Soluble adhesion molecules ICAM-1, VCAM-1, P-selectin in children with Helicobacter pylori infection

AIM: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children with Helicobacter pylori (H pylori) infection and to evaluate their significance for the morphological changes found in gastric mucosa. METHODS: The study included 106 children: 59 children (55.7%) with chronic gastritis and positive IgG against H pylori, 29 children (27.3%) after previous H pylori infection without the bacterium colonization but with positive IgG against H pylori, and 18 children (17%) with functional disorders of the gastrointestinal system but with normal IgG against H pylori. Endoscopic and histopathological evaluation of gastric mucosa was performed based on the Sydney System classification. The evaluation of sP-selectin, sICAM-1, sVCAM-1 levels in the sera of children was carried out using ELISA test. RESULTS: The assessment of gastritis activity degrees indicated statistically significant values in the antrum and corpus (P＜0.001) of children examined. Serum sVCAM-1 levels were higher in group with gastritis due to H pylori infection than in group without infection and differed statistically (P＜0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive molecules in infected children and decreased after eradication of H pylori. Serum sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were similar in children with and without H pylori infection. CONCLUSION: Assessment of adhesive molecules (sP-selectin, sICAM-1, sVCAM-1) in the sera of children with active H pylori infection can show the participation of sVCAM-1 in the pathogenesis of gastric mucosal inflammation. sP-selectin and sICAM-1 concentrations in the sera of children with H pylori infection after eradication cannot reveal any significant differences as compared to healthy children.     

A nickel–titanium memory-shape device for gastrojejunostomy: comparison of the compression anastomosis clip and a hand-sewn anastomosis

Background

The aim of this study was to evaluate the efficacy of a compression anastomosis clip (CAC) for gastrojejunostomy and comparison of a novel technique with a hand-sewn anastomosis.

Methods

Sixty-six patients underwent gastrojejunostomy with the CAC or hand-sewn anastomosis. The time of bowel function recovery, the duration of nasogastric drainage, the time of initiation of oral feeding, the duration of postoperative hospital stay, the time needed to expel the clip, and the observation of any complications were recorded.

Results

Neither group had anastomotic complications such as leakage or obstruction. Anastomosis time was shorter in the CAC group than in the control group (P < 0.01). The mean time of clip expulsion was 15.1 ± 6.04 d. There was no statistical difference in postoperative results between the two groups. There was a moderate positive correlation between the day of first bowel movement and the day of clip expulsion (r = 0.536) and a strong correlation between the duration of nasogastric drainage and the day of clip expulsion (r = 0.881).

Conclusions

The method of using a CAC appeared to be safe, easy, inexpensive, and less time consuming. It should be taken into consideration that intra-abdominal complications may cause delayed CAC expulsion.     

Structural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein

The nicotinic acetylcholine receptor (nAChR) and the acetylcholine binding protein (AChBP) are pentameric oligomers in which binding sites for nicotinic agonists and competitive antagonists are found at selected subunit interfaces. The nAChR spontaneously exists in multiple conformations associated with its activation and desensitization steps, and conformations are selectively stabilized by binding of agonists and antagonists. In the nAChR, agonist binding and the associated conformational changes accompanying activation and desensitization are cooperative. AChBP, which lacks the transmembrane spanning and cytoplasmic domains, serves as a homology model of the extracellular domain of the nAChRs. We identified unique cooperative binding behavior of a number of 4,6-disubstituted 2-aminopyrimidines to Lymnaea AChBP, with different molecular variants exhibiting positive, n_H > 1.0, and negative cooperativity, n_H < 1.0. Therefore, for a distinctive set of ligands, the extracellular domain of a nAChR surrogate suffices to accommodate cooperative interactions. X-ray crystal structures of AChBP complexes with examples of each allowed the identification of structural features in the ligands that confer differences in cooperative behavior. Both sets of molecules bind at the agonist-antagonist site, as expected from their competition with epibatidine. An analysis of AChBP quaternary structure shows that cooperative ligand binding is associated with a blooming or flare conformation, a structural change not observed with the classical, noncooperative, nicotinic ligands. Positively and negatively cooperative ligands exhibited unique features in the detailed binding determinants and poses of the complexes.Nicotinic acetylcholine receptors (nAChRs) function as allosteric pentamers of identical or homologous transmembrane spanning subunits. Ligand binding at two or more of the five intersubunit sites, located radially in the extracellular domain, drives a conformational change that results in the opening of a centrosymmetric transmembrane channel, internally constructed among the five subunits (SI Appendix, Fig. S2A) (1–4). Up to five potential agonist-competitive antagonist sites on the pentamer are found at the outer perimeter of the subunit interfaces. Amino acid side-chain determinants on both subunit interfaces dictate selectivity among the many subtypes of nAChRs. The interconversion between resting, active, and desensitized states occurs in the absence of ligands, and partial occupation of the binding sites suffices for agonist activation of the receptor and its antagonism (5–7). Cooperativity of agonist association and its coupling to channel gating likely play important roles in the dynamics of nicotinic responses and in sharpening the concentration and temporal windows for activation.As revealed in functional studies, most nAChRs are hetero-oligomeric, where the sites of ligand occupation are not identical (1–4). This arrangement arises when a common α-subunit pairs with one or more nonidentical subunit partners, termed non–α-subunits (7, 8). Nonidentity of the subunit interface complementary to the α-subunit may also give rise to heterogeneity in binding constants typically seen for antagonists and mask partially the degree of agonist cooperativity. An exception to this is the α7-neuronal nAChR composed of five identical subunits and exhibiting a high degree of cooperativity for agonist activation (9). Recently, sequence alignments identified genes coding for pentameric ligand-gated ion channels in prokaryotes led to the resolution of the first structure by X-ray crystallography on 3D crystals of a pentameric receptor protein from Erminia chrysanthemi (ELIC) (10) and Gloeobacter violaceus (GLIC) (11, 12) and provided high-resolution structures of the two end point states of the cooperative gating mechanism in the same pentameric ligand-gated ion channel (GLIC) (13). Recently, the first structure of a eukaryotic member of the family, the anionic glutamate receptor from Caenorhabditis elegans (GluCl), was solved at atomic resolution (14), revealing remarkable identity of 3D structure with GLIC.The acetylcholine binding protein (AChBP) was characterized from mollusks (15–17) and consists of only a homologous extracellular domain of the nAChR. Assembled as a homomeric pentamer, AChBP exhibits a similar profile of ligand selectivity toward the classical nicotinic agonists and antagonists of quaternary amine, tertiary and secondary amine (alkaloid), imine, and peptide origin that bind nicotinic receptors (18–25). If looked at solely on the basis of ligand-binding capacities, AChBP could be considered as a distinct subtype of nAChR. Although its homomeric composition and ligand selectivity best resemble the α7-subtype of nAChR, when the concentration dependence of ligand occupation has been examined, no evidence of cooperativity emerged (21). Accordingly the cooperative behavior for both activation and desensitization of receptors, seen for the classical nicotinic agonists with nAChRs, might arise from a cooperative torsional motion driven by the transmembrane spanning domain of the receptor (26).We demonstrate here a set of ligands that bind to the AChBP in a cooperative fashion, whereby binding to a single subunit affects the binding energy at identical interfaces in the pentamer. Hence, interactions within the extracellular domain of this family of homologous pentameric proteins establish a circumferential linkage between subunit interfaces which results in cooperative behavior.     

Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.     

Kardiomiopatia restrykcyjna – historia ze szczęśliwym zakończeniem

Cardiomyopathies are a group of rare diseases of a myocardium in a pediatric population which affect 1–1.5 cases per 100 000 children. Restrictive cardiomyopathy (RCM) is the least common type, which constitutes 2–5% of all cardiomyopathies. RCM is characterized by a diastolic dysfunction which is a result of an increased stiffness of the ventricular myocardium with a normal systolic function. Differential diagnosis should include especially constrictive pericarditis. Because of a poor prognosis, it is important to diagnose patients as soon as possible and to early qualify them for a heart transplantation.