Humoral and cellular immune responses in children given annual immunization with trivalent inactivated influenza vaccine

BACKGROUND: There have been no prior reports of the frequency of circulating influenza-specific, interferon gamma-producing memory CD4+ and CD8+ T-cells in healthy children who have received multiple influenza immunizations. METHODS: We evaluated 21 previously immunized children, ages 3 to 9 years, before and 1 month after administration of trivalent inactivated influenza vaccine. Frequencies of influenza-specific CD4+ and CD8+ T-cells stimulated with trivalent inactivated influenza vaccine or A/Panama (H3N2) virus were determined by flow cytometry, and antibody responses to vaccine strains and a drifted H3N2 strain were measured by hemagglutination inhibition assay and neutralizing antibody assays. RESULTS: Mean change in CD4+ and in CD8+ T-cell frequencies after immunization was 0.01% (P > 0.39) with postimmunization CD4+ frequencies higher than CD8+ frequencies. Children with more previous vaccinations had a higher baseline frequency of CD4+ T-cells (P = 0.0002) but a smaller increase or even a decline from baseline after immunization (P = 0.003). An association between age and change in frequency was not detected. Baseline geometric mean titers (GMTs) and seroprotection rates were significantly higher in older children against A/Panama (neutralizing baseline GMT, P = 0.0488) and A/New Caledonia (hemagglutination inhibition baseline GMT and seroprotection, P < 0.0297). Baseline GMTs against B/Hong Kong were not associated with age or quantity of prior vaccinations. CONCLUSIONS: These findings suggest that children may plateau in CD4+ T-cell responses to influenza antigens with repeated exposures and that the number of exposures may play a large role in building a memory CD4+ T-cell response to influenza A, perhaps independently from age.     

Recommendations for the Use of Prolonged‐Release Fampridine in Patients with Multiple Sclerosis (MS)

Prolonged‐release fampridine (fampridine PR) is a potassium channel blocker that improves conductivity of signal on demyelinated axons in central nervous system. Fampridine PR has been approved to improve speed of walking in patients with multiple sclerosis. This statement provides a brief summary of data on fampridine PR and recommendations on practical use of the medication in clinical practice, prediction, and evaluation of response to treatment and patient management.     

Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion

BACKGROUND The Pringle maneuver [portal triad obstruction(PTO)] provides huge disturbances during ischemia and even more thereafter in reperfusion.Contrarily, a possible solution may be stable gastric pentadecapeptide BPC 157,with already documented beneficial effects in ischemia/reperfusion conditions.Recently, BPC 157, as a cytoprotective agent, successfully resolved vessel occlusions in rats(ischemic colitis; deep vein thrombosis, superior anterior pancreaticoduodenal vein; bile duct cirrhosis) through rapid collateral vessel recruitment to circumvent vessel occlusion. Thereby, medication BPC 157 regimens were administered as a single challenge before and during ischemia or,alternatively, at various time points during reperfusion.AIM To introduce BPC 157 therapy against pringle maneuver-damage.METHODS In deeply anesthetised rats, the portal triad was clamped up for 30 min. Rats then underwent reperfusion for either 15 min or 24 h. Medication [(10 μg, 10 ng/kg)regimens, administered as a single challenge] picked(a) ischemia, PTO period [at 5 min before(ip) or at 5 or 30 min of ligation time(as a bath to PTO)] or(b)reperfusion, post-PTO period [at 1 or 15 min(bath during surgery) or 24 h(ip)reperfusion-time]. We provided gross, microscopy, malondialdehyde, serum enzymes, electrocardiogram, portal, caval, and aortal pressure, thrombosis and venography assessments.RESULTS BPC 157 counteracts electrocardiogram disturbances(increased P wave amplitude, S1Q3T3QRS pattern and tachycardia). Rapidly presented vascular pathway(portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein) as the adequate shunting immediately affected disturbed haemodynamics. Portal hypertension and severe aortal hypotension during PTO, as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated(during PTO) or completely abrogated(reperfusion); thrombosis in portal vein tributaries and inferior caval vein or hepatic artery was counteracted during portal triad obstruction PTO. Also, counteraction included the whole vicious injurious circle [i.e., lung pathology(severe capillary congestion), liver(dilated central veins and terminal portal venules), intestine(substantial capillary congestion, submucosal oedema, loss of villous architecture), splenomegaly, right heart(picked P wave values)] regularly perpetuated in ischemia and progressed by reperfusion in Pringle rats.CONCLUSION BPC 157 resolves pringle maneuver-damage in rats, both for ischemia and reperfusion.     

Formation of Nanocones on Highly Oriented Pyrolytic Graphite by Oxygen Plasma

Improvement in hemocompatibility of highly oriented pyrolytic graphite (HOPG) by formation of nanostructured surface by oxygen plasma treatment is reported. We have showed that by appropriate fine tuning of plasma and discharge parameters we are able to create nanostructured surface which is densely covered with nanocones. The size of the nanocones strongly depended on treatment time. The optimal results in terms of material hemocompatibility were obtained after treatment with oxygen plasma for 15 s, when both the nanotopography and wettability were the most favorable, since marked reduction in adhesion and activation of platelets was observed on this surface. At prolonged treatment times, the rich surface topography was lost and thus also its antithrombogenic properties. Chemical composition of the surface was always more or less the same, regardless of its morphology and height of the nanocones. Namely, on all plasma treated samples, only a few atomic percent of oxygen was found, meaning that plasma caused mostly etching, leading to changes in the surface morphology. This indicates that the main preventing mechanism against platelets adhesion was the right surface morphology.     

Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system

We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 microg/kg, 10 ng/kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N(G)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-alpha-methylprednisolone (1 mg/kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro/microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.     

Light chain deposition disease restricted to the brain: The first case report

A 35-year-old white male with symptoms of paranoid schizophrenia was treated by psychiatrists for 13 years. During the final year, he developed severe dysphagia, reduced strength of the upper extremity muscles, and cognitive dysfunction. The patient died in his sleep. The only pathology found in coronal brain sections was ill-defined periventricular foci with prominent, firm vessels. Microscopy revealed abundant, hematoxylin and eosin-eosinophilic, periodic acid-Schiff-positive, thioflavin T-positive, and Congo red-negative deposits in the vessel walls, with hypoxic encephalopathy in the affected regions. Immunohistochemistry showed lambda light chains as the main component of the deposits. Ultrastructural analysis showed amorphous electron dense material in the vessel walls. Perivascular B-cell proliferation was present in the vicinity of affected areas. Polymerase chain reaction was applied for the assessment of B-cell clonality, revealing monoclonal rearrangement of the heavy chain Ig gene. Neither in the kidney nor in any other organ were deposits detected. This is the first case report of light chain deposition disease restricted to the brain.     

Severely hypoplastic amelogenesis imperfecta with taurodontism

BACKGROUND: The prominent dental feature of a boy was severely hypoplastic enamel in both primary and permanent teeth. CASE REPORT: Many permanent teeth were already infected while emerging in the oral cavity. Panoramic radiograph showed enlarged and elongated pulp chambers (taurodontism) in the permanent first molars. The clinical and radiological diagnosis was either hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (AIHHT) or tricho-dento-osseous syndrome (TDO). Histological examination of the upper right permanent first molar revealed thin lamellar or somewhat thicker amorphous enamel on approximal surface only with no rods or incremental lines visible. Histologically, the Witkop type AIG designated 'enamel agenesis' cannot be excluded. The medical and dental history of the family members, as well as the boy's medical examination, was noncontributing. He had thick, blond, curly hair. The bone structure of the jaws and skull was normal. For genetic analysis, DLX3 gene was sequenced but no mutation was found. CONCLUSIONS: Since the gene defect of TDO has been localized only in the DLX3 gene, the more probable diagnosis was AI.     

Phenotype and enamel ultrastructure characteristics in patients with ENAM gene mutations g.13185-13186insAG and 8344delG

OBJECTIVE: The main clinical manifestations of amelogenesis imperfecta (AI) include alteration in the quality and quantity of enamel. AI is associated with different mutations in four genes: enamelin (ENAM), amelogenin (AMGX), kallikrein (KLK4) and enamelysin (MMP-20). Seven different mutations have been identified in the enamelin gene (ENAM). DESIGN: In this paper, we describe the phenotype and ultrastructure of enamel observed using scanning electron microscopy (SEM) in patients with two autosomal dominant (AD) mutations in the ENAM gene: g.13185-13186insAG and g.8344delG, each in one of two unrelated families. Mutations were confirmed by sequence analysis of PCR amplified products of all 10 exons and exon/intron boundaries of the ENAM gene. RESULTS: Phenotypic diversity was observed in patients with ENAM gene mutations g.13185-13186insAG with consecutive protein alteration designated as p.P422fsX488 within family 1. In the proband, the enamel of his entire dentition was chalky white with only mild local hypoplastic alteration, while the phenotypic appearance of his father's dentition was that of local hypoplastic AI. In patients with the ENAM gene mutation g.8344delG from family 2 with consecutive protein alteration designated as p.N197fsX277, generalised hypoplastic AI was observed. CONCLUSIONS: Ultrastructural enamel changes in the patient with the autosomal dominant ENAM g.13185-13186insAG mutation, described for the first time in this study, were less pronounced compared to ultrastructural changes in patients with the autosomal dominant ENAM mutation 8344delG. Ultrastructural characteristics of the g.13185-13186insAG mutation revealed deformed prisms, an oval shape on the cross-section and wider interprism spaces, while enamel with the ENAM mutation 8344delG was laminated, but prismless.     

Glycine-amide is an active metabolite of the antiretroviral tripeptide glycyl-prolyl-glycine-amide

The chemically modified tripeptide glycyl-prolyl-glycine-amide (GPG-NH(2)) inhibits replication of human immunodeficiency virus (HIV) type 1 (HIV-1) in vitro, probably by interfering with capsid formation. The aim of the present study was to determine whether the metabolites glycyl-proline (GP-OH), glycine (G-OH), prolyl-glycine-amide (PG-NH(2)), proline (P-OH), and glycine-amide (G-NH(2)) from proteolytic cleavage may inhibit the replication of HIV-1 in vitro. PG-NH(2) has previously been shown to have a modest effect on HIV-1 replication. In the present study we show that G-NH(2) exhibits a pronounced inhibitory effect on HIV-1. This effect was not due to a decrease in cell proliferation or viability and could not be shown for herpes simplex virus type 1. The G-NH(2) concentration that inhibited virus replication by 50% (IC(50)) was equimolar to that of GPG-NH(2) and ranged from 3 to 41 microM. Transmission electron microscopy revealed that the effect of G-NH(2) on HIV-1 morphology was equivalent to that of GPG-NH(2) and showed disarranged capsid structures, indicating interference with capsid formation. Serial passage of HIV-infected cells with G-NH(2) for more than 20 subcultivations did not decrease the susceptibility to the compound. The results from this study suggest that GPG-NH(2) might act as a prodrug and that G-NH(2) is an active antiretroviral metabolite.