Receptor-Independent Therapies for Forensic Detainees with Schizophrenia-Dementia Comorbidity.

Forensic institutions throughout the world house patients with severe psychiatric illness and history of criminal violations. Improved medical care, hygiene, psychiatric treatment, and nutrition led to an unmatched longevity in this population, which previously lived, on average, 15 to 20 years shorter than the public at large. On the other hand, longevity has contributed to increased prevalence of age-related diseases, including neurodegenerative disorders, which complicate clinical management, increasing healthcare expenditures. Forensic institutions, originally intended for the treatment of younger individuals, are ill-equipped for the growing number of older offenders. Moreover, as antipsychotic drugs became available in 1950s and 1960s, we are observing the first generation of forensic detainees who have aged on dopamine-blocking agents. Although the consequences of long-term treatment with these agents are unclear, schizophrenia-associated gray matter loss may contribute to the development of early dementia. Taken together, increased lifespan and the subsequent cognitive deficit observed in long-term forensic institutions raise questions and dilemmas unencountered by the previous generations of clinicians. These include: does the presence of neurocognitive dysfunction justify antipsychotic dose reduction or discontinuation despite a lifelong history of schizophrenia and violent behavior? Should neurolipidomic interventions become the standard of care in elderly individuals with lifelong schizophrenia and dementia? Can patients with schizophrenia and dementia meet the Dusky standard to stand trial? Should neurocognitive disorders in the elderly with lifelong schizophrenia be treated differently than age-related neurodegeneration? In this article, we hypothesize that gray matter loss is the core symptom of schizophrenia which leads to dementia. We hypothesize further that strategies to delay or stop gray matter depletion would not only improve the schizophrenia sustained recovery, but also avert the development of major neurocognitive disorders in people living with schizophrenia. Based on this hypothesis, we suggest utilization of both receptor-dependent and independent therapeutics for chronic psychosis.

Sphingolipids and Cholesterol.

Sphingolipids and cholesterol are two lipid partners on cellular membranes where they form specific microdomains, named lipid rafts, which mediate specific cell functions. Sphingomyelin (SM) is one of the major sphingolipids. SM and free cholesterol are also two key lipids on the monolayer of plasma lipoproteins, including chylomicron, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which participate in lipid transport in the circulation. Thus, sphingolipids and cholesterol play a fundamental role in cell membrane structure and blood lipid transport. In this chapter we will discuss the relationship between both lipids, on the cell membrane and in the circulation, as well as the impact of such relationship in the development of metabolic diseases.

An In Vitro Study of the Effect of Viburnum opulus Extracts on Key Processes in the Development of Staphylococcal Infections.

Staphylococcus aureus is still one of the leading causes of both hospital- and community-acquired infections. Due to the very high percentage of drug-resistant strains, the participation of drug-tolerant biofilms in pathological changes, and thus the limited number of effective antibiotics, there is an urgent need to search for alternative methods of prevention or treatment for S. aureus infections. In the present study, biochemically characterized (HPLC/UPLC-QTOF-MS) acetonic, ethanolic, and water extracts from fruits and bark of Viburnum opulus L. were tested in vitro as diet additives that potentially prevent staphylococcal infections. The impacts of V. opulus extracts on sortase A (SrtA) activity (Fluorimetric Assay), staphylococcal protein A (SpA) expression (FITC-labelled specific antibodies), the lipid composition of bacterial cell membranes (LC-MS/MS, GC/MS), and biofilm formation (LIVE/DEAD BacLight) were assessed. The cytotoxicity of V. opulus extracts to the human fibroblast line HFF-1 was also tested (MTT reduction). V. opulus extracts strongly inhibited SrtA activity and SpA expression, caused modifications of S. aureus cell membrane, limited biofilm formation by staphylococci, and were non-cytotoxic. Therefore, they have pro-health potential. Nevertheless, their usefulness as diet supplements that are beneficial for the prevention of staphylococcal infections should be confirmed in animal models in the future.

The Cell Wall, Cell Membrane and Virulence Factors of Staphylococcus aureus and Their Role in Antibiotic Resistance.

Antibiotic resistant strains of bacteria are a serious threat to human health. With increasing antibiotic resistance in common human pathogens, fewer antibiotics remain effective against infectious diseases. Staphylococcus aureus is a pathogenic bacterium of particular concern to human health as it has developed resistance to many of the currently used antibiotics leaving very few remaining as effective treatment. Alternatives to conventional antibiotics are needed for treating resistant bacterial infections. A deeper understanding of the cellular characteristics of resistant bacteria beyond well characterized resistance mechanisms can allow for increased ability to properly treat them and to potentially identify targetable changes. This review looks at antibiotic resistance in S aureus in relation to its cellular components, the cell wall, cell membrane and virulence factors. Methicillin resistant S aureus bacteria are resistant to most antibiotics and some strains have even developed resistance to the last resort antibiotics vancomycin and daptomycin. Modifications in cell wall peptidoglycan and teichoic acids are noted in antibiotic resistant bacteria. Alterations in cell membrane lipids affect susceptibility to antibiotics through surface charge, permeability, fluidity, and stability of the bacterial membrane. Virulence factors such as adhesins, toxins and immunomodulators serve versatile pathogenic functions in S aureus. New antimicrobial strategies can target cell membrane lipids and virulence factors including anti-virulence treatment as an adjuvant to traditional antibiotic therapy.