Engineered Andrographolide Nanoparticles Mitigate Paracetamol Hepatotoxicity in Mice

Purpose

Paracetamol (acetaminophen, APAP) overdose is often fatal due to progressive and irreversible hepatic necrosis. The aim of this work was to design Andrographolide (AG) loaded nanoparticles to prevent similar hepatic necrosis.

Methods

Functionalized AG-loaded PLGA nanoparticles carrying different densities of heparin were prepared following a facile emulsion solvent evaporation technique. Nanoparticle morphology, loading and release kinetics were studied. Hepatic localization of the nanoparticles was investigated in both normal and APAP damaged conditions using FITC fluorescent probe. Different serum parameters and liver histopathology were further examined as indicators of hepatic condition before and after treatment.

Result

A collection of heparin functionalized AG-loaded PLGA nanoparticles were designed. Low amount of heparin on the particle surface could rapidly localize the nanoparticles up to the liver. The new functionalized AG nanoparticles affect efficient hepatoprotection in experimental mouse APAP overdose conditions. AG nanoparticle hepatoprotection was due to the rapid regeneration of antioxidant capacity and hepatic GSH store.

Conclusions

Engineered nanoparticles loaded with AG provided a fast protection in APAP induced acute liver failure.     

Stabilization and encapsulation of photosensitive resveratrol within yeast cell

The photosensitive resveratrol was successfully encapsulated in yeast cells for the first time, as characterized by FT-IR spectra, fluorescence and confocal micrographs of the yeast cells, resveratrol and microcapsules. The release characteristic of the obtained yeast-encapsulated resveratrol in simulated gastric fluid was evaluated, and its storage stability as a powder was investigated at 25 degrees C/75% relative humidity (RH), 25 degrees C/90% RH and 60 degrees C under the laboratory fluorescent lighting conditions (ca. 300 lx) or in the dark. Also, the scavenging capacity of yeast-encapsulated resveratrol on DPPH radical was compared with that of non-encapsulated resveratrol. It could be demonstrated clearly that no chemical changes occurred during the encapsulation. Besides, the DPPH radical-scavenging activity increased after the encapsulation. In addition, the yeast-encapsulated resveratrol exhibited good stability, and its bioavailability was enhanced as a result of increased solubility of resveratrol and sustained releasing.     

A retrospective analysis of risk factors for clavicle fractures in newborns with shoulder dystocia and brachial plexus injury: A single-center experience

ObjectiveWe aimed to analyze the risk factors for clavicle fractures in newborns with shoulder dystocia and brachial plexus injury and to determine whether their incidence is associated with local characteristics.MethodsThis study was conducted as a retrospective trial between January 2017 and December 2018. Patients with clavicular fracture who were hospitalized in the neonatal intensive care unit of a community hospital were retrospectively analyzed. The clavicular fracture cohort was first divided into two groups and then two subgroups: patients with/without shoulder dystocia and patients with/without a brachial plexus injury. Peripartum and neonatal risk factors of these patients were reviewed using the patient information system. Any additional neurological or musculoskeletal trauma was noted. A multivariate logistic regression analysis was performed to determine independent predictors of shoulder dystocia and brachial plexus injury.ResultsA total of 46 patients with shoulder dystocia in 25 (54%) and brachial plexus injury in 12 (26%) were included in the study. The birth weight of patients with shoulder dystocia was 4,164.2±412.7 g, and that of patients without was 3,535.8±865.2 g (p=0.003). In 11 of 14 patients (44%) in whom labor was induced and whose infant had a fractured clavicle, the infant also had shoulder dystocia (p=0.029). Brachial plexus injury was found in 8 (66.7%) of 14 infants who were born by induced labor and who had a clavicular fracture (p=0.002). The regression analysis revealed that age and induction of labor were independent risk factors for brachial plexus injury (odds ratio=1.599 and 81.862, respectively). Gestational weight gain (p=0.003) and neonatal birth weight (p=0.047) were also found as independent risk factors for shoulder dystocia.ConclusionEvidence from this study has shown that not only birth age or birth weight but also excessive weight gain by mother and induction of labor may increase the risk of clavicula fracture with brachial plexus palsy. Advanced maternal age, multiparity, and deliveries after 39 weeks seem to be risk factors for a clavicular fracture with a brachial plexus injury.Level of EvidenceLevel IV, Therapeutic study     

A catch‐up validation study of an in vitro skin irritation test method using reconstructed human epidermis LabCyte EPI‐MODEL24

Three validation studies were conducted by the Japanese Society for Alternatives to Animal Experiments in order to assess the performance of a skin irritation assay using reconstructed human epidermis (RhE) LabCyte EPI‐MODEL24 (LabCyte EPI‐MODEL24 SIT) developed by the Japan Tissue Engineering Co., Ltd. (J‐TEC), and the results of these studies were submitted to the Organisation for Economic Co‐operation and Development (OECD) for the creation of a Test Guideline (TG). In the summary review report from the OECD, the peer review panel indicated the need to resolve an issue regarding the misclassification of 1‐bromohexane. To this end, a rinsing operation intended to remove exposed chemicals was reviewed and the standard operating procedure (SOP) revised by J‐TEC. Thereafter, in order to confirm general versatility of the revised SOP, a new validation management team was organized by the Japanese Center for the Validation of Alternative Methods (JaCVAM) to undertake a catch‐up validation study that would compare the revised assay with similar in vitro skin irritation assays, per OECD TG No. 439 (2010). The catch‐up validation and supplementary studies for LabCyte EPI‐MODEL24 SIT using the revised SOPs were conducted at three laboratories. These results showed that the revised SOP of LabCyte EPI‐MODEL24 SIT conformed more accurately to the classifications for skin irritation under the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS), thereby highlighting the importance of an optimized rinsing operation for the removal of exposed chemicals in obtaining consistent results from in vitro skin irritation assays. Copyright © 2013 John Wiley & Sons, Ltd.     

Seasonal variation of human sperm cells among 4,422 semen samples: A retrospective study in Turkey

We aimed to assess the possible presence of a seasonal pattern in three parameters of semen analysis: sperm concentration, morphology, and motility as a function of the time of ejaculation and sperm production (spermatogenesis) in normal and oligozoospermic men. This retrospective study included a consecutive series of 4,422 semen samples that were collected from patients as a part of the basic evaluation of the infertile couples attending the Reproductive Endocrine Outpatient Clinic of a tertiary women’s hospital in Ankara, Turkey, between January 1, 2012 and December 31, 2013. The samples were classified according to sperm concentration: ≥15 x10⁶/mL as normozoospermic samples and 4 -14.99 x10⁶/mL as oligozoospermic samples and seasonal analysis of the semen samples were carried out separately. When the data was analyzed according to the season of semen production, there was no seasonal effect on the sperm concentration. A gradual and consistent decrease in the rate of sperm with fast forward motility was observed from spring to fall with a recovery noticed during the winter. The percentage of sperms with normal morphology was found to be statistically significantly higher in the spring samples compared with the summer samples (p=0.001). Both normozoospermic and oligozoospermic semen samples appeared to have better sperm parameters in spring and winter. The circannual variation of semen parameters may be important in diagnosis and treatment desicions.

Abbreviations: WHO: World Health Organization; mRNA:messenger ribonucleic acid     

Features of wound healing shown by fibroblasts obtained from the superficial and deep dermis

Dermal fibroblasts (DF) obtained from the superficial dermal layer and those from the deep dermal layer have different cellular functions. These differences are often associated with excessive scarring; they also influence early wound healing. We therefore investigated the differences between superficial and deep dermal fibroblasts with special emphasis on their contractile properties, and ability to produce connective tissue. We investigated their proliferation kinetics, ability to contract collagen lattices, and chronological mRNA expression of eight genes associated with wound healing. To estimate the changes in the differences between them during the early phase of wound healing, we investigated mRNA expression in bFGF supplemented medium because bFGF is a representative cytokine that is familiar to clinicians. Superficial DF proliferate faster than deep DF in culture, whereas deep DF are better at contracting collagen lattices than superficial ones. In realtime analysis of polymerase chain reaction, the expression of type I and III collagen, fibronectin, TGF β1 and β3, and connective tissue growth factor were higher in deep DF than in superficial DF, while the expression of TGF β2 was higher in superficial DF. After bFGF supplementation, the relative dominance of mRNA expression between superficial and deep DF remained constant except for the expression of collagenase. According to our analysis, deep DF are superior to superficial DF at promoting wound healing (particularly contraction and production of connective tissue). The intradermal distribution of DF is appropriate for efficient wound healing.     

Increased comorbidities in heart failure patients ≥ 85 years but declined from > 90 years: Data from the Swedish Heart Failure Registry

Objectives

Epidemiological studies of elderly heart failure (HF) patients (≥ 85 years) are limited with inconsistent findings. Our objective is to confirm and extend epidemiological study in elderly (≥ 85 years) patients using the Swedish Heart Failure Registry database.

Methods

This retrospective study included 8,347 HF patients aged ≤ 65 years and 15,889 HF patients aged ≥ 85 years. Elderly population was further divided into two subgroups: 11,412 patients were 85–90 years and 4,477 patients were > 90 years.

Results

The ≥ 85 year group was characterized by more women, higher systolic blood pressure (SBP), lower body-mass index (BMI), more than twice as many HF with normal left ventricular ejection fraction (HFNEF), higher incidence of cardiovascular and non-cardiovascular comorbidities and less use of proven therapeutics compared with the ≤ 65 year group. Compared with the 85–90 year subgroup, the > 90 year subgroup had a decline in cardiovascular and non-cardiovascular comorbidities except renal insufficiency and anaemia which continued to increase with ageing (p < 0.01). Tendency was the same regardless of gender but slightly different between systolic HF (SHF) and HFNEF. In the group with HFNEF, there were more women, higher SBP, lower N-terminal pro-B-type natriuretic peptide levels, less ischaemic heart disease, more hypertension and left bundle branch block regardless of age. Atrial fibrillation was more frequent in patients with HFNEF than with SHF in the elderly group (p < 0.01). Patients with HFNEF in the > 90 year subgroup had increasing incidence of ischaemic heart disease compared to 85–90 year group (p < 0.01).

Conclusions

HF patients ≥ 85 years had increased cardiovascular and non-cardiovascular comorbidities but with a decline from > 90 years.