This report seeks to describe the status of kidney disease and renal replacement therapy in lower-resource settings, particularly sub-Saharan Africa. Acute kidney injury and transplantation are included on a limited basis because it is impossible consider the renal replacement therapy landscape at the exclusion of either. As in the rest of the developing world, chronic kidney disease and end-stage renal disease place a sizable and rapidly growing burden on sub-Saharan Africa, and Africans face a double-burden of disease from communicable and non-communicable diseases. Meanwhile, renal replacement therapy and the subspecialty of nephrology are expanding in sub-Saharan Africa, from non-existence in many countries to a limited, tentative subsistence, largely with the support of international organizations and the dedication of local nephrologists. Hemodialysis is the most common form of renal replacement therapy in sub-Saharan Africa, but peritoneal dialysis services, particularly for acute kidney injury, are growing and renal transplants are performed in a few sub-Saharan countries. Nonetheless, in the majority of sub-Saharan Africa, maintenance dialysis is still only available to the wealthy urban few. Although peritoneal dialysis may seem more feasible in the developing world than hemodialysis for multiple reasons, it is still fraught with challenges that make widespread implementation presently unadvisable. As renal replacement therapy is costly and currently unaffordable on a large scale for most of these countries, emphasis must be on identifying at-risk populations through screening and low-cost treatment or management of risk factors to mitigate chronic kidney disease.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality. Considering its very poor prognosis, novel treatment options are urgently needed. MicroRNAs (miRNAs) are involved in the regulation of various physiological and pathological processes. In tumors, aberrant downregulation of given miRNAs may result in pathological overexpression of oncogenes, rendering miRNA replacement as a promising therapeutic strategy. In different tumor entities, miRNA-506-3p (miR506-3p) has been ambivalently described as tumor suppressing or oncogenic. In PDAC, miR-506 is mainly considered as a tumor-suppressing miRNA. In this study, we extensively analyze the cellular and molecular effects of miRNA-506-3p replacement in different PDAC cell lines. Beyond profound antiproliferation and induction of cell death and autophagy, we describe new cellular miR506-3p effects, i.e., induction of senescence and reactive oxygen species (ROS), as well as alterations in mitochondrial potential and structure, and identify multiple underlying molecular effects. In a preclinical therapy study, PDAC xenograft-bearing mice were treated with nanoparticle-formulated miRNA-506 mimics. Profound tumor inhibition upon systemic miRNA-506 administration was associated with multiple cellular and molecular effects. This demonstrates miRNA replacement as a potential therapeutic option for PDAC patients. Due to its broad mechanisms of action on multiple relevant target genes, miR506-3p is identified as a particularly powerful tumor-inhibitory miRNA.

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No / MicroRNAs are a relatively new class of small, noncoding RNA species that represent a cornerstone of cell biology, with diverse roles ranging from embryonic development to aging. miRNAs function to regulate posttranscriptional gene expression, are critical to the normal function of cells, and as such are frequently dysregulated during disease processes. In this chapter, we discuss the biogenesis and mechanism of action of miRNA and their role in cancer initiation, promotion, and progression. In addition, we discuss the most recently identified dual roles of miRNA in epigenetic gene regulation; how they are both regulators and regulated. Finally, we discuss the emerging roles of miRNA as epigenetic anti-cancer therapeutics, the current research examining inhibition of oncogenic miRNAs, and studies now establishing the potential of replacing lost, tumor-suppressive miRNA.

INTRODUÇÃO: A rigidez arterial é fator de risco cardiovascular pouco estudado e importante determinante de sobrecarga cardiovascular, estando associada ao envelhecimento. Analisou-se a ação das terapêuticas com estrogênios eqüinos conjugados (EEC) ou raloxifeno sobre os índices de rigidez, com o intuito de se observar a influência destas medicações na rigidez arterial, bem como se as mesmas são capazes de influenciar o envelhecimento vascular bem sucedido. MÉTODOS: Realizou-se estudo duplo cego, randomizado, placebo-controlado, que envolveu sessenta e sete mulheres saudáveis, normotensas e com 1 a 10 anos de menopausa, divididas em três grupos de 24, 25 e 18 mulheres. Estas receberam placebo, 0,625 mg EEC ou 60 mg de raloxifeno, respectivamente, 1 comprimido por dia, por 4 meses consecutivos. Analisou-se a rigidez arterial, através da avaliação das velocidades de onda de pulso carótida-femoral (VOP CF), fêmoro-pediosa (VOP FP), e do índice de amplificação (IA) da pressão sistólica na artéria carótida. RESULTADOS: Não se observou qualquer alteração dos índices de rigidez arterial associada às intervenções farmacológicas no grupo placebo (VOP CF pré x pós: 644 x 626 cm/s, p= 0,09; VOP FP pré x pós: 1006 x 1012 cm/s, p= 0,77; IA pré x pós = 30 x 29%, p= 0,55), no grupo EEC (VOP CF pré x pós: 642 x 600 cm/s, p= 0,11; VOP FP pré x pós: 952 x 971 cm/s, p= 0,66; IA pré x pós: 25 x 32%, p= 0,82) e no grupo raloxifeno (VOP CF pré x pós: 636 x 601 cm/s, p= 0,12; VOP FP pré x pós: 964 x 941 cm/s, p= 0,62; IA pré x pós:25 x 25%, p= 0,65). Apesar da ausência de ação das drogas sobre a rigidez arterial, houve uma correlação significativa entre o grau de rigidez arterial basal e a resposta à intervenção farmacológica, particularmente no grupo EEC, de tal maneira que a redução dos índices de rigidez neste grupo foi proporcional ao nível de rigidez basal, apresentando as seguintes relações: VOP CF (r= -0,602, p= 0,001); VOP FP (r= -0,455, p= 0,022); IA (r= -0,410, p= 0,042). CONCLUSÃO: EEC e raloxifeno não parecem afetar a rigidez arterial de mulheres sadias e normotensas com menos de 10 anos de menopausa / INTRODUCTION: Arterial stiffness has been recognized as a cardiovascular risk factor, an important determinant of the left ventricular overload and a marker of cardiovascular aging. However, the clinical impact of arterial stiffness and how it is affected by hormone therapy has not been fully investigated. This study analyzed the influence of conjugated equine estrogens (CEE) or raloxifene on arterial stiffness and how the may influence successful cardiovascular aging. METHODS: Sixty-seven healthy and normotensive women with 1 to 10 years of menopause were randomly assigned to one of three groups, with 24, 25, and 18 participants. They were given oral placebo, 0,625 mg of conjugated equine estrogen, or 60 mg of raloxifene, respectively, for 4 consecutive months. Arterial stiffness was evaluated by measurement of the carotid-femoral pulse wave velocity (PWV CF) and femoral-dorsalis pedis pulse wave velocity (PWV FP), and the systolic pressure augmentation index (AI) at the carotid artery obtained by applanation tonometry. RESULTS: None of the treatment regimens affected arterial stiffness: placebo (PWV CF before x after: 644 x 626 cm/s, p= 0.09; PWV FP before x after : 1006 x 1012 cm/s, p= 0.77; AI before x after = 30 x 29%, p= 0.55), CEE (PWV CF before x after: 642 x 600 cm/s, p= 0.11; PWV FP before x after: 952 x 971 cm/s, p= 0.66; AI before x after: 25 x 32%, p= 0.82) and raloxifene (PWV CF before x after: 636 x 601 cm/s, p= 0.12; PWV FP before x after: 964 x 941 cm/s, p= 0.62; AI before x afer:25 x 25%, p= 0.65). Despite the absence of statistically significant reduction in arterial stiffness with treatment, there was a significant correlation between basal stiffness and the degree of reduction in the indexes measured, indicating that the higher the basal stiffness, the greater the degree of reduction, particularly in the CEE group: PWV CF (r= -0.602, p= 0.001); PWV FP (r= -0.455, p= 0.022); AI (r= -0.410, p= 0.042). CONCLUSIONS: Conjugated equine estrogen and raloxifene do not seem to affect arterial stiffness of healthy normotensive women with less than 10 years of menopause

INTRODUÇÃO: A rigidez arterial é fator de risco cardiovascular pouco estudado e importante determinante de sobrecarga cardiovascular, estando associada ao envelhecimento. Analisou-se a ação das terapêuticas com estrogênios eqüinos conjugados (EEC) ou raloxifeno sobre os índices de rigidez, com o intuito de se observar a influência destas medicações na rigidez arterial, bem como se as mesmas são capazes de influenciar o envelhecimento vascular bem sucedido. MÉTODOS: Realizou-se estudo duplo cego, randomizado, placebo-controlado, que envolveu sessenta e sete mulheres saudáveis, normotensas e com 1 a 10 anos de menopausa, divididas em três grupos de 24, 25 e 18 mulheres. Estas receberam placebo, 0,625 mg EEC ou 60 mg de raloxifeno, respectivamente, 1 comprimido por dia, por 4 meses consecutivos. Analisou-se a rigidez arterial, através da avaliação das velocidades de onda de pulso carótida-femoral (VOP CF), fêmoro-pediosa (VOP FP), e do índice de amplificação (IA) da pressão sistólica na artéria carótida. RESULTADOS: Não se observou qualquer alteração dos índices de rigidez arterial associada às intervenções farmacológicas no grupo placebo (VOP CF pré x pós: 644 x 626 cm/s, p= 0,09; VOP FP pré x pós: 1006 x 1012 cm/s, p= 0,77; IA pré x pós = 30 x 29%, p= 0,55), no grupo EEC (VOP CF pré x pós: 642 x 600 cm/s, p= 0,11; VOP FP pré x pós: 952 x 971 cm/s, p= 0,66; IA pré x pós: 25 x 32%, p= 0,82) e no grupo raloxifeno (VOP CF pré x pós: 636 x 601 cm/s, p= 0,12; VOP FP pré x pós: 964 x 941 cm/s, p= 0,62; IA pré x pós:25 x 25%, p= 0,65). Apesar da ausência de ação das drogas sobre a rigidez arterial, houve uma correlação significativa entre o grau de rigidez arterial basal e a resposta à intervenção farmacológica, particularmente no grupo EEC, de tal maneira que a redução dos índices de rigidez neste grupo foi proporcional ao nível de rigidez basal, apresentando as seguintes relações: VOP CF (r= -0,602, p= 0,001); VOP FP (r= -0,455, p= 0,022); IA (r= -0,410, p= 0,042). CONCLUSÃO: EEC e raloxifeno não parecem afetar a rigidez arterial de mulheres sadias e normotensas com menos de 10 anos de menopausa / INTRODUCTION: Arterial stiffness has been recognized as a cardiovascular risk factor, an important determinant of the left ventricular overload and a marker of cardiovascular aging. However, the clinical impact of arterial stiffness and how it is affected by hormone therapy has not been fully investigated. This study analyzed the influence of conjugated equine estrogens (CEE) or raloxifene on arterial stiffness and how the may influence successful cardiovascular aging. METHODS: Sixty-seven healthy and normotensive women with 1 to 10 years of menopause were randomly assigned to one of three groups, with 24, 25, and 18 participants. They were given oral placebo, 0,625 mg of conjugated equine estrogen, or 60 mg of raloxifene, respectively, for 4 consecutive months. Arterial stiffness was evaluated by measurement of the carotid-femoral pulse wave velocity (PWV CF) and femoral-dorsalis pedis pulse wave velocity (PWV FP), and the systolic pressure augmentation index (AI) at the carotid artery obtained by applanation tonometry. RESULTS: None of the treatment regimens affected arterial stiffness: placebo (PWV CF before x after: 644 x 626 cm/s, p= 0.09; PWV FP before x after : 1006 x 1012 cm/s, p= 0.77; AI before x after = 30 x 29%, p= 0.55), CEE (PWV CF before x after: 642 x 600 cm/s, p= 0.11; PWV FP before x after: 952 x 971 cm/s, p= 0.66; AI before x after: 25 x 32%, p= 0.82) and raloxifene (PWV CF before x after: 636 x 601 cm/s, p= 0.12; PWV FP before x after: 964 x 941 cm/s, p= 0.62; AI before x afer:25 x 25%, p= 0.65). Despite the absence of statistically significant reduction in arterial stiffness with treatment, there was a significant correlation between basal stiffness and the degree of reduction in the indexes measured, indicating that the higher the basal stiffness, the greater the degree of reduction, particularly in the CEE group: PWV CF (r= -0.602, p= 0.001); PWV FP (r= -0.455, p= 0.022); AI (r= -0.410, p= 0.042). CONCLUSIONS: Conjugated equine estrogen and raloxifene do not seem to affect arterial stiffness of healthy normotensive women with less than 10 years of menopause

No description available.