Role of red cell sorbitol as determinant of reduced erythrocyte filtrability in insulin-dependent diabetics

Summary Erythrocyte deformability measured as filtration index is clearly diminished in diabetics, thus possibly contributing to diabetes-associated microvascular complications. Moreover, the erythrocyte sorbitol level in IDD is clearly higher than that of non-diabetics, suggesting an alteration in the polyol pathway as possible determinant of diabetes-associated complications. Following this line of research, intracellular sorbitol as well as glucose, inositol, galactitol, mannitol and 2,3-diphosphoglycerate have been studied in 21 diabetics and in 14 controls matched for age and sex. In addition to confirming the high levels of intraerythrocytic glucose and sorbitol in diabetic subjects, statistically significant correlations have been demonstrated between sorbitol and filtration index, between plasma glucose, intracellular glucose level and glycosylated hemoglobin, suggesting a relationship between metabolic control and hemorheologic alterations in diabetes.     

Metabolic bifunctionality of Rv0812 couples folate and peptidoglycan biosynthesis in Mycobacterium tuberculosis

Comparative sequence analysis has enabled the annotation of millions of genes from organisms across the evolutionary tree. However, this approach has inherently biased the annotation of phylogenetically ubiquitous, rather than species-specific, functions. The ecologically unusual pathogen Mycobacterium tuberculosis (Mtb) has evolved in humans as its sole reservoir and emerged as the leading bacterial cause of death worldwide. However, the physiological factors that define Mtb’s pathogenicity are poorly understood. Here, we report the structure and function of a protein that is required for optimal in vitro fitness and bears homology to two distinct enzymes, Rv0812. Despite diversification of related orthologues into biochemically distinct enzyme families, rv0812 encodes a single active site with aminodeoxychorismate lyase and D–amino acid transaminase activities. The mutual exclusivity of substrate occupancy in this active site mediates coupling between nucleic acid and cell wall biosynthesis, prioritizing PABA over D-Ala/D-Glu biosynthesis. This bifunctionality reveals a novel, enzymatically encoded fail-safe mechanism that may help Mtb and other bacteria couple replication and division.     

What Happens at a Dental Surgery When the Patient is a Child with Autism Spectrum Disorder? An Italian Study

Oral health care can be a difficult experience for a child with Autism Spectrum Disorder (ASD), for their family and for the dentist. The purpose of this study is to provide an understanding of the challenges experienced by the three aforementioned figures during oral care treatment. A cohort of 275 parents of typical development children (TD), 57 parents of children with ASD (3–15 years old) and by 61 dentists, completed two different multiple choices questionnaires. The data obtained show a great difficulty in the treatment of children with ASD as seen by the dentists and by the parents. This is due to: caregivers’ demographic issues; difficulties encountered before and during the dental examination; scarce presence of experts in ASD treatment.

     

The Role of Complement in Pregnancy and Fetal Loss

In the United States, between 1 and 3% of women suffer recurrent miscarriages; 50-70% of all conceptions fail. [1,2] Although in the majority of affected women the cause of recurrent miscarriages is unknown, an immune mechanism involving the inappropriate and subsequently injurious recognition of the conceptus by the mother's immune system has been proposed. Murine models have recently been developed that are relevant to this issue. We and others have identified a novel role for complement as an early effector in the pathway leading to pregnancy loss associated with placental inflammation. Indeed, it appears that inhibition of complement activation is an absolute requirement for normal pregnancy, and that in the antiphosphospholid syndrome overwhelming activation of complement triggered by antibodies (Ab) deposited in placenta leads to fetal injury. Identification of complement activation as a mediator of pregnancy loss and definition of the complement components necessary to trigger such injury is likely to lead to a better understanding of its pathogenesis and to new and improved treatments.     

Influence of weight status at 2 years on memory performance at 4–5 years of age

Background: Memory performance is a cognitive function that is affected by environmental, genetic and socioeconomic factors, as well as by weight status.

Aim: To evaluate the association of weight status at 2?years of age with the memory performance of children at 4–5?years of age.

Subjects and methods: A cross-sectional study that used baseline data (2012) and data from two follow-up periods (2014 and 2016) of the PREDI Cohort Study. Participants were mother–child pairs 4–5?years after delivery who were seen between July 2016 and August 2017. The children’s memory performance was evaluated individually using a validated Brazilian instrument.

Results: Of the 203 children included in the study, 117 (57.6%), 52 (25.6%) and 34 (16.8%) had low, moderate and high memory performance, respectively. After adjusting for potential confounders, children with a BMI > 85th percentile had 3.33-times higher odds of exhibiting lower memory performance at 4–5?years of age than those with a BMI ≤ 85th percentile. In addition to the children’s BMI at 2?years of age, mother’s education was another independent determinant of children’s memory performance. There was a progressive increase in the odds of children having lower memory performance at 4–5?years of age as the mother’s education decreased.

Conclusion: Primary prevention of overweight and management of cognitive functions may be important strategies to improve the cognitive development of children in the future.     

Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR−/−)

BackgroundAtherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors.MethodsAnimals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses.ResultsNo changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly.ConclusionsThe results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis.     

Access to original canal trajectory after deviation and perforation with guided endodontic assistance

Procedural accidents are eventualities that may occur during endodontic treatment because of lack of attention to detail or even unforeseeable situations. Knowledge of the root canal anatomy and its variations is a prerequisite for successful endodontic treatment. This case report describes an endodontic treatment where there was an intercurrence, generating deviation and perforation, which was solved with the aid of guided endodontics. A 37 years old, ASA1, was referred to the clinic for localisation and treatment of a calcified canal of the second right upper premolar. The tomographic images revealed the presence of only one canal and deviation with apical perforation. With the help of CBCT and CAD/CAM, it was possible to perform the guided access technique even after deviation and root perforation. Once again, this technique proved to be safe and predictable, allowing for a favourable prognosis in the long term.     

Improving bonding to eroded dentin by using collagen cross-linking agents: 2 years of water storage

Clinical Oral Investigations - The aim of this study was to investigate the effects of collagen cross-linking agents on nanomechanical and bonding properties of eroded dentin (ED), 24 h...     

Mitigation of Cd toxicity by Mn in young plants of cacao,evaluated by the proteomic profiles of leaves and roots

Cd is a non-essential metal and highly toxic to plants, animals and humans, even at very low concentrations. Cd has been found in cocoa beans and in their products, as in the case of chocolate. Mn plays an important role in photosynthetic and can interact with Cd and attenuate its toxic effects on plants. The objective of this work was to evaluate the mechanisms of Mn response in the mitigation of Cd toxicity in young plants of the CCN 51 cacao genotype submitted to 0.8?mmol?Cd kg^?1, 1.6?mmol Mn kg^?1 or the combination of 0.4?mmol?Cd kg^?1?+?0.8?mmol Mn kg^?1 soil, together with the control treatment (without addition of Cd and Mn in soil), by means of analysis of changes in the profile of exclusive proteins (EP) and differentially accumulated proteins (DAP). Leaf and root proteins were extracted and quantified from the different treatments, followed by proteomic analysis. About eight DAP and 38 EP were identified in leaves, whereas in roots 43 DAP and 21 EP were identified. Some important proteins induced in the presence of Cd and repressed in the presence of Cd?+?Mn or vice versa, were ATPases, isoflavone reductase, proteasome and chaperonin. It was concluded that proteins involved in oxidoreduction and defense and stress response processes, in addition to other processes, were induced in the presence of Cd and repressed in the presence of Cd?+?Mn. This demonstrated that Mn was able to mitigate the toxic effects of Cd on young plants of the CCN 51 cocoa genotype.