Excessive BMI is associated with higher C-peptide level at recognition but also with its greater loss in two years clinical observation in children with new onset type 1 diabetes

IntroductionThe prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual β-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation.MethodsWe assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and β-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients’ levels of selected inflammatory cytokines at baseline.ResultsSubjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS <1 and BMI-SDS >1 groups and were significantly higher within BMI-SDS >1 group.DiscussionHigher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual β-cell function. The process seems to be mediated by inflammatory cytokines

AlkB dioxygenase preferentially repairs protonated substrates: specificity against exocyclic adducts and molecular mechanism of action.

Efficient repair by AlkB dioxygenase of exocyclic DNA adducts: 3,N(4)-ethenocytosine, 1,N(6)-ethenoadenine, 3,N(4)- α-hydroxyethanocytosine and, reported here for the first time, 3,N(4)- α-hydroxypropanocytosine, requires higher Fe(II) concentration than the reference 3-methylcytosine. The pH optimum for the repair follows the order of pK(a) values for protonation of the adduct suggesting that positively charged substrates favorably interact with the negatively charged carboxylic group of Asp135 side-chain in the enzyme active centre. This interaction is supported by molecular modeling indicating that 1,N(6)-ethenoadenine and 3,N(4)-ethenocytosine are bound to AlkB more favorably in their protonated cationic forms. An analysis of the pattern of intermolecular interactions that stabilize the location of the ligand points to a role of Asp135 in recognition of the adduct in its protonated form. Moreover, also ab initio calculations underline the role of substrate protonation in lowering the free energy barrier of the transition state of epoxidation of the ethenoadducts studied. The observed time-courses of repair of racemic mixtures of 3,N(4)- α-hydroxyethanocytosine or 3,N(4)- α-hydroxypropanocytosine are unequivocally two-exponential, indicating that the respective stereoisomers are repaired by AlkB with different efficiencies. Molecular modeling of these adducts bound by AlkB allowed evaluation of the participation of their possible conformational states in the enzymatic reaction

Assessment of Serum Concentrations of Ghrelin, Obestatin, Omentin-1, and Apelin in Children with Type 1 Diabetes

The increasing knowledge on the functions of gastric peptides and adipokines in the body allows the assumption of their major role linking the process of food intake, nutritional status, and body growth, largely through the regulation of glucose metabolism and insulin resistance. The aim of the study was the assessment of serum levels of selected gastric peptides and adipocytokines in children with type 1 diabetes, with respect to the disease duration. The study involved 80 children aged 4–18 years (M/F -37/43). Children with type 1 diabetes (n=46) were compared to the control group (n=34). The study group was divided into 4 subgroups: (I) patients with newly diagnosed type 1 diabetes, after an episode of ketoacidosis (n=10), (II) patients with type 1 diabetes of duration no longer than 5 years (n=9), (III) patients with 5 to 10 years of DT1 (n=20), and (IV) patients with type 1 diabetes of duration longer than 10 years (n=7). The concentrations of gastric peptide and adipocytokines across all subgroups were lower than in the control group. The differences were statistically significant (p<0.0001), which may be of importance in the development of the disease complications

Dual catalytic role of the metal ion in nickel-assisted peptide bond hydrolysis

In our previous research we demonstrated the sequence specific peptide bond hydrolysis of the R1-(Ser/Thr)- Xaa-His-Zaa-R2 in the presence of Ni(II) ions. The molecular mechanism of this reaction includes an N–O acyl shift of the R1 group from the Ser/Thr amine to the side chain hydroxyl group of this amino acid. The proposed role of the Ni(II) ion is to establish favorable geometry of the reacting groups. In this work we aimed to find out whether the crucial step of this reaction – the formation of the intermediate ester – is reversible. For this purpose we synthesized the test peptide Ac-QAASSHEQA-am, isolated and purified its intermediate ester under acidic conditions, and reacted it, alone, or in the presence of Ni(II) or Cu(II) ions at pH 8.2. We found that in the absence of either metal ion the ester was quickly and quantitatively (irreversibly) rearranged to the original peptide. Such reaction was prevented by either metal ion. Using Cu(II) ions as CD spectroscopic probe we showed that themetal binding structures of the ester and the final amine are practically identical. Molecular calculations of Ni(II) complexes indicated the presence of steric strain in the substrate, distorting the complex structure from planarity, and the absence of steric strain in the reaction products. These results demonstrated the dual catalytic role of the Ni(II) ion in this mechanism. Ni(II) facilitates the acyl shift by setting the peptide geometry, and prevents the reversal of the acyl shift, by stabilizing subsequent reaction products

The impact of synthetic analogs of histidine on copper(II) and nickel(II) coordination properties to an albumin-like peptide. Possible leads towards new metallodrugs.

The purpose of our research was to obtain peptidomimetics possessing Cu(II) and Ni(II) binding properties, which would be useful for biomedical applications. In this context we used potentiometry, UV-VIS and CD spectroscopies to characterize the Cu(II) and Ni(II) binding properties of pentapeptide analogs of the N-terminal sequence of histatin 5. The peptides investigated had a general sequence DSXAK-am (am stands for C-terminal amide), with X including His and its three synthetic analogs, (4-thiazolyl)-L-alanine (1), (2-pyridyl)-L-alanine (2), and (pyrazol-1-yl)-L-alanine (3). The heterocyclic nitrogens present in these analogs were significantly more acidic than that of the His imidazole. We found that DSXAK-am peptides were able to bind Cu(II) and Ni(II) and form 4N complexes in a cooperative fashion, with similar affinities. These results indicate that acidic heterocyclic amino acids provide a viable alternative for histidine in peptidomimetics designed for metal ion binding

Selected methods of rehabilitation in systemic sclerosis

Systemic sclerosis is a chronic connective tissue disease characterized by microvascular abnormalities, immune disturbances and progressive fibrosis of the skin and internal organs. Skin involvement may result in contractures, leading to marked loss of hand mobility, adversely affecting the performance of daily activities and decreasing the quality of life. Face involvement not only causes functional loss, but also lowers the self-esteem of patients. Increasing attention has recently been focused on the need to rehabilitate patients with systemic sclerosis in order to prevent the development of joint contractures and loss of mobility. The study presents a review of the current literature on rehabilitation possibilities in patients with systemic sclerosis, with a special focus on physiotherapy methods

Mikrobiologiczna i chemiczna ocena jakości małych rzek uchodzących do Południowego Bałtyku. Część II : Analiza cieków wodnych w zlewni Zatoki Puckiej

Due to its location, Puck Bay is an area particularly vulnerable to pollution of anthropogenic origin. The aim of the study was to assess the water quality of small watercourses entering the inner part of Puck Bay. The paper presents the results of chemical and microbiological analyses of 10 rivers and canals at their estuaries located on the western shore of the internal Puck Bay. The following environmental parameters were analyzed: conductivity, pH, dissolved oxygen concentration (in situ measurements), COD (cuvette tests), concentrations of ions (ion chromatography). Microbiological analysis included assessment of sanitary condition based on the number of fecal coliforms by a cultivation method. The determination of basic microbiological parameters such as: prokaryotic cell abundance expressed as total cells number (TCN), prokaryotic cell biovolume expressed as average cell volume (ACV), the prokaryotic biomass (PB) and prokaryotic cell morphotype diversity were determined using epifluorescence microscopy method. Based on the obtained results, it was found that small watercourses may carry a notable load of anthropogenic pollution and thus affect the environment of Puck Bay. The results clearly indicate the need for quality monitoring in the rivers and canals in the Coastal Landscape Park, flowing into Puck Bay. The research showed that also smaller watercourses may have an impact on the coastal waters’ state, and thus on the Baltic Sea water quality.Zatoka Pucka, ze względu na swoje położenie, jest obszarem szczególnie narażonym na zanieczyszczenia pochodzenia antropogenicznego. Celem pracy była ocena jakości wód małych cieków wodnych uchodzących do wewnętrznej części Zatoki Puckiej. W pracy przedstawiono wyniki analiz chemicznych i mikrobiologicznych 10 rzek i kanałów w ujściach zlokalizowanych na zachodnim brzegu wewnętrznej Zatoki Puckiej. Analizie poddano następujące parametry środowiskowe: przewodność, pH, stężenie tlenu rozpuszczonego (pomiary in situ), ChZT (testy kuwetowe), stężenie jonów (chromatografia jonowa). Analiza mikrobiologiczna obejmowała ocenę stanu sanitarnego na podstawie liczby bakterii grupy coli typu kałowego metodą hodowlaną. Oznaczenia parametrów mikrobiologicznych takich jak: liczebność komórek prokariotycznych, średnia objętość komórek, biomasa oraz zróżnicowanie morfotypowe komórek prokariotycznych określono metodą mikroskopii epifluorescencyjnej. Na podstawie uzyskanych wyników stwierdzono, że małe cieki mogą przenosić znaczny ładunek zanieczyszczeń antropogenicznych i tym samym wpływać na środowisko Zatoki Puckiej. Uzyskane wyniki jednoznacznie wskazują na potrzebę prowadzenia monitoringu jakości rzek i kanałów w Nadmorskim Parku Krajobrazowym uchodzących do Zatoki Puckiej. Z badań wynika, że również mniejsze cieki mogą mieć wpływ na stan wód przybrzeżnych, a tym samym na jakość wód Morza Bałtyckiego

Effect of d‑Amino Acid Substitutions on Ni(II)-Assisted Peptide Bond Hydrolysis

Previously we demonstrated the sequence-specific hydrolysis of the R₁-(Ser/Thr)-peptide bond in Ni­(II) complexes of peptides with a general R₁-(Ser/Thr)-Xaa-His-Zaa-R₂ sequence (R₁ and R₂ being any sequences) (Kopera, E.; Krezel, A.; Protas, A. M.; Belczyk, A.; Bonna, A.; Wyslouch-Cieszynska, A.; Poznanski, J.; Bal, W. <i>Inorg. Chem</i>. <b>2010</b>, <i>49</i>, 6636). In order to refine our understanding of the mechanism of this reaction and to find ways to accelerate it, we undertook a systematic study of effects of d-amino acid substitutions in the template Ac-Gly-Ala-Ser-Arg-His-Trp-Lys-Phe-Leu-NH₂ peptide on the hydrolysis rate constants. We found that all stereochemical alterations made around the Ni­(II) chelate plane resulted in the decrease of the reaction rate. However, the Ni­(II) coordination, a prerequisite to the reaction, was not compromised by these substitutions. We demonstrated that the reaction is only possible when either the side chain of the crucial Ser (or Thr) residue is on the same part of the chelate plane as the next residue in the sequence (Arg), or the side chain of the residue following His (Trp) resides on the opposite side of the plane. The rate of reaction is the fastest when both these conditions are fulfilled. Another novel effect is the strong dependence of the rate of the acyl shift step on the character of the leaving group

Microbial and chemical quality assessment of the small rivers entering the South Baltic. Part 1, Case study on the watercourses in the Baltic Sea catchment area

The area of the Coastal Landscape Park (CLP) due to its location is extremely attractive touristic area. In the summer season, a significant increase in population density is observed, which influences surface water quality. Large numbers of tourists generate an increased amount of municipal wastewater, being treated in local treatment plants and discharged into rivers and streams. The paper presents preliminary research from summer 2016 on three watercourses ending in the Baltic Sea: Piaśnica, Karwianka and Czarna Wda rivers. It is a part of a long-term project conducted in CLP to assess surface waters quality. The scope of research included measurements of in situ parameters (temperature, conductivity, pH, dissolved oxygen). Chemical Oxygen Demand was determined using a spectrophotometer. Ion chromatography was used to determine ions concentrations (including biogenic compounds). Sanitary state of watercourses was assessed based on fecal coliforms abundance, which number was determined by the cultivation method. The determination of microbiological parameters such as: prokaryotic cell abundance expressed as total cells number (TCN), prokaryotic cell biovolume expressed as average cell volume (ACV), the prokaryotic biomass (PB) and prokaryotic cell morphotype diversity was determined using epifluorescence microscopy method. Results showed that water quality of Piaśnica and Czarna Wda rivers were affected by discharged treated wastewater. In the case of Karwianka River, the main pollution source could be surface runoff from fields and unregulated sewage management in this area. The conducted research confirmed the urgent need for better protection of this area to conserve both its ecosystem and value for tourism