AMPK in Pathogens

During host–pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host–pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.CIHR -Canadian Institutes of Health Researc

The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted

Diagnosis and treatment of prostatic abscess

OBJECTIVES: Present and discuss the pathogenesis, diagnostic methods and treatment of the prostatic abscess. MATERIALS AND METHODS: We have retrospectively studied the medical records of 9 patients diagnosed and treated for prostatic abscess, between March 1998 and December 2000, assessing age, context, associated diseases, and diagnostic and therapeutic methods. We have compared the data found with those described in literature, based on Medline data. RESULTS: Mean age was 52.6 years. Three patients had previous diabetes mellitus diagnosis, and one was infected by HIV virus. Transrectal ultrasound of the prostate confirmed the diagnosis of prostatic abscess in all 7 cases in which it was performed. All cases received antibiotic treatment, and 77.8% needed concomitant surgical treatment. Two cases of microabscess were treated only with antibiotics. Four patients were submitted to perineal catheter drainage, 2 were submitted to transurethral resection of the prostate (TURP), and one patient required both procedures. Mean hospitalization time was 11.2 days, and most frequent bacterial agent was S. aureus. All patients were discharged from the hospital, and there was no death in this series. CONCLUSIONS: Prostatic abscess should be treated with broad-spectrum antibiotics and surgical drainage (perineal puncture or TURP). Microabscess may heal without surgery