GH/IGF-1 Abnormalities and Muscle Impairment : from basic research to clinical practice

The impairment of skeletal muscle function is one of the most debilitating least understood co-morbidity that accompanies acromegaly (ACRO). Despite being one of the major determinants of these patients' poor quality of life, there is limited evidence related to the underlying mechanisms and treatment options. Although growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels are associated, albeit not indisputable, with the presence and severity of ACRO myopathies the precise effects attributed to increased GH or IGF-1 levels are still unclear. Yet, cell lines and animal models can help us bridge these gaps. This review aims to describe the evidence regarding the role of GH and IGF-1 in muscle anabolism, from the basic to the clinical setting with special emphasis on ACRO. We also pinpoint future perspectives and research lines that should be considered for improving our knowledge in the field

Pituitary Apoplexy: Risk Factors and Underlying Molecular Mechanisms

Apoplexy; Growth factors; Matrix metalloproteinaseApoplejía; Factores de crecimiento; Metaloproteinasa de la matrizApoplexia; Factors de creixement; Metaloproteinasa de la matriuPituitary apoplexy is a rare syndrome, graded from asymptomatic subclinical apoplexy to a life-threatening condition due to pituitary ischemia or haemorrhage of an enlarged pituitary gland. The risk factors and the molecular underlying mechanisms are yet to be elucidated. We provide an overview of the general concepts, the potential factors associated with pituitary adenoma susceptibility for apoplectic events and the molecular mechanisms that could be involved such as HIF-1α/VEGF pathways and metalloproteinases activation, among others. The knowledge of the molecular mechanisms that could participate in the pathogenesis of pituitary apoplexy is crucial to advancement in the identification of future diagnostic tools and therapeutic targets in this rare but sometimes fatal condition

What else can we do to prevent diabetic retinopathy?

Diabetic retinopathy; Modifiable risk factors; Neurovascular unitRetinopatía diabética; Factores de riesgo modificables; Unidad neurovascularRetinopatia diabètica; Factors de risc modificables; Unitat neurovascularThe classical modifiable factors associated with the onset and progression of diabetic retinopathy are the suboptimal control of blood glucose levels and hypertension, as well as dyslipidaemia. However, there are other less recognised modifiable factors that can play a relevant role, such as the presence of obesity or the abnormal distribution of adipose tissue, and others related to lifestyle such as the type of diet, vitamin intake, exercise, smoking and sunlight exposure. In this article we revisit the prevention of diabetic retinopathy based on modulating the modifiable risk factors, as well as commenting on the potential impact of glucose-lowering drugs on the condition. The emerging concept that neurodegeneration is an early event in the development of diabetic retinopathy points to neuroprotection as a potential therapeutic strategy to prevent the advanced stages of the disease. In this regard, the better phenotyping of very early stages of diabetic retinopathy and the opportunity of arresting its progression using treatments targeting the neurovascular unit (NVU) are discussed.Open Access Funding provided by Universitat Autonoma de Barcelona

Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications

Dopamine; Lactotroph tumour; ProlactinomaDopamina; Tumor lactòtrof; ProlactinomaDopamina; Tumor lactotrofo; ProlactinomaProlactinoma has the highest incidence rate among patients with functional pituitary tumours. Although mostly benign, there is a subgroup that can be aggressive. Some clinical, radiological and pathology features have been associated with a poor prognostic. Therefore, it can be considered as a group of heterogeneous tumours. The aim of this paper is to give an overview of the molecular pathways involved in the behaviour of prolactinoma in order to improve our approach and gain deeper insight into the better understanding of tumour development and its management. This is essential for identifying patients harbouring aggressive prolactinoma and to establish personalised therapeutics options.This research received no external funding

New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes

Dementia; Retinal microperimetry; Type 2 diabetesDemencia; Microperimetría retiniana; Diabetes tipo 2Demència; Microperimetria retiniana; Diabetis tipus 2The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a “window” to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry

Watchdog or Lapdog: Limits of African Media Coverage of the Extractive Sector

The purpose of this study is to evaluate the quality of African media coverage of the extractive industries. This sector plays prominently on the African political, economic, social and journalistic landscape, yet coverage of these industries remains a challenge for African journalists. The financial and technical aspects of the extractive sector are complex, and both governments and companies often have a vested interest in withholding information from journalists. Many reporters lack sufficient training, resources and/or journalistic freedom to publish accurate, well‐researched, in‐depth coverage. As a result, what are arguably some of the most critical industries on the continent operate in relative freedom from public scrutiny. By making a careful study of African media coverage of the extractive sector in three countries, this report hopes to identify key strengths and weaknesses in extractive industry reporting as well as opportunities for media support and the expansion or revision of current media training efforts. The discovery of oil in Uganda in 2006 and in Ghana in 2007 brought both a great deal of excitement and a considerable level of worry to these countries. While extractive resources (oil, gas and mining) are a leading source of wealth for many African countries, this wealth often leads to corruption and conflict. In fact, countries with abundant natural resources tend to fall below less resource‐wealthy countries in terms of human development, a paradox economist Richard Auty and subsequent researchers have labeled the "resource curse." This report is based on two premises: first, that if Africans are to benefit from the immense resource stores that lie beneath their soil, great efforts must be made toward transparency in how these resources are handled. Second, the call for transparency cannot come from non‐governmental organizations and individual political leaders alone. The African media have a critical responsibility to push toward government and corporate openness in the extractive industries. African media have made great strides since the latter half of the twentieth century, but they continue to struggle to fulfill their role as society's watchdog. Instead of keeping governments in check through enterprising stories or investigative pieces, most African media have instead been leashed by a confluence of factors. Lack of resources, government intimidation and interference, media ownership, revenue structures and declining educational quality all make the job of the African journalist difficult. To mitigate some of these constraints, local and international non‐governmental organizations (NGOs), media outlets and in some cases government agencies are training journalists to more fully understand the intricacies of the areas that they cover

What else can we do to prevent diabetic retinopathy?

The classical modifiable factors associated with the onset and progression of diabetic retinopathy are the suboptimal control of blood glucose levels and hypertension, as well as dyslipidaemia. However, there are other less recognised modifiable factors that can play a relevant role, such as the presence of obesity or the abnormal distribution of adipose tissue, and others related to lifestyle such as the type of diet, vitamin intake, exercise, smoking and sunlight exposure. In this article we revisit the prevention of diabetic retinopathy based on modulating the modifiable risk factors, as well as commenting on the potential impact of glucose-lowering drugs on the condition. The emerging concept that neurodegeneration is an early event in the development of diabetic retinopathy points to neuroprotection as a potential therapeutic strategy to prevent the advanced stages of the disease. In this regard, the better phenotyping of very early stages of diabetic retinopathy and the opportunity of arresting its progression using treatments targeting the neurovascular unit (NVU) are discussed

New methods for the diagnosis and monitoring of cognitive function in patients with type 2 diabetes

The presence of type 2 diabetes acts as an accelerator of cognitive impairment (mild cognitive impairment and later dementia), with a significant impact on the management of the disease and its complications. Therefore, it is recommended to perform an annual evaluation of cognitive function in patients with diabetes older than 65 years. Current guidelines still recommend the use of the Minimental State Evaluation Test (MMSE) as screening test, but it has a modest sensitivity and specificity for identifying mild cognitive impairment. This represents an important gap because patients with mild cognitive impairment are at risk of progressing to dementia. The neurocognitive diagnosis is based on complex neuropsychological tests, which require specifically trained personnel and are time consuming, making its routine incorporation into daily clinical practice unfeasible. Therefore, at present there are no reliable biomarkers to identify patients with type 2 diabetes at increased risk of developing cognitive impairment. Since the brain and the retina have a common embryological origin, our Research Group, has worked over the last 10 years evaluating the usefulness of the retina as a "window" to the brain. We provided evidence that retinal microperimetry is a simple, feasible and useful tool for screening and monitoring cognitive function in patients with type 2 diabetes. We propose a review of actual tests recommended for screening of cognitive impairment as well as an update of new emerging methods, such as retinal microperimetry

Factors angiogènics en la retinopatia diabètica proliferativa

La retinopatia diabètica és la causa principal de ceguesa en els individus en edat laboral. Entre les primeres troballes histològiques, tenim el dany neuroretinià, l'engruiximent de la membrana basal dels capill. ars i la pèrdua dels pericits i de les cèll. ules endotelials. La neovascularització, punt clau en la retinopatia diabètica proliferativa (PDR), succeeix en els estadis avançats i és la causa principal de ceguesa en la diabetis tipus 1. L'edema macular és una altra complicació de la diabetis i que és responsable principal de la pèrdua de visió, principalment en els casos de diabetis tipus 2. L'extravasació del contingut vascular, com a conseqüència del trencament de la barrera hematoretinal, és el fet principal present en la seva patogènesi. Llevat dels controls repetits de glucèmia i de tensió arterial, el tractament per fotocoagulació per làser és l'única eina útil contra la progressió de la retinopatia diabètica. Per tant, diversos nous tractaments farmacològics, basats en la comprensió dels mecanismes patofisiològics de la retinopatia diabètica, han estat desenvolupats en els darrers anys. Hi ha una creixent evidència que suggereix que diversos factors angiogènics duen a terme una funció crucial en el desenvolupament de la PDR. Entre aquests, el factor de creixement endotelial vascular (VEGF) és el més rellevant. Altres factors de creixement o citocines, com són el factor de creixement semblant a la insulina de tipus i (IGF-I), el factor de creixement del hepatòcits (HGF), el factor de creixement bàsic dels fibroblasts (b-FGF), el factor de creixement derivat de les plaquetes (PDGF), les citocines proinflamatòries i les angiopoetines, també estan implicats en la patogènesi de la PDR.Diabetic retinopathy is the leading cause of legal blindness among working-aged individuals. Neuroretinal damage, thickening of the capillary basement membrane and a loss of pericytes and endothelial cells are among the earliest histological features. Neovascularization, the hallmark of proliferative diabetic retinopathy (PDR), occurs in the advanced stages and is the main cause of blindness in type 1 diabetes. Macular edema is another retinal complication of diabetes that is responsible for a major part of vision loss, particularly in type 2 diabetes. Vascular leakage, as a consequence of a breakdown in the blood retinal barrier, is the main event involved in its pathogenesis. Apart from controlling blood glucose and blood pressure, laser photocoagulation treatment is the only tool in the current armamentarium against diabetic retinopathy progression. Therefore, new pharmacological treatments, based on an understanding of the patho-physiological mechanisms of diabetic retinopathy, have been developed in recent years. There is mounting evidence to suggest that angiogenic factors play a crucial role in PDR development, with vascular endothelial growth factor (VEGF) being the most relevant. Other growth factors or cytokines, such as insulin-like growth factor I (IGF-1), hepatocyte growth factor (HGF), basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), pro-inflammatory cytokines and angiopoietins, are also involved in the pathogenesis of PDR