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The past two decades have witnessed an explosion of research on the molecular mechanisms of autophagy and its roles in physiology and disease. Numerous gene products essential for the induction [...], Defects in autophagy have been linked to a wide range of medical illnesses, including cancer as well as infectious, neurodegenerative, inflammatory, and metabolic diseases. These observations have led to the hypothesis that autophagy inducers may prevent or treat certain clinical conditions. Lifestyle and nutritional factors, such as exercise and caloric restriction, may exert their known health benefits through the autophagy pathway. Several currently available FDA- approved drugs have been shown to enhance autophagy, and this autophagy-enhancing action may be repurposed for use in novel clinical indications. The development of new drugs that are designed to be more selective inducers of autophagy function in target organs is expected to maximize clinical benefits while minimizing toxicity. This Review summarizes the rationale and current approaches for developing autophagy inducers in medicine, the factors to be considered in defining disease targets for such therapy, and the potential benefits of such treatment for human health.

Introduction Autophagy is a major intracellular catabolic mechanism that directs selected cytoplasmic components and organelles to the lysosome for degradation. Macroautophagy (hereafter referred to as 'autophagy') is responsible for the [...], Autophagy is an important intracellular catabolic mechanism critically involved in regulating tissue homeostasis. The implication of autophagy in human diseases and the need to understand its regulatory mechanisms in mammalian cells have stimulated research efforts that led to the development of high-throughput screening protocols and small-molecule modulators that can activate or inhibit autophagy. Herein we review the current landscape in the development of screening technology as well as the molecules and pharmacologic agents targeting the regulatory mechanisms of autophagy. We also evaluate the potential therapeutic application of these compounds in different human pathologies.

Introduction Adverse drug reactions (ADRs) are frequent and can occur during hospitalisation leading to either hospitalisation or prolongation of stay [1, 2]. Serious ADRs are fatal in 5% of cases, [...], Objective: To assess the characteristics of life-threatening adverse drug reactions in patients admitted to medical intensive care unit and to define those that could facilitate early identification. Design: A prospective 6-month observational study. Patients: Of the 436 admissions to the teaching hospital medical intensive care unit, all patients aged over 15 years and who had received documented drug treatment were included (n = 405). Measurements: Characteristics of patients [age, gender, underlying diseases, organ failure(s), drugs taken, Severity Acute Physiologic Score II, length of stay, outcome at discharge] were prospectively collected using a standardised questionnaire. A panel of experts assessed putative serious adverse drug reaction(s) for each drug taken and each organ failure at admission by using a standardised causality assessment method. Characteristics of patients with and without serious adverse drug reactions at admission were compared using univariate and then stepwise descending multivariate logistic regression. Results: Of the 405 patients included, 111 (27.4%) presented an adverse drug reaction leading to organ failure. In 48% of cases adverse drug reactions were preventable, 23% were undiagnosed and 19% contributed to death. Age over 75 years [odds ratio (OR) 2.25; 95% confidence interval (CI) 1.15-4.38; p = 0.02], having more than three drugs (OR 6.90; 95% CI 1.44-33.00; p = 0.02) and a diagnosis of haematological malignancy (OR 6.19; 95% CI 2.07-18.53; p = 0.001) were independently associated with serious adverse drug reactions. Conclusions: Preventable life-threatening adverse drug reactions were frequently involved in organ failure at admission to medical intensive care; many of them had not been identified. Keywords Serious adverse drug reaction * Organ failure * Intensive care unit

Angelman syndrome is characterized by intellectual disability, epilepsy, impaired coordination and a characteristic joyful demeanour. Most commonly, it is caused by a deletion of five to six mega-bases of DNA [...]

Alcohol and other drugs are frequently used in combination (Martin 2008; National Institute on Alcohol Abuse and Alcoholism 2008). Based on data from the National Epidemiologic Survey on Alcohol and [...]

Drug treatments constitute a substantial portion of all health-care interventions. Despite their notable benefits, however, drug treatments are beyond the reach of sizable population groups and in some parts of [...]

Computational predictions could make it easier to design biopharmaceuticals that don't stick together. Aggregation can destroy the effectiveness of antibody-based drugs or, worse, spur an unwanted immune response. But current [...]