Cell-free DNA as a potential marker to predict carbon tetrachloride-induced acute liver injury in rats

Purpose

Finding an optimal biomarker for the noninvasive evaluation of acute liver injury (ALI) may be of great value in predicting clinical outcomes and investigating potential treatments. We investigated cell-free DNA (CFD) as a potential biomarker to predict carbon tetrachloride-induced ALI in rats.

Methods

Forty-five Sprague–Dawley rats were randomly assigned to three groups. ALI was induced by carbon tetrachloride via a nasogastric tube at 1, 2.5, or 5 ml/kg of a 50 % solution. Fifteen additional rats underwent a sham procedure. Blood samples were drawn at time t which was 0 (baseline), 3, 6, 12, 24, 48, 72, 96, and 120 h for the measurements of CFD, glutamate–pyruvate transaminase (GPT), glutamate–oxaloacetate transaminase (GOT), and total bilirubin. Prothrombin time and histology were examined at 24 and 120 h following injection of 5 ml/kg carbon tetrachloride in 18 additional rats and in 10 control rats.

Results

CFD levels in rats subjected to carbon tetrachloride-induced ALI were significantly increased in all blood samples starting at 12 h after the induction of ALI (p < 0.001), reaching peak levels at 24 h. Blood GOT, GPT, and total bilirubin were elevated in all blood samples starting at 3 h after the induction of ALI (p < 0.0001), reaching peak levels by 48 h. A positive correlation was demonstrated between CFD levels and GOT (R ² = 0.92), GPT (R ² = 0.92), and total bilirubin (R ² = 0.76). CFD levels correlated with liver damage seen on histological examination, as well as predicted liver damage, at 24 h after ALI.

Conclusions

CFD may be a useful biomarker for the prediction and measurement of ALI. There is no evidence to suggest that CFD is superior to other available noninvasive biomarkers.     

Intrathecal aspergillosis and fusiform arterial aneurysms in an immunocompromised child: a clinico-pathological case report

Case report We describe a 12-year-old boy with subarachnoid hemorrhage. Cerebral angiography revealed multiple fusiform intracranial arterial aneurysms. Surgical therapy other than ventricular drainage was not feasible due to the extent and pattern of pathological changes. Aspergillus antigen was found in the cerebrospinal fluid (CSF). However, cultures of urine, CSF, and samples from the upper airways were negative for Aspergillus and other fungi. The boy was immunocompromised due to prophylactic antibiotic therapy for recurrent pneumonia and continuous steroid therapy for his hemolytic anemia. There were Aspergillus antigens but no evidence of ongoing infection with the fungus was found. The patient suffered recurrent intraventricular hemorrhage and died on the 31st day after admission.Pathological examination Pathological examination showed multiple fusiform aneurysms, hypertrophy of the intima, and destruction of the internal elastic membrane of the cerebral arteries. No fungus infiltration was detected. We speculate that the patient had previously had an Aspergillus infection, causing segmental destruction of the internal elastic membrane. However, we cannot rule out noninfectious vasculitis as possible etiology.Conclusions In the immunocompromised child, fusiform segmental intracranial arterial aneurysms may be secondary to the destruction of the internal elastic membrane by fungus infection. The condition may present with aneurysm rupture and subarachnoid hemorrhage. In this patient group, surgical therapy is rarely an option and the prognosis is poor.     

Transforming growth factor-beta receptor type II mutation in a patient with bicuspid aortic valve disease and intraoperative aortic dissection

We report on a patient with familial bicuspid aortic valve disease operated on for proximal aortic aneurysm. The surgery was complicated by intraoperative aortic dissection. Multi-generational genetic analysis demonstrated a mutation in the transforming growth factor-beta receptor type II gene. This case confirms the clinical hypothesis that the proximal aortic disease has a genetic origin in some bicuspid aortic valve patients.     

Commentary: The need for research on PTSD in Children and adolescents – a commentary on Elliot et al. (2020)

The recent release of the 11th version of The International Classification of Diseases (ICD-11: WHO, 2018) marked a significant departure from the previous similarities between it and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; APA, 2013) in terms of their conceptualization of posttraumatic stress disorder (PTSD). The ICD-11 proposed a reduced symptom set for PTSD and a sibling disorder called Complex PTSD. There have been numerous studies that have provided support for the integrity of, and distinction between, PTSD and CPTSD diagnoses in adult samples. Elliot and colleagues (2020) have added to the research literature by providing a valuable examination of the differences between ICD and DSM PTSD/CPTSD in a sample of youth aged 8 to 17 years. This commentary reviews this study and reflects on the need for greater understanding of developmental changes in the presentation of PTSD and Complex PTSD.     

Protracted elimination of gold nanoparticles from mouse liver

The present study aims at revealing the fate of 40-nm gold nanoparticles after intravenous injections. The gold nanoparticles were traced histochemically with light and transmission electron microscopy using autometallographic (AMG) staining, and the gold content in the liver was determined with inductively coupled plasma mass spectrometry (ICP-MS). Gold nanoparticles were identified in almost all Kupffer cells one day after the injection, but the fraction of gold-loaded cells gradually decreased to about one fifth after 6 months. Transmission electron microscopic analysis showed that the gold nanoparticles had accumulated inside the vesicular lysosome/endosome-like structures of the macrophages. At day 1, about 4.5‰ of the area of the liver sections was AMG-stained, after 1 month it had decreased to 0.7‰, and thereafter no further significant reduction was recorded. Because ICP-MS only showed a 9% fall in the gold content over the observed 6 months, the AMG finding of a significant reduction in the stained area of the liver sections and number of macrophages loaded with gold nanoparticles reveals that over time an increasing part of the total amount of gold nanoparticles in the liver is contained in fewer macrophages accumulated in growing clusters.     

Increased postoperative peritoneal adhesion formation after the treatment of experimental peritonitis with chlorhexidine

Background and aims Chlorhexidine is known as a substance that produces adhesions. However, in an experimental model of peritoneal injury, lavage with chlorhexidine and saline solutions produced a similar number of adhesions. This study was designed to test the hypothesis that chlorhexidine gluconate 0.05% solution used for the treatment of peritonitis increases formation of postoperative peritoneal adhesions as compared to standard lavage with saline solution.Material and methods Forty Wistar rats were randomly allocated to gastric or faecal peritonitis groups. In each group rats were further randomly subdivided into saline or chlorhexidine peritoneal lavage groups. After 30 days the rats were killed and intraperitoneal adhesions were evaluated by adhesion score and grading.Results Adhesion scores were statistically significantly different between saline and chlorhexidine groups in both gastric and faecal peritonitis models. In the faecal peritonitis chlorhexidine group a 20% small bowel intussusception rate was observed, while there were no such complications in the other study groups. The conglomerate of organs formed by dense adhesions was present in 60% of cases when gastric peritonitis was lavaged by chlorhexidine and in only 10% when saline solution was used (P<0.05). Neither chlorhexidine nor saline solutions have caused such dense adhesions in faecal peritonitis.Conclusion Peritoneal lavage with chlorhexidine gluconate 0.05% solution in the treatment of experimental peritonitis results in increased adhesion formation.