A Spectrum of Topics for 2019: Advances in Neuroinflammation, Oxidative Stress, Obesity, Diabetes Mellitus, Cardiovascular Disease, Autism, Exosomes, and Central Nervous System Diseases.

Advances in various fields were discussed in the reviews and original research articles published in 2019 in Current Pharmaceutical Design. Here, I review some of the major highlights for selected areas. A better understanding of disease mechanisms was a prominent recurrent theme and new therapeutic targets based on those mechanisms are highlighted here.

Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis.

Background: Two coding variants in the apo L1 gene () are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results.

Patterns of Beverages Consumed and Risk of Incident Kidney Disease.

Background And Objectives: Selected beverages, such as sugar-sweetened beverages, have been reported to influence kidney disease risk, although previous studies have been inconsistent. Further research is necessary to comprehensively evaluate all types of beverages in association with CKD risk to better inform dietary guidelines.

Design, Setting, Participants, & Measurements: We conducted a prospective analysis in the Jackson Heart Study, a cohort of black men and women in Jackson, Mississippi.

Relation of uric acid level to rapid kidney function decline and development of kidney disease: The Jackson Heart Study.

Whether elevated uric acid (UA) is an independent risk factor for chronic kidney disease (CKD) is not well established. The authors evaluated the relationship of UA with rapid kidney function decline (RKFD) and incident CKD among 3702 African Americans (AAs) in the Jackson Heart Study with serum UA levels measured at baseline exam (2000-2004). RKFD was defined as ≥ 30% eGFR loss and incident CKD as development of eGFR < 60 mL/min/1.

Methods Employed to Assess Weight Loss in Older Adults by Means of Electronic Medical Records: A Systematic Review.

Electronic medical records (EMRs) can be used to identify and categorize weight loss in older adults, but research has not scrutinized methods for doing so. Through a modified PRISMA protocol, we systematically reviewed published methods for quantifying weight change from EMRs. Articles (all available through July 2016) were identified through PubMed and SCOPUS searches, screened, and evaluated.

Prolactin transport into mouse brain is independent of prolactin receptor.

The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood-brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF).

How to measure alterations in alveolar barrier function as a marker of lung injury.

The alveolar capillary membrane maintains the proper water and solute content of the epithelial lining fluid at the alveolar air-liquid interface, which is critical for adequate gas exchange in the lung. This is possible due to the alveolar fluid clearance (AFC) capacity of this membrane that assists in the removal of salt and water from the alveolar air spaces. The alveolar capillary membrane also provides a barrier that restricts the passage of proteins and water from the interstitial and vascular compartments into the alveolar air spaces.

The blood-brain barrier in neuroimmunology: Tales of separation and assimilation.

Neuroimmunology is concerned with the relations between the central nervous and immune systems and with the mechanisms that drive those relations. The blood-brain barrier (BBB) employs mechanisms that both separate and connect these two systems. In fact, the relative immune privilege of the central nervous system (CNS) is largely attributable to the BBB's ability to prevent the unregulated exchange of immune cells and their secretions between the CNS and blood.

Intrathecal delivery of protein therapeutics to the brain: a critical reassessment.

Disorders of the central nervous system (CNS), including stroke, neurodegenerative diseases, and brain tumors, are the world's leading causes of disability. Delivery of drugs to the CNS is complicated by the blood-brain barriers that protect the brain from the unregulated leakage and entry of substances, including proteins, from the blood. Yet proteins represent one of the most promising classes of therapeutics for the treatment of CNS diseases.

The Fas/FasL pathway impairs the alveolar fluid clearance in mouse lungs.

Alveolar epithelial damage is a critical event that leads to protein-rich edema in acute lung injury (ALI), but the mechanisms leading to epithelial damage are not completely understood. Cell death by necrosis and apoptosis occurs in alveolar epithelial cells in the lungs of patients with ALI. Fas activation induces apoptosis of alveolar epithelial cells, but its role in the formation of lung edema is unclear.

Insulin in the brain: there and back again.

Insulin performs unique functions within the CNS. Produced nearly exclusively by the pancreas, insulin crosses the blood-brain barrier (BBB) using a saturable transporter, affecting feeding and cognition through CNS mechanisms largely independent of glucose utilization. Whereas peripheral insulin acts primarily as a metabolic regulatory hormone, CNS insulin has an array of effects on brain that may more closely resemble the actions of the ancestral insulin molecule.

Effects of S-nitrosation and cross-linking of hemoglobin on hypoxic pulmonary vasoconstriction in isolated rat lungs.

Free hemoglobin (Hb) and red blood cells augment hypoxic pulmonary vasoconstriction (HPV) by scavenging nitric oxide (NO). S-nitrosation of Hb (SNO-Hb) may confer vasodilatory properties by allowing release of NO during deoxygenation and/or by interaction with small-molecular weight thiols. Likewise, cross-linking of free Hb may limit its vasoconstrictive effect by preventing abluminal movement of the molecule.

Structure and expression of the human septin gene HCDCREL-1.

Septins are a family of highly conserved filament-forming proteins that have been shown to mediate cytokinesis and cytoskeletal organization in fungi and Drosophila. The gene encoding the human septin family member HCDCREL-1 has been shown to be transcribed from a locus immediately adjacent to that of the platelet glycoprotein (GP) Ib b. The HCDCREL-1 gene possesses a non-consensus polyadenylation signal that apparently is not efficiently utilized, resulting in the expression of a readthrough transcript also containing the platelet GPIb beta coding region.

Hemodynamic response and change in organ blood volume during spinal anesthesia in elderly men with cardiac disease.

Aging and disease may make the elderly patient with cardiac disease particularly susceptible to hypotension during spinal anesthesia. We studied 15 men, 59-80 y old, with histories of prior myocardial infarction (n = 9), congestive heart failure (n = 2), and/or stable myocardial ischemia (n = 11) given spinal anesthesia with 50 mg lidocaine in dextrose. Technetium-99m-labeled red blood cell imaging estimated left ventricular ejection fraction (EF) and changes in blood volume in the abdominal organs and legs.