Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood–Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats

Brain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term neurological benefits by preserving the function of the blood–brain barrier and glymphatic system after SAH. Pretreatment of inhibitors of PACAP receptors showed that the PACAP-involved anti-edema effect and neuroprotection after SAH was facilitated by the selective PACAP receptor (PAC1). Further administration of adenylyl cyclase (AC) inhibitor and sulfonylurea receptor 1 (SUR1) CRISPR activator suggested that the AC–cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) axis participated in PACAP signaling after SAH, which inhibited the expression of edema-related proteins, SUR1 and aquaporin-4 (AQP4), through SUR1 phosphorylation. Thus, PACAP may serve as a potential clinical treatment to alleviate brain edema in patients with SAH.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00925-3) contains supplementary material, which is available to authorized users.Key Words: Subarachnoid hemorrhage, brain edema, pituitary adenylate cyclase-activating polypeptide, blood–brain barrier, glymphatic system     

Tryptophan-kynurenine profile in pediatric autoimmune hepatitis

Immunologic Research - The impairment of regulatory T cells (Tregs) is a characteristic feature of autoimmune hepatitis (AIH), and the degradation of tryptophan (Trp) to kynurenine (Kyn), by gamma...     

Shaping Physiological Indices,Swimming Technique,and Their Influence on 200m Breaststroke Race in Young Swimmers

The aim of this study was to investigate somatic properties and physiological capacity, and analyze kinematic parameters in the 200 m breaststroke swimming race. Twenty-seven male swimmers participated in the study. They were 15.7±1.98 years old. Their average height was 1.80 ± 0.02 m and lean body mass (LBM) was 62.45 ± 8.29 kg. Physiological exercise capacity was measured in two separate 90 sec. all-out tests, one for the arms and second for legs. During the tests total work of arm cranking (TWAR) and cycling (TWLG) as well as peak of VO₂ for arm (VO_2peakAR) and leg (VO_2peakLG) were measured. The underwater swimmers body movements were recorded during the all-out swimming 200m breaststroke speed test using an underwater camera installed on a portable trolley. The swimming kinematic parameters and propulsive or non-propulsive movement phases of the arms and legs as well as average speed (V200), surface speed (V200surface) and swimming speed in turn zones (V200turns) were extracted. V200surface was significantly related to the percentage of leg propulsion and was shown to have large effect on VO_2peakLG in the Cohen analysis. V200turns depended significantly on the indicators of physiological performance and body structure: TWAR, VO_2peak LG and LBM, LBM, which in turn strongly determined the measured results of TWAR, TWLG, VO_2peakAR and VO_2peakLG. The V200turns and V200surface were strongly associated with V200, 0.92, p < 0.001 and 0.91, p < 0.001 respectively. In each lap of the 200m swimming there was an increased percentage of propulsion of limb movement observed simultaneously with a reduction in the gliding phase in the breaststroke cycles.

Key points

• This study investigated the influence of the selected indicators of somatic properties and physiological capacity as well kinematic and coordination parameters on breaststroke swimming.
• In this observations the body’s functional capacity have an important impact on achieving good breaststroke swimming results, the V₂₀₀ was moderately associated on VO₂peakLG, moreover, separate V₂₀₀turns depended with VO₂peakLG and on LBM and TWAR.
• The speed of surface breaststroke swimming - V₂₀₀surface similarly as V₂₀₀turns had a very strong influence on the end result of V_{200 ,} 0.91, p<0.001 and 0.92, p<0.001 respectively.
• The ability to swim fast on the surface (V₂₀₀surface) was positively and significantly associated with the percentage time of propulsion generation -LP in the breaststroke cycle.

Key words: Breaststroke swimming, physiological indices, lean body mass, kinematic indices     

Engineering Analysis of Tricuspid Annular Dynamics in the Beating Ovine Heart

Functional tricuspid regurgitation is a significant source of morbidity and mortality in the US. Furthermore, treatment of functional tricuspid regurgitation is suboptimal with significant recurrence rates, which may, at least in part, be due to our limited knowledge of the relationship between valvular shape and function. Here we study the dynamics of the healthy in vivo ovine tricuspid annulus to improve our understanding of normal annular deformations throughout the cardiac cycle. To this end, we determine both clinical as well as engineering metrics of in vivo annular dynamics based on sonomicrometry crystals surgically attached to the annulus. We confirm that the tricuspid annulus undergoes large dynamic changes in area, perimeter, height, and eccentricity throughout the cardiac cycle. This deformation may be described as asymmetric in-plane motion of the annulus with minor out-of-plane motion. In addition, we employ strain and curvature to provide mechanistic insight into the origin of this deformation. Specifically, we find that strain and curvature vary considerable across the annulus with highly localized minima and maxima resulting in aforementioned configurational changes throughout the cardiac cycle. It is our hope that these data provide valuable information for clinicians and engineers alike and ultimately help us improve treatment of functional tricuspid regurgitation.     

The application of L-PRP in AIDS patients with crural chronic ulcers: A pilot study

Purpose

Nonhealing wounds or skin ulcerations are the result of insufficient repair and destruction of a local healing potential. Opportunistic infections which cause a lot of ulcer complications influence the worsening general condition of patients with AIDS, ultimately leading to death. The chronicity of the condition and poor results of conventional therapy have prompted the search for new methods of treatment.

A similar pro/anti-inflammatory cytokine balance is present in the airways of competitive athletes and non-exercising asthmatics

Purpose

Intensive exercise modifies airway inflammation and infection susceptibility. We aimed to determine the effect of exercise on pro- and anti-inflammatory cytokine (TNF-α, IL-1ra, IL-10) and innate immunity protein (HSPA1, sCD14) levels in exhaled breath condensate (EBC) and nasal secretions of competitive athletes, non-exercising asthmatics and healthy controls (HC).

The release of metal ions from orthodontic appliances: Animal tests

Objective:To investigate the release of metal ions from an orthodontic appliance in tests on animals (pigs).Materials and Methods:An animal test was conducted on 24 pigs divided equally into an experimental and a control group. In total, 12 sets of experimental orthodontic plates were surgically inserted into pig snouts in the experimental group for 6 months. Noninvasive matrices (hair [0, 3, and 6 months]) and invasive matrices (kidneys, liver, lungs, aorta, and oral mucosa) were collected for multi-elemental analysis (inductively coupled plasma optical emission spectrometry) from the experimental and control groups.Results:The greatest differences in the content of toxic metals were found in the aorta (Ni level was 4.8 times higher in experimental than in the control group), in the cheek (Ni 3.5 times higher), and in the hair sampled after 3 months (Cr 3.4 times higher).Conclusions:The obtained data indicate that the products of corrosion have passed into selected tissues of pigs; however, the doses of toxic metal ions released from the appliance did not reach toxic levels.     

Effects of quinidine on pharmacokinetics and pharmacodynamics of digitoxin achieving steady-state conditions

Quinidine has been reported to increase digoxin plasma concentrations, which increases the risk of digoxin overdose. The effect of quinidine on digitoxin pharmacokinetics is still controversial because most studies were not performed with subjects achieving definite steady-state conditions. To determine whether quinidine affects digitoxin kinetics and cardiac efficacy, we measured glycoside plasma concentrations and renal excretion as well as ECG parameters and systolic time intervals before and during quinidine dosing in eight healthy subjects at steady state. Mean (+/- SD) digitoxin plasma concentrations and renal excretion increased from 13.6 +/- 2.2 ng/ml and 16.1 +/- 5.8 micrograms/24 hours before dosing to 19.7 +/- 3.1 ng/ml and 23.4 +/- 4.9 micrograms/24 hours, respectively, during quinidine dosing for 32 days. While renal digitoxin clearance was not noticeably changed by quinidine, total digitoxin clearance and extrarenal digitoxin clearance decreased by an average of 32% and 40.5%, respectively. The elimination t1/2 was prolonged from 150.3 +/- 20.6 to 202.6 +/- 37.5 hours. The increased digitoxin plasma level is pharmacodynamically active. We conclude that there is a clinically important interaction between digitoxin and quinidine, but it is to a lesser extent and is caused by different mechanism, in part, than the interaction between digoxin and quinidine.