Extrarenal Effects of Aldosterone on Potassium Homeostasis

The role of aldosterone in regulating K+ excretion in the distal nephron is well established in kidney physiology. In addition to effects on the kidney, aldosterone modulates K+ and Na+ transport in salivary fluid, sweat, airway epithelia, and colonic fluid. More controversial and less well defined is the role of aldosterone in determining the internal distribution of K+ across cell membranes in non-transporting epithelia. In vivo studies have been limited by the difficulty in accurately measuring overall K+ balance and factoring in both variability and secondary changes in acid-base balance, systemic hemodynamics, and other K+-regulatory factors such as hormones and adrenergic activity. Despite these limitations, the aggregate data support a contributory role of aldosterone along with insulin and catecholamines in the normal physiologic regulation of internal K+ distribution. The authors speculate differences in tissue sensitivity to aldosterone may also contribute to differential tissue response of cardiac and skeletal muscle to conditions of total body K+ depletion.

Mechanisms and Models of Kidney Tubular Necrosis and Nephron Loss

Understanding nephron loss is a primary strategy for preventing chronic kidney disease (CKD) progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, during acute kidney injury (AKI), the transition of AKI to CKD, sepsis-associated AKI, and kidney transplantation, ferroptosis and necroptosis, two pathways associated with the loss of plasma membrane integrity, kill renal cells. This necrotic type of cell death is associated with an inflammatory response, which is referred to as necroinflammation. Importantly, the necroinflammatory response to cells that die by necroptosis may be fundamentally different from the tissue response to ferroptosis. While mechanisms of ferroptosis and necroptosis have recently been investigated in detail, the cell death propagation during tubular necrosis, although described morphologically, remains incompletely understood. Here, we argue that a molecular switch downstream of tubular necrosis determines nephron regeneration vs. nephron loss, respectively. Unravelling the details of this "switch" must include the inflammatory response to tubular necrosis and regenerative signals potentially controlled by inflammatory cells, including the stimulation of myofibroblasts as the origin of fibrosis. Understanding in detail the molecular switch and the inflammatory responses to tubular necrosis can inform discussion of therapeutic options.

Steroid-Responsive Post-Traumatic Persistent Neutrophilic Meningitis

Post-traumatic meningitis is a potentially fatal condition that presents as a diagnostic and therapeutic challenge. The vast majority of post-traumatic meningitides are caused by infectious pathogens, most commonly multi-drug-resistant (MDR) bacterial pathogens. However, aseptic meningitis occurs less frequently due to tissue response to injury or stimulation by noninfectious agents, such as blood breakdown products or chemicals. Here, we present a case of post-traumatic persistent neutrophilic meningitis who was found to be steroid responsive. Diagnostic evaluation in our patient did not reveal any infectious pathogen, and the patient did not respond to broad-spectrum antimicrobial treatment. We suggest that physicians who treat patients with post-traumatic meningitis should consider steroid-responsive post-traumatic persistent neutrophilic meningitis (SPNM) in the list of differential diagnosis particularly when no infectious etiology is found and the patient does not respond to empirical antimicrobial treatment. Brain injury-induced immune dysregulation causing exaggerated inflammatory reaction might play a role in the pathogenesis of SPNM; however, further neuropathological studies are absolutely necessary to evaluate and characterize trauma-induced immune dysregulation.

Improved Ablation Efficiency in PVI Guided by Contact Force and Local Impedance: Chronic Canine Model

Background: The purpose of this study was to assess the effect local impedance (LI) has on an ablation workflow when combined with a contact force (CF) ablation catheter.Methods: Left pulmonary vein isolation was performed in an in vivo canine model (N = 8) using a nominal (30 W) or an elevated (50 W) power strategy with a CF catheter. The catheter was enabled to measure LI prior to and during ablation. LI was visible for only one of the vein isolations.Results: Chronic block was achieved in all animals when assessed 30 ± 5 days post-ablation procedure with a median LI drop during RF ranging from 23.0 to 34.0 Ω. In both power cohorts, the median radiofrequency (RF) duration decreased if LI was visible to the operator (30 W only CF: 17.0 s; 30 W CF + LI: 14.0 s, p = 0.009; 50 W only CF: 6.0 s; 50 W CF + LI: 4.0 s, p = 0.019). An inverse relationship between the LI prior to RF delivery and the RF duration required to achieve an effective lesion was observed. There was no correlation between the magnitude of the applied force and the drop in LI, once at least 5 g was achieved.Conclusions: An elevated power strategy with the context of CF and LI led to the most efficient titration of successful RF energy delivery. The combination of feedback allows for customization of the ablation strategy based on local tissue variation rather than a uniform approach that could potentially lead to overtreatment. Higher LI drops were more readily achievable when an elevated power strategy was utilized, especially in conditions where the catheter was coupled against tissue with low resistivity. Clinical study is warranted to determine if there is an additive safety benefit to visualizing the dynamics of the tissue response to RF energy with LI when an elevated power strategy is used.

Risky interpretations across the length scales: continuum vs. discrete models for soft tissue mechanobiology

Modelling and simulation in mechanobiology play an increasingly important role to unravel the complex mechanisms that allow resident cells to sense and respond to mechanical cues. Many of the in vivo mechanical loads occur on the tissue length scale, thus raising the essential question how the resulting macroscopic strains and stresses are transferred across the scales down to the cellular and subcellular levels. Since cells anchor to the collagen fibres within the extracellular matrix, the reliable representation of fibre deformation is a prerequisite for models that aim at linking tissue biomechanics and cell mechanobiology. In this paper, we consider the two-scale mechanical response of an affine structural model as an example of a continuum mechanical approach and compare it with the results of a discrete fibre network model. In particular, we shed light on the crucially different mechanical properties of the ‘fibres’ in these two approaches. While assessing the capability of the affine structural approach to capture the fibre kinematics in real tissues is beyond the scope of our study, our results clearly show that neither the macroscopic tissue response nor the microscopic fibre orientation statistics can clarify the question of affinity.

Pyogenic Granuloma of Lower Lip: An Unusual Presentation

Pyogenic granuloma is a benign inflammatory hyperplasia of connective tissue. It depicts an overzealous tissue response to a known stimulus or injury and is commonly found in the gingiva, especially in the anterior maxilla, and rarely on lips, oral mucosa, and tongue. It is commonly seen during the second, third, and fourth decade in females, with predilection in the third decade. This case report depicts the unusual presentation of pyogenic granuloma of the lower lip in an 11-year-old male child following a positive history of trauma and lip biting, which was successfully managed by excision under local anesthesia.

Response of sweet cherry buds and twigs to temperature changes – evaluated by the determination of the degradation and synthesis of sucrose

This study was undertaken to determine the degradation and synthesis of sucrose (Suc) in sweet cherry buds and the twig tissue response to a sequence of environmental temperature changes (cold (orchard) – warm (controlled temperature of ∼22 °C) – cold (orchard)). The results of two years’ (2016, 2017) findings were compared with the buds of trees and the buds of twigs in November/December in northeast Germany. The Suc content in the buds of trees and the buds of twigs under natural conditions was stable. Temperatures of ∼22 °C resulted in a significant (Suc) degradation (62%, from 39 to 15 mg/g DW) in the buds of twigs after 21 days (day of the year (DOY) 340). The significant re-synthesis (66%, to 25 mg/g DW after 21 days, DOY 361) in the orchard is noteworthy, and highlights the Suc value as a cryoprotective saccharide. The marked changes in the Suc, glucose, and fructose contents of the twigs exposed to a cold-warm-cold sequence (< DOY 319, DOY 319–340, DOY 340–361), lead to the conclusion that this adaptation is the result of tissue- and cold-specific sucrose invertases/synthases. The effect of low-temperature-active enzymes explains the role of Suc in the buds of trees during the winter rest. When using twigs for plant physiological examinations during the winter rest, results on a metabolite level should be considered when drawing conclusions concerning the overall tree physiology.

Evaluation of Cytotoxicity and Biocompatibility of Ti2AlC in Rabbits

Background: The Titanium and its alloys are suitable for dental implant and medical applications. Biocompatibility of the materials is a major factor in determining the success of the implant and has a great impact on their rate of osseointegration. The aim of this study was to evaluate the biocompatibility and cytotoxicity of Ti2AlC in comparison to CPTi & Ti6Al7Nb in rabbits. Materials and Methods: 10 male New Zealand White rabbits, weighing (2-2.5 kg), aged (10-12 months) were used in this study. Cylindrical implants were prepared from the study materials (CPTi, Ti6Al7Nb and Ti2AlC) with (8mm) height and (3mm) diameter for the evaluation of tissue response and disc specimens were prepared with (6 mm) diameter and (2 mm) thickness for evaluation of cytotoxicity MTT test. A histological study was performed at 2 & 6 weeks post- surgical implant insertion. Results: Histological findings show that Ti2AlC has enhanced proliferation of osteo-progenitor cell and reported mature bone formation at 6 weeks. Moreover, Ti2AlC has recorded a higher percentage for viable cells by MTT test in comparison to CPTi and Ti6Al7Nb. Conclusion: The new Ti2AlC dental implant is considered biocompatible and has showed a better bone formation than the CPTi and Ti6Al7Nb materials at 2 & 6 weeks.