Maternal and Neonatal Outcome of Pregnancies with Autoimmune Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune neuromuscular disease manifested by the weakness and fatigue in skeletal muscles of the face and extremities. Transient neonatal myasthenia gravis is an uncommon type of MG affecting the newborns with mothers who suffer from the disorder or specific circulating autoantibodies. In most cases, the intensity of transient neonatal MG is not associated with the mothers’ condition but rather with maternal antibody titers. The symptoms of transient neonatal MG are hypotonia, feeding difficulties, weak cry, facial diplegia, and breathing difficulties in the affected newborns. The disease is connected to the passive transplacental transfer of anti-acetylcholine receptor antibodies (anti-AChR) or antimuscle-specific tyrosine kinase antibodies (anti-MuSK) from the affected mother to the infant. The postsynaptic neuromuscular junction is damaged by the circulation of autoimmune antibodies, and the antibodies directed against fetal AChR are responsible for the form of fetal onset. Monitoring of these newborns is necessary in the first 7 days upon birth, since during this period of life, TNM symptoms can be detected, especially on the second day. In pregnancy period, myasthenia gravis symptoms may vary and they frequently worsen, sometimes leading to premature delivery

Placenta Abruption and Delivery Method

Placental abruption is a significant contributor to maternal mortality worldwide. Early and skilled medical intervention is needed to ensure a good outcome, and this is not available in many parts of the world. Abruptio placentae are defined as the premature separation of the placenta from the uterus. Placental abruption must be considered whenever bleeding is encountered in the second half of pregnancy, since it is a significant cause of third-trimester bleeding associated with fetal and maternal morbidity and mortality. If the bleeding persists, fetal and maternal distress may develop. Fetal and maternal death may occur if appropriate interventions are not undertaken. The severity of fetal distress correlates with the degree of placental separation. In near-complete or complete abruption, fetal death is inevitable unless an immediate cesarean delivery is undertaken

Significance of Lipid and Lipoprotein in Organism

Lipids are important energy and building compounds. Their decomposition provides a significant amount of energy required for various life processes. It can thus be deposited in triglycerides and adipocytes. Some of them, in conjunction with proteins, form the most important structural elements of cells and cellular organelles, while others are precursors for the synthesis of numerous active compounds such as some hormones or prostaglandins. Lipids are ingested but can also be synthesized in the body. In circulation, lipids are found packed in lipoprotein molecules because they are insoluble in water. Lipoproteins have a central lipid part (nucleus) containing triglycerides and cholesterol esters, and on the surface there is a sheath composed of certain proteins (apoproteins), phospholipids, and small amounts of free cholesterol. Thanks to this sheath, lipids can be transported via blood. It took a long time to determine the importance and role of lipids in the body, as well as their role in many metabolic disorders of various diseases. This field is still unexplored and is a challenge for many researchers to prevent and treat lipid metabolism disorders

Relationships Between Bone Treatment Conditions and Co2+ Sorption Capacities

Co-60 is an important radionuclide in spent nuclear fuel and liquid radioactive wastes. For the purification of water containing Co2+, ions sorption on hydroxyapatite (Ca-10(PO4)(6)(OH)(2)) can be applied. The process is particularly cost-effective if biological apatite from animal bones is utilized. In this study, dependence between bovine bone treatment conditions and Co2+, sorption was investigated as a function of initial metal concentration. Eight sorbents were previously prepared using fractional factorial design, by simultaneous variations of five process variables between two levels: factor A-the type of the chemical reagent (H2O2 or NaOH), factor B-reagent concentration (0.1 mol/L or 2 mol/L), factor C-reaction temperature (20(o)C or 60(o)C), factor D-contact time (1h or 3h) and factor E-sample annealing (without or at 400(o)C). At this point, the effects of treatment factors on Co2+, sorption efficiency were evaluated using statistical analysis. Amounts of Co2+ sorbed, amounts of released Ca2+ ions and final pH values were considered as system responses. The results showed that the impact of various treatment factors was different for different starting concentrations of Co2+. Consequently, no statistically important relations could be established between treatment conditions and Co2+, sorption from 10(-4) and 5*10(-4) mol/L solutions, whereas thermal treatment at 400(o)C was the only statistically significant factor influencing sorption from the most concentrated solution (5*10(-3) mol/L). Depending on initial Co2+, concentration, various factors had statistically significant effect on equilibrium pH values, whereas no relation was found between bone treatment conditions and the amounts of Ca2+, released during the sorption.3rd International Conference on Radiation and Applications in Various Fields of Research (RAD), Jun 08-12, 2015, Budva, Montenegr

Kvalitet mleka i osobine surutke dobijene pri proizvodnji Sjeničkog sira u industrijskim uslovima

Sjenica cheese is one of our best kinds of cheese from the group of white cheese in brine. Since the quality and overall value of the cheese depend on the quality and chemical composition of milk, before making cheese it is necessary to determine these parameters. Milk fat content in cow milk was 3.1%, protein 31.3%, dry matter 10.96%, casein 2.85%. Sheep milk of richer chemical composition had a dry matter 8.14%, fat 6.80%, protein 5.97%, casein 20.5%. Chemical composition of whey gauge the validity of keeping the process of making cheese. On the basis of dry matter content (cow whey 5.65% and sheep whey 7.5%), fat (cow whey 0.023%, sheep whey 0.62%), protein (cow whey 0.81% , sheep whey 1.44%), it is seen that the process of producing cheese is well managed with optimal utilization of milk ingredients.Sjenički sir je jedan od naših najboljih sireva iz grupe belih sireva u salamuri. Proizvodi se na individualnim gazdinstvima područja Sjeničko-pešterske visoravni. Sir se proizvodi od svežeg punomasnog kravljeg i očijeg mleka bez termičkog tretmana. Pošto kvalitet i opšte vrednosti sira zavise od kvaliteta i hemijskog sastava mleka , pre izrade sireva neophodno je odrediti te parametre. Sadržaj mlečne masti kod kravljeg mleka bio je 3.1%, proteina 3.31%, suve materije 10.96%, kazeina 2.85%. Ovčije mleko koje je bogatijeg hemijskog sastava imalo je suve materije 18.14%, masti 6.80%, proteina 5.97%, kazeina 5.20%. Na osnovu sadržaja suve materije (5.65% kravlja i 7.05% ovčja ) , masti ( 0.23% kravlja; 0.62% ovčija), proteina ( 0.81% kravlja, 1.44% ovčja), kod surutke vidi se da je proces proizvodnje sireva dobro vođen uz optimalnu iskorišćenost sastojaka mleka

Ni(Ii) Immobilization By Bio-Apatite Materials: Appraisal of Chemical, Thermal and Combined Treatments

Animal bones are a natural and rich source of calcium hydroxyapatite (HAP), which has been found to be a good sorbent material for heavy metals and radionuclides. Various treatments can reduce the content of bone organic phase and improve sorption properties. In this study, sorption capacities of raw bovine bones (B) and samples obtained by chemical treatment with NaOH (B-NaOH), by heating at 400 degrees C (B-400) and by combined chemical and thermal treatment (BNaOH+400), were compared, using Ni(II) ions as sorbates. Maximum sorption capacities increased in the order B LT B-NaOH LT B-400 LT BNaOH+400. Based on different sorption data and FT-IR analyses, the mechanism of Ni(II) sorption was found to be complex, with participation of both HAP and organic phase (when present). Sequential extraction analysis was applied for testing the stability of Ni(II) ions sorbed by BNaOH+400. Majority of Ni(II) was found in residual phase (65%) at lower level of sorbent loading, while with the increase of sorbent saturation carbonate fraction became dominant (39%). According to the results, BNaOH+400 can be utilized in water purification systems. As an apatite based material with low organic content and high efficiency for Ni(II) sorption, it is also a good candidate for in situ soil remediation, particularly at lower contamination levels

Modeling the Structural Consequences of \u3cem\u3eBEST1\u3c/em\u3e Missense Mutations

Mutations in the bestrophin-1 gene (BEST1) are an important cause of inherited retinal disorders. Hitherto, over 100 unique allelic variants have been linked to the human BEST1 (hBEST1), and associated with disease phenotypes, broadly termed as bestrophinopathies. A spontaneous animal model recapitulating BEST1-related phenotypes, canine multifocal retinopathy (cmr), is caused by mutations in the canine gene ortholog (cBEST1). We have recently characterized molecular consequences of cmr, demonstrating defective protein trafficking as a result of G161D (cmr2) mutation. To further investigate the pathological effects of BEST1 missense mutations, canine and human peptide fragments derived from the protein sequence have been studied in silico as models for early events in the protein folding. The results showed that G161D as well as I201T substitutions cause severe conformational changes in the structure of bestrophin-1, suggesting protein misfolding as an underlying disease mechanism. The comparative modeling studies expand our insights into BEST1 pathogenesis

Mislocalisation of BEST1 in iPSC-derived retinal pigment epithelial cells from a family with autosomal dominant vitreoretinochoroidopathy (ADVIRC)

Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare, early-onset retinal dystrophy characterised by distinct bands of circumferential pigmentary degeneration in the peripheral retina and developmental eye defects. ADVIRC is caused by mutations in the Bestrophin1 (BEST1) gene, which encodes a transmembrane protein thought to function as an ion channel in the basolateral membrane of retinal pigment epithelial (RPE) cells. Previous studies suggest that the distinct ADVIRC phenotype results from alternative splicing of BEST1 pre-mRNA. Here, we have used induced pluripotent stem cell (iPSC) technology to investigate the effects of an ADVIRC associated BEST1 mutation (c.704T > C, p.V235A) in patient-derived iPSC-RPE. We found no evidence of alternate splicing of the BEST1 transcript in ADVIRC iPSC-RPE, however in patient-derived iPSC-RPE, BEST1 was expressed at the basolateral membrane and the apical membrane. During human eye development we show that BEST1 is expressed more abundantly in peripheral RPE compared to central RPE and is also expressed in cells of the developing retina. These results suggest that higher levels of mislocalised BEST1 expression in the periphery, from an early developmental stage, could provide a mechanism that leads to the distinct clinical phenotype observed in ADVIRC patients

Interaction of Bestrophin-1 and Ca2+ Channel β-Subunits: Identification of New Binding Domains on the Bestrophin-1 C-Terminus

Bestrophin-1 modulates currents through voltage-dependent L-type Ca2+ channels by physically interacting with the β-subunits of Ca2+ channels. The main function of β-subunits is to regulate the number of pore-forming CaV-subunits in the cell membrane and modulate Ca2+ channel currents. To understand the influence of full-length bestrophin-1 on β-subunit function, we studied binding and localization of bestrophin-1 and Ca2+ channel subunits, together with modulation of CaV1.3 Ca2+ channels currents. In heterologeous expression, bestrophin-1 showed co-immunoprecipitation with either, β3-, or β4-subunits. We identified a new highly conserved cluster of proline-rich motifs on the bestrophin-1 C-terminus between amino acid position 468 and 486, which enables possible binding to SH3-domains of β-subunits. A bestrophin-1 that lacks these proline-rich motifs (ΔCT-PxxP bestrophin-1) showed reduced efficiency to co-immunoprecipitate with β3 and β4-subunits. In the presence of ΔCT-PxxP bestrophin-1, β4-subunits and CaV1.3 subunits partly lost membrane localization. Currents from CaV1.3 subunits were modified in the presence of β4-subunit and wild-type bestrophin-1: accelerated time-dependent activation and reduced current density. With ΔCTPxxP bestrophin-1, currents showed the same time-dependent activation as with wild-type bestrophin-1, but the current density was further reduced due to decreased number of Ca2+ channels proteins in the cell membrane. In summary, we described new proline-rich motifs on bestrophin-1 C-terminus, which help to maintain the ability of β-subunits to regulate surface expression of pore-forming CaV Ca2+-channel subunits

Regulation of Bestrophins by Ca2+: A Theoretical and Experimental Study

Bestrophins are a recently discovered family of Cl− channels, for which no structural information is available. Some family members are activated by increased intracellular Ca2+ concentration. Bestrophins feature a well conserved Asp-rich tract in their COOH terminus (Asp-rich domain), which is homologous to Ca2+-binding motifs in human thrombospondins and in human big-conductance Ca2+- and voltage-gated K+ channels (BKCa). Consequently, the Asp-rich domain is also a candidate for Ca2+ binding in bestrophins. Based on these considerations, we constructed homology models of human bestrophin-1 (Best1) Asp-rich domain using human thrombospondin-1 X-ray structure as a template. Molecular dynamics simulations were used to identify Asp and Glu residues binding Ca2+ and to predict the effects of their mutations to alanine. We then proceeded to test selected mutations in the Asp-rich domain of the highly homologous mouse bestrophin-2. The mutants expressed in HEK-293 cells were investigated by electrophysiological experiments using the whole-cell voltage-clamp technique. Based on our molecular modeling results, we predicted that Asp-rich domain has two defined binding sites and that D301A and D304A mutations may impact the binding of the metal ions. The experiments confirmed that these mutations do actually affect the function of the protein causing a large decrease in the Ca2+-activated Cl− current, fully consistent with our predictions. In addition, other studied mutations (E306A, D312A) did not decrease Ca2+-activated Cl− current in agreement with modeling results