responses to therapy, so it is very important to distinguish the correct subtype. There are few randomised, double blind placebo controlled studies to support the current treatment. High dose corticosteroids continue to be the first-line therapy and other immunosupressive drugs are used in refractory cases, as well as steroid-sparing agents. Some novel therapeutic approaches have emerged as potential treatment including tacrolimus, intravenous immunoglobulin and rituximab, following good outcomes reported in case studies. However, more randomised controlled trials are needed. This review considers the current and the potential future therapies for inflammatory myopathies.

Current pharmacological treatment of idiopathic inflammatory myopathies.

Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis.

Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis.

There is a large gap between life expectancy and healthy life years at age 65. To reduce this gap, it is necessary that people with medical concerns perceived at higher risk of adverse outcomes are readily identified and treated. The same goes for the need to implement prevention plans. The main objectives of this study are to, in a first step, (a) estimate the percentage of medical concerns, (b) identify factors associated with this concern; in a second step, (c) estimate the perceived risk of death, and (d) evaluate the ability of medical concerns to predict this risk. Results show that the existence and severity of medical concerns are crucial in the prediction of perceived risk of death. Early identification of severity of medical concerns and the availability and adequacy of informal caregiving should allow healthcare professionals to promptly initiate an appropriate assessment and treatment of older patients.

Perceived Risk of Death in Older Primary Care Patients.

Although numerous experimental models of arterialized venous flaps (AVFs) have been proposed, no single model has gained widespread acceptance. The main aim of this work was to evaluate the survival area of AVFs produced with different vascular constructs in the abdomen of the rat.

Optimization of an Arterialized Venous Fasciocutaneous Flap in the Abdomen of the Rat.

Many fundamental questions regarding the blood supply to the integument of the rat remain to be clarified, namely the degree of homology between rat and humans. The aim of this work was to characterize in detail the macro and microvascular blood supply to the integument covering the ventrolateral aspect of the abdominal wall of the rat.

Blood Supply to the Integument of the Abdomen of the Rat: A Surgical Perspective.

The aim of this study was to evaluate in the Wistar rat the efficacy of various autologous nerve conduits with various forms of blood supply in reconstructing a 10-mm-long gap in the median nerve (MN) under conditions of local ischemia. A 10-mm-long median nerve defect was created in the right arm. A loose silicone tube was placed around the nerve gap zone, in order to simulate a local ischemic environment. Rats were divided in the following experimental groups (each with 20 rats): the nerve Graft (NG) group, in which the excised MN segment was reattached; the conventional nerve flap (CNF) and the arterialized neurovenous flap (ANVF) groups in which the gap was bridged with homonymous median nerve flaps; the prefabricated nerve flap (PNF) group in which the gap was reconstructed with a fabricated flap created by leaving an arteriovenous fistula in contact with the sciatic nerve for 5 weeks; and the two control groups, Sham and Excision groups. In the latter group, the proximal stump of the MN nerve was ligated and no repair was performed. The rats were followed for 100 days. During this time, they did physiotherapy. Functional, electroneuromyographic and histological studies were performed. The CNF and ANVF groups presented better results than the NG group in the following assessments: grasping test, nociception, motor stimulation threshold, muscle weight, and histomorphometric evaluation. Radial deviation of the operated forepaw was more common in rats that presented worse results in the other outcome variables. Overall, CNFs and ANVFs produced a faster and more complete recovery than NGs in the reconstruction of a 10-mm-long median nerve gap in an ischemic environment in the Wistar rat. Although, results obtained with CNFs were in most cases were better than ANVFs, these differences were not statistically significant for most of the outcome variables.

Reconstruction of a 10-mm-long median nerve gap in an ischemic environment using autologous conduits with different patterns of blood supply: A comparative study in the rat.

The main aim of this work was to study the usefulness of human β-defensins 2 (BD-2) and 3 (BD-3), which are part of the innate immune system, in the treatment of infected ischemic skin flaps. We investigated the effect of transducing rat ischemic skin flaps with lentiviral vectors encoding human BD-2, BD-3, or both BD-2 and BD-3, to increase flap survival in the context of a P. aeruginosa infection associated with a foreign body. The secondary endpoints assessed were: bacterial counts, and biofilm formation on the surface of the foreign body. A local ischemic environment was created by producing arterialized venous flaps in the left epigastric region of rats. Flaps were intentionally infected by placing underneath them two catheters with 10 CFU of P. aeruginosa before the surgical wounds were hermetically closed. Flap biopsies were performed 3 and 7 days post-operatively, and the specimens submitted to immunohistochemical analysis for BD-2 and BD-3, as well as to bacterial quantification. Subsequently, the catheter segments were analyzed with scanning electron microscopy (SEM). Flaps transduced with BD-2 and BD-3 showed expression of these defensins and presented increased flap survival. Rats transduced with BD-3 presented a net reduction in the number of P. aeruginosa on the surface of the foreign body and lesser biofilm formation.

ArticleTotal : 2	Year
Publication title Cited by 22	2017
Publication title Cited by 15	2020

Article	Year
Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP/ATP carrier. Molecular microbiology\| PubMed ID: 20345665	2010
Effectiveness of a psychoeducational programme for informal caregivers of older adults. Scandinavian journal of caring sciences\| PubMed ID: 25856726	2016
RAF-1 promotes survival of thyroid cancer cells harboring RET/PTC1 rearrangement independently of ERK activation. Molecular and cellular endocrinology\| PubMed ID: 26265449	2015
Colorectal cancer-related mutant KRAS alleles function as positive regulators of autophagy. Oncotarget\| PubMed ID: 26418750	2015
Perceived Risk of Mental Health Problems in Primary Care. Frontiers in aging neuroscience\| PubMed ID: 26635600	2015
Current pharmacological treatment of idiopathic inflammatory myopathies. Expert review of clinical pharmacology\| PubMed ID: 26708717	2016
Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis. BMC cancer\| PubMed ID: 27460659	2016
Perceived Risk of Death in Older Primary Care Patients. International journal of aging & human development\| PubMed ID: 27655954	2016
Optimization of an Arterialized Venous Fasciocutaneous Flap in the Abdomen of the Rat. Plastic and reconstructive surgery. Global open\| PubMed ID: 28894657	2017
Blood Supply to the Integument of the Abdomen of the Rat: A Surgical Perspective. Plastic and reconstructive surgery. Global open\| PubMed ID: 29062636	2017
Reconstruction of a 10-mm-long median nerve gap in an ischemic environment using autologous conduits with different patterns of blood supply: A comparative study in the rat. PloS one\| PubMed ID: 29659600	2018
BD-2 and BD-3 increase skin flap survival in a model of ischemia and Pseudomonas aeruginosa infection. Scientific reports\| PubMed ID: 31133641	2019

Sara Alves

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