A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor

GeroScience - A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations,...     

Double-balloon enteroscopy for the diagnosis and treatment of obscure bleeding, inflammatory bowel diseases and polyposis syndromes: we see more but do we know more?

BACKGROUND/AIMS: Our aim was to report our experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope (DBE) in the diagnosis of small bowel diseases. METHODOLOGY: Between August 2005 and October 2006, 52 DBE procedures were conducted on 47 consecutive patients (M/F: 22/25, age: 51.6 SD 19.5 years) presenting at our tertiary referral hospital (35 and 7 patients from oral and anal route, respectively; 5 patients from both). All procedures were performed using i.v. anesthesia, at our outpatient clinic. RESULTS: Indication suspected small-bowel bleeding in 28 patients, suspected/known inflammatory bowel syndrome (IBD) in 12 and polyposis/suspected neoplasia in 7. In obscure bleeding small-bowel abnormality was found in 18 patients (64.3%) including angiodysplasias/erosions and one polypoid lesion. In suspected IBD, IBD was diagnosed in 2 out of 8 cases. In patients with polyposis syndromes, polyps were in two Peutz-Jeghers patients, while a further patient with suspected stenosis was diagnosed with primary adenocarcinoma. The average insertion length was app. 213cm. No severe complications were observed. CONCLUSIONS: Based on our experience DBE is a safe and useful method for evaluating and treating small bowel disease in selected patients with obscure bleeding, IBD or polyposis syndromes, however the clinical importance of minute lesions still needs to be determined.     

Chaperone function and chaperone overload in the aged. A preliminary analysis

Chaperones have an important role in the repair of proteotoxic damage, which is greatly increased in aged subjects. Chaperone levels and expression were subject of numerous studies in aged organisms. However, there were only very few attempts to measure chaperone activity in aged animals. Here, we report our initial studies showing a decreased chaperone capacity of liver cytosol from aged rats compared to those of young counterparts. The amount of Hsc70/Hsp70 was not significantly different in livers of young and aged rats. On the contrary, old animals showed a significant decrease in their hepatic Hsp90 content, which may explain their decreased chaperone activity. The observed decrease in chaperone capacity may also reflect a direct proteotoxic damage of chaperones, or an increase in chaperone occupancy, i.e. a 'chaperone overload' due to the increased amount of damaged hepatic proteins in aged rats. Experiments are in progress to elucidate the mechanism of the observed age-induced changes in chaperone function.     

Evaluation of the Histomorphometric and Micromorphometric Performance of a Serum Albumin-Coated Bone Allograft Combined with A-PRF for Early and Conventional Healing Protocols after Maxillary Sinus Augmentation: A Randomized Clinical Trial

The aim of this study was to compare the microarchitecture of augmented bone following maxillary sinus augmentation (MSA) after healing periods of 3 (test) and 6 (control) months using the combination of advanced platelet-rich fibrin (A-PRF) and a serum albumin-coated bone allograft (SACBA). Twenty-six patients with 30 surgical sites who required two-stage MSA were enrolled and grafted with the combination of A-PRF and SACBAs. The surgical sites were randomly allocated to the test or control group. During implant site preparation, 17 bone core biopsy samples were collected from each study group for histological, histomorphometric and micromorphometric analysis. Resonance frequency analysis was performed at the time of implant placement and 6, 8, 10, and 12 weeks postoperatively. The percentage of newly formed bone was 44.89 ± 9.49% in the test group and 39.75 ± 8.15% in the control group (p = 0.100). The results of the µCT analysis showed no significant differences in morphometric parameters between the study groups. The implant stability quotient was not significantly different between the two groups at 10 and 12 weeks postoperatively. Based on these findings, the total treatment time may be reduced by 3 months with the use of A-PRF and SACBAs for two-stage MSA.     

Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post‐hypoxic cardiomyocytes

Background and Purpose

Ischaemic heart disease can lead to serious, life‐threatening complications. Traditional therapies for ischaemia aim to increase oxygen delivery and reduce the myocardial ATP consumption by increasing the coronary perfusion and by suppressing cardiac contractility, heart rate or blood pressure. An adjunctive treatment option for ischaemia is to improve or optimize myocardial metabolism.

Experimental Approach

Metabolic suppression in the ischaemic heart is characterized by reduced levels of high‐energy molecules: ATP and NAD⁺. Because NAD⁺ is required for most metabolic processes that generate ATP, we hypothesized that restoration of NAD⁺ would be a prerequisite for ATP regeneration and examined the role of the major NAD⁺ anabolic and catabolic pathways in the bioenergetic restoration process following oxygen–glucose deprivation injury in a cardiomyocyte cell line (H9c2 cells).

Key Results

Salvage of NAD⁺ via nicotinamide phosphoribosyl transferase was essential for bioenergetic recovery in cardiomyocytes. Blockade of nicotinamide phosphoribosyl transferase prevented the restoration of the cellular ATP pool following oxygen–glucose deprivation injury by inhibiting both the aerobic and anaerobic metabolism in the cardiomyocytes. NAD⁺ consumption by PARP‐1 also undermined the recovery processes, and PARP inhibition significantly improved the metabolism and increased cellular ATP levels in cardiomyocytes.

Conclusions and Implications

We conclude that the NAD⁺ salvage pathway is essential for bioenergetic recovery in post‐hypoxic cardiomyocytes and PARP inhibition may represent a potential future therapeutic intervention in ischaemic heart disease.

Abbreviations

CVD

cardiovascular disease

FK866

(E)‐N‐[4‐(1‐benzoylpiperidin‐4‐yl)butyl]‐3‐(pyridin‐3‐yl)acrylamide

JC‐1

5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐imidacarbocyanine iodide

MitoSOX Red

MitoSOX™ Red mitochondrial superoxide indicator

MTT

3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide

NamPRT

nicotinamide phosphoribosyltransferase

NMNAT

nicotinamide mononucleotide adenylyl transferase

OGD

oxygen–glucose deprivation

PJ34

N‐(6‐oxo‐5,6‐dihydrophenanthridin‐2‐yl)‐(N,N‐dimethylamino) acetamide hydrochloride

RNF146

ring finger protein 146

     

Development and Validation of Prediction Scores for Early Mortality at Transition to Dialysis

Objective

To develop and validate a risk prediction model that would help individualize treatment and improve the shared decision-making process between clinicians and patients.

Efficient Non-viral Gene Delivery into Human Hematopoietic Stem Cells by Minicircle Sleeping Beauty Transposon Vectors

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Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part I. Biochemical and physiological mechanisms

Until recently, hydrogen sulfide (H₂S) was exclusively viewed a toxic gas and an environmental hazard, with its toxicity primarily attributed to the inhibition of mitochondrial Complex IV, resulting in a shutdown of mitochondrial electron transport and cellular ATP generation. Work over the last decade established multiple biological regulatory roles of H₂S, as an endogenous gaseous transmitter. H₂S is produced by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). In striking contrast to its inhibitory effect on Complex IV, recent studies showed that at lower concentrations, H₂S serves as a stimulator of electron transport in mammalian cells, by acting as a mitochondrial electron donor. Endogenous H₂S, produced by mitochondrially localized 3-MST, supports basal, physiological cellular bioenergetic functions; the activity of this metabolic support declines with physiological aging. In specialized conditions (calcium overload in vascular smooth muscle, colon cancer cells), CSE and CBS can also associate with the mitochondria; H₂S produced by these enzymes, serves as an endogenous stimulator of cellular bioenergetics. The current article overviews the biochemical mechanisms underlying the stimulatory and inhibitory effects of H₂S on mitochondrial function and cellular bioenergetics and discusses the implication of these processes for normal cellular physiology. The relevance of H₂S biology is also discussed in the context of colonic epithelial cell physiology: colonocytes are exposed to high levels of sulfide produced by enteric bacteria, and serve as a metabolic barrier to limit their entry into the mammalian host, while, at the same time, utilizing it as a metabolic ‘fuel’.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8