Comparison of toxic effects of iron-molybdenum polyoxometalates and mixture of their components

Introduction. The physicochemical properties and the impact on living organisms of nanoparticles and components that make up nanoparticles may differ radically, however, insufficient attention is paid to a comparative study of the toxicity of nanoparticles and constituents of nanoparticles. Material and methods. Biochemical and hematological parameters in the blood of 50 male Wistar rats were determined after a single, seven-fold and thirty-fold intramuscular injection of an aqueous solution of iron-molybdenum nanocluster polyoxometalates (POM) and a mixture of the POM components at a dose of 1.5 mg/kg. A solution of a POM components’ mixture was obtained by the destruction of POM with an increase in pH, followed by neutralization, since POM are unstable in an alkaline medium. Results. The introduction of POM did not cause deviations from the norm in the activity of AST, ALT, total alkaline phosphatase and its bone isoenzyme, α-amylase, protein content, urea and creatinine, which indicates the absence of cytolytic syndrome, including in the liver and myocardium, no damage to the acinar part of pancreas, changes in bone tissue, preservation of the protein-synthetic function of the liver and the filtering ability of the kidneys. The introduction of a solution of POM components (molybdenum, iron) was accompanied by an increase in the activity of AST, alkaline phosphatase, the AST / ALT ratio after 7 injections and an increase in the last two parameters after 30 injections. The impact of POM is characterized by an increase in the content of hemoglobin and erythrocytes in the blood and less pronounced leukopenia, in contrast to the mixture of POM components. Conclusion. A less pronounced deviation from the norm of biochemical parameters and a lower degree of leukopenia make it possible to assess the effect of POM nanoparticles as less toxic than the action of POM components not organized into nanoparticles.

The Reserve/Maximum Capacity of Melatonin’s Synthetic Function for the Potential Dimorphism of Melatonin Production and Its Biological Significance in Mammals

In this article, we attempt to classify a potential dimorphism of melatonin production. Thus, a new concept of “reserve or maximum capacity of melatonin synthetic function” is introduced to explain the subtle dimorphism of melatonin production in mammals. Considering ASMT/ASMTL genes in the pseudoautosomal region of sex chromosomes with high prevalence of mutation in males, as well as the sex bias of the mitochondria in which melatonin is synthesized, we hypothesize the existence of a dimorphism in melatonin production to favor females, which are assumed to possess a higher reserve capacity for melatonin synthesis than males. Under physiological conditions, this subtle dimorphism is masked by the fact that cells or tissues only need baseline melatonin production, which can be accomplished without exploiting the full potential of melatonin’s synthetic capacity. This capacity is believed to exceed the already remarkable nocturnal increase as observed within the circadian cycle. However, during aging or under stressful conditions, the reserve capacity of melatonin’s synthetic function is required to be activated to produce sufficiently high levels of melatonin for protective purposes. Females seem to possess a higher reserve/maximum capacity for producing more melatonin than males. Thus, this dimorphism of melatonin production becomes manifest and detectable under these conditions. The biological significance of the reserve/maximum capacity of melatonin’s synthetic function is to improve the recovery rate of organisms from injury, to increase resistance to pathogen infection, and even to enhance their chances of survival by maximizing melatonin production under stressful conditions. The higher reserve/maximum capacity of melatonin synthesis in females may also contribute to the dimorphism in longevity, favoring females in mammals.

Porto-Sinusoidal Vascular Disease and Focal Nodular Hyperplasia-like Nodules in a Patient with Neurofibromatosis and Non-Cirrhotic Portal Hypertension

Introduction/Objective Non-cirrhotic portal hypertension (NCPH) is uncommon. The underlying pathophysiology appears to lie at the level of intrahepatic portal veins and sinusoids, hence the term “porto-sinusoidal vascular disease” (PSVD). We report a rare case of PSVD with focal nodular hyperplasia (FNH)-like nodules in a patient with neurofibromatosis type 2 (NF2). Methods/Case Report A 57-year-old male with NF2 and type 2 diabetes, presented with a large variceal bleed requiring blood transfusion and subsequent transjugular intrahepatic portosystemic shunt (TIPS). Imaging showed a nodular liver, presumed to be cirrhosis due to non-alcoholic liver disease. Liver biopsy was not done. Thereafter, he had several episodes of hepatic encephalopathy and TIPS was downsized to prevent recurrences. The patient required liver transplantation for intractable portal hypertension and severe hepatic encephalopathy; his liver synthetic function was near normal and MELD was 11. Portal vein was patent. The explanted liver was micronodular, soft and weighed 946 grams. Unencapsulated nodules, a few mm to 1 cm in size, were present. Microscopically, there was diffuse nodularity in the absence of bridging fibrosis. Thin, incomplete curvilinear fibrous septa were present. There were aberrant veins, hypervascular portal tracts, herniated portal veins and rare occluded portal veins. Trichrome and reticulin stains confirmed architectural abnormalities including nodularity, lack of bridging fibrosis and approximation of portal tracts. Immunohistochemistry for glutamine synthetase accentuated architectural distortion and revealed nodules with FNH-like geographic areas of staining. Results (if a Case Study enter NA) NA Conclusion This is a rare case of NCPH due to PSVD in a patient with NF2. Microscopy suggested incomplete septal cirrhosis (ISC), a pattern associated with both PSVD and regression of fibrosis in a cirrhotic liver. Isolated portal hypertension without loss of synthetic function favors primary PSVD over regression of fibrosis. FNH-like nodules are consistent with regenerative changes caused by localized abnormalities of blood flow.

Liver failure from delayed hepatitis B reactivation in anti-HBc-positive patient following rituximab for B-cell lymphoma

A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 μmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.

Designing Function-Specific Plant Systems for Sustainable Urban Development

Increasingly, architects are embracing “biomorphic urbanism,” a design ideology that takes inspiration from nature to develop more sustainable cities that reduce the environmental impact of urban life. At the moment, plants are incorporated into biomorphic urban designs for conservation or aesthetic reasons. Here, I argue the role of plants in building more sustainable cities can be augmented by integrating plant sciences, ecology, and urban design. I propose that we can develop synthetic Function-Specific Plant Systems (FSPSs) which harness the genetic and metabolic diversity of plants to perform specific services that benefit society and the environment as a whole. FSPSs can contribute to three broad categories of urban life: Urban Landscape and Infrastructure; Biodiversity and the Environment; and Human Health. Across the three categories, FSPSs can be designed to provide nine key services: flood control, soil stabilization, fire control, climate control, water treatment, habitat for endangered flora and fauna, pest control, air purification, and modulation of human immune systems. The plants included in each FSPS are based on several considerations, including (1) functional traits, (2) biogeography, and (3) cultural concerns. In the future, synthetic biology could improve, expand and diversify these services. This approach harnesses plant biodiversity to transform urban spaces while meeting key UN Sustainable Development Goals.

A ZFYVE19 gene mutation associated with neonatal cholestasis and cilia dysfunction: case report with a novel pathogenic variant

Background ZFYVE19 (Zinc Finger FYVE-Type Containing 19) mutations have most recently been associated to a novel type of high gamma-glutamyl transpeptidase (GGT), non-syndromic, neonatal-onset intrahepatic chronic cholestasis possibly associated to cilia dysfunction. Herein, we report a new case with further studies of whole exome sequencing (WES) and immunofluorescence in primary cilia of her cultured fibroblasts which confirm the observation. Results A now 5-year-old girl born to clinically healthy consanguineous Moroccan parents was assessed at 59 days of life due to severe cholestatic jaundice with increased serum bile acids and GGT, and preserved hepatocellular synthetic function. Despite fibrosis/cirrhosis and biliary ducts proliferation on liver biopsy suggested an extrahepatic biliary obstacle, normal intra-operatory cholangiography excluded biliary atresia. Under choleretic treatment, she maintained a clinically stable anicteric cholestasis but developped hyperlipidemia. After exclusion of the main causes of cholestasis by multiple tests, abnormal concentrations of sterols and WES led to a diagnosis of hereditary sitosterolemia (OMIM #618666), likely unrelated to her cholestasis. Further sequencing investigation revealed a homozygous non-sense mutation (p.Arg223Ter) in ZFYVE19 leading to a 222 aa truncated protein and present in both heterozygous parents. Immunofluorescence analysis of primary cilia on cultured skin fibroblasts showed a ciliary phenotype mainly defined by fragmented cilia and centrioles abnormalities. Conclusions Our findings are consistent with and expands the recent evidence linking ZFYVE19 to a novel, likely non-syndromic, high GGT-PFIC phenotype with neonatal onset. Due to the possible role of ZFYVE19 in cilia function and the unprecedented coexistence of a coincidental hereditary sterol disorder in our case, continuous monitoring will be necessary to substantiate type of liver disease progression and/or possible emergence of a multisystemic involvement. What mentioned above confirms that the application of WES in children with undiagnosed cholestasis may lead to the identification of new causative genes, widening the knowledge on the pathophysiology.

Prediction and prevention of postoperative intra-abdominal adhesive complications in children

The aim of this work was to study the morphology of adhesion formation under the influence of ozone in the experiment, as well as the development of prediction criteria and methods for correcting increased adhesion in children.Materials and methods. Experimental studies were carried out on 36 rabbits «Shinshilla» with a body weight of 0.7–1.2 kg., of which 12 animals were included in the control group, which did not carry out ozonation of the abdominal cavity. The main group consisted of 24 rabbits, which were divided into two subgroups (12 animals in each subgroup), which ozonized the abdominal cavity with an ozone-oxygen mixture. In order to study the prognostic value of the acetylation phenotype in the formation of intraperitoneal adhesions, 67 children with symptoms of adhesive intestinal obstruction were examined.Results. The results of experimental studies showed that in animals of the control group there was the formation of massive adhesions. The basis of adhesions is connective tissue with a significant number of fibroblasts, blood vessels and collagen fibers. In animals of the main group, sharp inhibition of adhesion formation, a delay in the differentiation of fibroblasts and inhibition of their synthetic function were revealed. Acetylation phenotype was determined in 58 patients with appendicular peritonitis. 30 (51%) children turned out to be slow acetylators, and in 28 (49%) patients the phenotype of fast acetylation was established. The results of the study allowed us to isolate fast acetylators as a risk group for excessive adhesion formation and timely start therapeutic and preventive measures.

O67: PERFUSATE GLUCOSE REFLECTS TISSUE GLYCOGENATION DURING LIVER PERFUSION

Introduction Normothermic machine perfusion (NMP) is a method of organ preservation that aims to replicate the physiological environment, achieved by perfusing the livers with a blood-based perfusate at physiological inflow pressures and temperature. NMP also permits viability assessment through evaluation of the perfusate flow rates through the portal vein and hepatic artery. In addition to this, biochemical assessment and perfusate gas analysis can be performed to provide insights into the metabolic activity of the liver. Method Discarded human liver grafts (n=6), were perfused for 24 hours. Core biopsies and perfusate samples were taken from each liver at 5 distinct time intervals over 24 hours. Core biopsies were fixed and stained with periodic acid-Schiff and analysed with Leica software to provide a quantitative estimate of the hepatocellular glycogen content. Result Hepatic glycogen concentration rose during the first hour, followed by a steady decline thereafter until the end of perfusion. Contrary to our initial hypothesis that glucose concentration within the circuit would show an inverse relationship to glycogen stores in the liver cells, we found that glucose concentration closely followed the same trend. Conclusion Change in hepatocyte glycogen content provides an important insight into the synthetic function of a liver destined for transplant. Our research suggests that glucose concentration can be used as a surrogate marker for the synthetic function of a liver on NMP and provides valuable information on the glycogen-synthesising capability of the hepatocytes. In future, this could potentially aid the decision-making process with regards to liver graft transplant viability. Take-home message Perfusate glucose concentration could provide an insight into the viability of liver transplants

Assessment of albumin and aspartate levels as a simple indicator of the efficacy of cryopreservation

<p class="abstract"><strong>Background:</strong> The process of hepatocytes cryopreservation is standardised by most of the laboratories. However there is a variation with respect to the Protocols, media and equipments used amongst the laboratories. Similarly, the tests available to evaluate the efficacy also varies. They are expensive and sometimes might not measure the parameter required for a particular research study. Hence we propose a methodology to study the few basic parameters like cell viability, synthetic function of the cell and cell stability. We have also used a simple percentile calculation to know the efficacy of cryopreservation. This shall help in functional validation of the cell after cryopreservation. The same can also be used to compare the quality of hepatocytes between different batches. The objective of the study was to characterisation of the cells to determine the efficacy of cryopreservation.</p><p class="abstract"><strong>Methods:</strong> Two step collagen isolation method was used to isolate the hepatocytes. Initial cell viability was calculated. A sample of cells were taken for characterisation and the remaining cells cryopreserved. The sample cells were divided into two batches one for pre cryopreservation culture and the other for post cryopreservation. The pre cryopreservation culture was done on monolayer using collagen coated 6 well plate. The other sample was placed in the cryovials for cryopreservation for 1week. After 1 week the cryopreserved cells were thawed and the post cryopreservation viability calculated, followed by post cryopreservation culture. During the process of culture (both pre cryopreservation and post cryopreservation) for 5days Albumin was measured daily and average calculated, peak Aspartate (AST) at 24 hours was recorded. The percentile difference of the obtained values between the pre cryopreservation and post cryopreservation culture was calculated.</p><p class="abstract"><strong>Results:</strong> A total of 12 specimen were enrolled for the study. The mean pre cryopreservation viability of the cells was 66.58%. The post cryopreservation, viability of the cells was 36.43%. The mean difference was -30.170%. The pre cryopreservation albumin values had a mean of 150ng/ml. The post cryopreservation albumin values had a mean of 135.83ng/ml. The mean difference was -14.170ng/ml. The pre cryopreservation peak Aspartate values had a mean of 234.17 IU/ml. The post cryopreservation peak aspartate values had a mean of 230 IU/ml. The mean difference was -4.176 IU/ml.</p><p class="abstract"><strong>Conclusions:</strong> This simple method can validate the cells after cryopreservation by measurement of cell viability, synthetic function of the cell and cell stability.</p><p> </p>

Synthetic Function and Regulation of Osteoblasts: Current Knowledge and Applications

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