Antioxidative and Oxidative Profiles in Plasma and Saliva in Dairy Cows during Pregnancy

Increased metabolism that occurs during pregnancy can result in oxidative stress which is harmful to cells and, consequently, for the proper functioning of the whole organism. Plasma and recently also saliva are important resources for evaluating physiological and pathological conditions in animals. The study aimed to investigate the influence of the metabolic state on the effectiveness of the antioxidant profile of plasma and saliva during the pregnancy of cows. Seventy-six healthy pregnant and twelve non-pregnant control cows were included in the study. Blood and saliva samples were collected each month of the pregnancy course. Examined body fluids were used to evaluate both the total antioxidant capacity (TAC) and the oxidative parameters related to protein and lipid peroxidative processes. TAC, the content of hydroperoxides, and SH groups were determined spectrophotometrically while formylokinurenine and bityrosine contents were measured spectrofluorimetrically. The results showed dynamic changes depending on the period of pregnancy course. The highest antioxidant activity in plasma was mostly noted in early pregnancy and advanced pregnant cows. All tested parameters except SH groups expressed higher values in saliva compared to plasma. Obtained results reveal that the increase in oxidative intensity induced appropriate answers of cells reflected in the increase in antioxidative activity of the organism. Moreover, some examined parameters can indicate the intensity of oxidative stress and therefore could be used in a panel of markers of the physiological course of pregnancy. However, with regards to antioxidant/oxidative parameters, saliva reflects the content of plasma only in part, due to the local metabolism of the salivary gland. Further studies are necessary to establish physiological ranges of antioxidative/oxidative profiles in cows and to define the usefulness of saliva as biological material in oxidative stress diagnostics.

Hippocampal Metabolic Subregions and Networks: Behavioral, Molecular and Pathological Aging Profiles

Purpose: Hippocampal dysfunction happens across many neuropsychiatric disorders and is the hallmark of Alzheimer’s disease with evidenced metabolic alterations. However, while metabolic changes are a key aspect of Alzheimer’s disease, hippocampal metabolic networks, as defined by metabolic covariance, haven’t been identified in healthy populations. As the hippocampus portrays cytoarchitectural, connectional, and functional heterogeneity, heterogeneous patterns of metabolic covariance could be expected. Methods: We first characterized this heterogeneity with a data-driven approach by identifying the spatial pattern of hippocampus differentiation based on metabolic covariance with the rest of the brain in FDG-PET data of large healthy elderly cohort (n=362). Then, we characterized the metabolic networks of the robustly defined subregions. In the following, we characterized the disentangled hippocampal metabolic networks with regards to behavioral and neurotransmitter systems using quantitative decoding. Finally, we examined how the local metabolism in the hippocampal subregions is influenced by Alzheimer’s disease pathology in a cohort of ADNI participants (n = 580). Results: Based on hippocampal-brain metabolic covariance in a healthy elderly cohort, we found a differentiation into primarily anterior vs. posterior and secondarily Cornu Ammonis (CA) vs. subiculum subregions. Characterizing the associated metabolic networks revealed that the anterior-subiculum network including temporal-pole and orbitofrontal regions relates to self, motivation and mentalizing behavior and is influenced by dopaminergic systems. In contrast, the posterior-subiculum shows a wide cortical network engaged in action- and world-oriented cognition targeted by serotoninergic systems. The anterior- and posterior-CA, connected respectively to amygdala and broader subcortical networks, are associated to several transporters release. Local metabolism comparison between Alzheimer’s disease-related diagnosis groups revealed early CA’s alterations while posterior subicular alterations appear at advanced stages in line with broader cortical atrophy and behavioral dysfunctions.Conclusion: Future studies should delineate patients’ individual profiles according to hippocampal subregions and networks.

The reason for the formation of pseudoarthrosis by Zondek (Zentr. f. Chir., 1926, No. 20)

The reason for the formation of pseudoarthrosis, no Zondek (Zentr. F. Chir., 1926, No. 20), lies in the violation of general or local metabolism.

Adipocyte dedifferentiation in health and diseases

Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the adipocytes or fat cells, are remarkably plastic and can increase or decrease their size and number to adapt to changes in systemic or local metabolism. Changes in adipocyte size occur through hypertrophy or atrophy, and changes in cell numbers mainly involve de novo generation of new cells or death of existing cells. Recently, dedifferentiation, whereby a mature adipocyte is reverted to an undifferentiated progenitor-like status, has been reported as a mechanism underlying adipocyte plasticity. Dedifferentiation of mature adipocytes has been observed under both physiological and pathological conditions. This review covers several aspects of adipocyte dedifferentiation, its relevance to adipose tissue function, molecular pathways that drive dedifferentiation, and the potential of therapeutic targeting adipocyte dedifferentiation in human health and metabolic diseases.

The analysis of glutamate and glutamine frequencies in human proteins as marker of tissue oxygenation

In this study, we investigated whether the relative abundance of glutamate and glutamine in human proteins reflects the availability of these amino acids (AAs) dictated by the cellular context. In particular, because hypoxia increases the conversion of glutamate to glutamine, we hypothesized that the ratio glutamate/glutamine could be related to tissue oxygenation. By histological, biochemical and genetic evaluation, we identified proteins expressed selectively by distinct cellular populations that are exposed in the same tissue to high or low oxygenation, or proteins codified by different chromosomal loci. Our biochemical assessment was implemented by software tools that calculated the absolute and the relative frequencies of all AAs contained in the proteins. Moreover, an agglomerative hierarchical cluster analysis was performed. In the skin model that has a strictly local metabolism, we demonstrated that the ratio glutamate/glutamine of the selected proteins was directly proportional to oxygenation. Accordingly, the proteins codified by the epidermal differentiation complex in the region 1q21.3 and by the lipase clustering region 10q23.31 showed a significantly lower ratio glutamate/glutamine compared with the nearby regions of the same chromosome. Overall, our results demonstrate that the estimation of glutamate/glutamine ratio can give information on tissue oxygenation and could be exploited as marker of hypoxia, a condition common to several pathologies.

High gastrointestinal permeability and local metabolism of naringenin: influence of antibiotic treatment on absorption and metabolism

The present study aims to determine the permeability of naringenin in the stomach, small intestine and colon, to evaluate intestinal and hepatic first-pass metabolism, and to study the influence of the microbiota on the absorption and disposition of naringenin (3·5 μg/ml). A single-pass intestinal perfusion model in mice (n4–6) was used. Perfusate (every 10 min), blood (at 60 min) and bile samples were taken and analysed to evaluate the presence of naringenin and its metabolites by an HPLC-MS/MS method. To study the influence of the microbiota on the bioavailability of naringenin, a group of animals received the antibiotic rifaximin (50 mg/kg per d) for 5 d, and naringenin permeability was determined in the colon. Naringenin was absorbed well throughout the gastrointestinal tract but mainly in the small intestine and colon (mean permeability coefficient 7·80 (sd1·54) × 10− 4cm/s and 5·49 (sd1·86) × 10− 4cm/s, respectively), at a level similar to the highly permeable compound, naproxen (6·39 (sd1·23) × 10− 4cm/s). According to the high amounts of metabolites found in the perfusate compared to the bile and plasma, naringenin underwent extensive intestinal first-pass metabolism, and the main metabolites excreted were sulfates (84·00 (sd12·14)%), followed by glucuronides (8·40 (sd5·67)%). Phase II metabolites were found in all perfusates from 5 min of sampling. Mice treated with rifaximin showed a decrease in naringenin permeability and in the amounts of 4-hydroxyhippuric acid and hippuric acid in the lumen. Naringenin was well absorbed throughout the gastrointestinal tract and its poor bioavailability was due mainly to high intestinal metabolism.