Etiology and clinical course of meningitis in children

The aim of the paper was to pinpoint the etiological factors which caused meningitis, and to describe the course of the illness in the patients hospitalized in the years 1991-2000 at the observation ward of the Paediatrics Propaedeutics Clinic of the Paediatrics Institute. Etiological factors were determined in 42 of 80 cases included in the study: in 32 out of 62 purulent meningitis cases and 10 out of 18 aseptic meningitis cases. In purulent meningitis the most commonly isolated pathogens were N. meningitidis (16%), S. pneumoniae (8.1%), K. pneumoniae (4.9%) and H. influenzae type B (4.9%), where as in aseptic meningitis--mumps and herpes viruses. Despite appropriate treatment in 47% of cases there were observed complications such as hydrocephalus, brain oedema, ependymitis as well as hearing or vision impairment and failure to thrive.     

Reconstitution of cyclophosphamide-induced,impaired function of the immune system in animal models

Cyclophosphamide (CY) is an alkylating agent used in chemotherapy of tumors and autoimmune disorders. The drug causes a large number of side-effects including deep, transient lymphopenia and neutropenia, thus rendering the immune system susceptible to infections. In this review we focus on the effects of CY on the haematopoetic system and the immune response in rodents. In addition, we present approaches aimed at reconstitution of lympho- and myelopoiesis using a spectrum of immunotropic factors including: thymic hormones, cytokines, low-molecular weight compounds, bacterial products and lactoferrin.     

Comparison of the content of antioxidant vitamins in the diets of primary school children from Bialystok and its vicinity

A 24-hour history was taken in a group of 169 children aged 9 and 14 years, randomly chosen from two primary schools in Bia?ystok, and 186 children at the same age from three village primary schools. The results were compared to the recommended dietary allowances adequate to age and sex, and subjected to statistical analysis. The mean content of the respective vitamins in the diets of children living in town is higher than their mean content in the diets of village children. In many cases the results are statistically significant. The correction coefficient, allowing estimation of vitamin loss due to food processing was used to analyse the realisation of the vitamin dietary allowances in diet. The realisation of the recommended dietary allowances for the respective vitamins (in %) in the diets of 9- and 14-year old schoolchildren living in suburban areas is considerably lower compared to that noted in town.     

Nociceptin inhibits acquisition of amphetamine-induced place preference and sensitization to stereotypy in rats

Nociceptin (also called orphanin FQ), a 17-amino-acid peptide, is the natural ligand of the nociceptin opioid peptide (NOP) receptor. This peptide shows similarities, in its structure, to opioid peptides, mainly to dynorphin A. However, unlike opioid peptides, it does not produce a conditioned place preference or aversion but inhibits rewarding effect of drugs of abuse. The present study was designed to examine the ability of nociceptin to block the acquisition of amphetamine-induced place preference, and the development of amphetamine-induced sensitization to stereotypy in rats. Our experiments indicated that repeated administration of nociceptin at increasing doses during conditioning significantly attenuated the reinforcing effect of amphetamine in conditioned place preference paradigm. Nociceptin did not change the acute effect of amphetamine-induced stereotypy but prevented the development of sensitization to stereotypy measured on the challenge day. Our results suggest the involvement of nociceptin in long-lasting neuronal adaptation after repeated amphetamine treatment.     

Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors in chick cerebral cortex

In this study receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) were characterized in chick cerebral cortex by an in vitro binding technique, using 125I-labeled VIP ([125I]-VIP) as a ligand. The specific binding of [125I]-VIP to chick cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding sites with high affinity (Kd = 0.21 nM) and low capacity (Bmax = 19.5 fmol/mg protein). The relative rank order of potency of the tested peptides to inhibit [125I]-VIP binding to chick cerebrum was VIP (chicken) > or = VIP (mammalian) > or = PACAP27 > or = PACAP38 > VIP6-28 (mammalian) > PHI (porcine) > neurotensin6-11-chicken VIP7-28 > neurotensin6-11-mammalian VIP7-28 > VIP16-28 (chicken; inactive) approximately secretin (inactive). About 60% of [125I]-VIP-binding sites in chick cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. It has been concluded that the cerebral cortex of chick, in addition to PAC1 receptors, contains a population of VPAC-type receptors.     

Antagonism of VIP-stimulated cyclic AMP formation in chick brain

Of eight peptides tested (0.01-5 microM), only two, that is, pituitary adenylate cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6-27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7-28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute preincubation of chick cortical slices with 5 microM PACAP6-27, NT-cVIP, or NT-mVIP competitively antagonized the cAMP effects of cVIP (0.03-1 microM), with the truncated form of PACAP being the best antagonist. Preincubation of slices with 5 microM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 microM)-induced increase in cAMP production; however its action was independent of the concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic activity against the full-length peptide. In parallel experiments, 30-min pretreatment of cortical slices with 5 microM PACAP6-27 significantly antagonized the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP hybrid was ineffective. It has been concluded that in the chick brain, PACAP and cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively, and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may represent VPACtype receptor-selective blocking activity.     

Switch time-point for rapid experience-dependent changes in zinc-containing circuits in the mouse barrel cortex

It has been previously demonstrated that in the mouse barrel cortex, synaptic zinc is regulated by sensory experience. In adult mice, cutting selected vibrissae produced a rapid but transient elevation of synaptic zinc in the corresponding barrels several hours later, whereas in 8 day-old animals this procedure did not affect synaptic zinc. In the present study, we wished to determine the postnatal age at which zinc-containing terminals gain the ability to respond rapidly to a restriction of sensory input. We therefore examined the effects of 1-day sensory deprivation starting at different postnatal ages. For this purpose we unilaterally trimmed all rows of vibrissae, except for row C, and we then visualized synaptic zinc in the barrel cortex 24h later. Up to postnatal day 15 such procedure had no effect on the level of synaptic zinc. However, beginning at postnatal day 16, 1-day sensory deprivation produced an increase in synaptic zinc within hollows of deprived rows of barrels as compared to non-deprived rows. These results show that during development there is a specific time-point after which zinc-containing circuits may respond rapidly to altered sensory inputs. A comparison of these findings with previous results obtained after chronic sensory deprivation suggests that a specific time window exists in development for persistent alterations in zinc-containing circuits.     

The aptamer ARC1779 blocks von Willebrand factor–dependent platelet function in patients with thrombotic thrombocytopenic purpura ex vivo

BACKGROUND: In thrombotic thrombocytopenic purpura (TTP), ultralarge von Willebrand factor (VWF) multimers bind platelet (PLT) glycoprotein Ib and lead to the formation of disseminated fibrin‐poor, VWF‐rich PLT thrombi. The aptamer ARC1779 blocks binding of the VWF A1 domain to PLT glycoprotein Ib. We evaluated whether ARC1779 inhibits the excessive VWF activity and VWF‐mediated PLT function in patients with TTP. STUDY DESIGN AND METHODS: We studied the ex vivo concentration response curves for ARC1779 on PLT function analyzer (PFA‐100, Dade Behring) and cone‐and‐plate analyzer (CPA, Impact‐R) PLT function tests, agonist‐induced PLT aggregation, and VWF activity of TTP patients (n = 11, three in acute phase and eight in remission) and healthy controls (n = 44). RESULTS: VWF activity and VWF‐dependent PLT plug formation were increased in TTP patients relative to healthy controls, but agonist‐induced PLT aggregation was not. ARC1779 blocked collagen/adenosine 5′‐diphosphate (ADP)‐induced PLT plug formation as measured by PFA‐100 with an inhibitory concentration (IC)₁₀₀ of approximately 1 µg/mL in citrate‐anticoagulated samples and approximately 3 to 4 µg/mL in hirudin‐anticoagulated samples. A similar concentration of ARC1779 was necessary to block shear‐dependent PLT adhesion in both TTP patients and healthy controls using the CPA assay (IC₁₀₀ of approx. 1 µg/mL for both). ARC1779 blocked VWF activity with an IC₉₀ of approximately 3 to 4 µg/mL in all subjects, but did not inhibit PLT aggregation by ADP, collagen, or arachidonic acid even at concentrations much greater than those that fully inhibited VWF‐dependent PLT function. CONCLUSIONS: ARC1779 potently and specifically inhibits VWF activity and VWF‐dependent PLT function. ARC1779 may be a promising novel therapeutic for the treatment of TTP.     

Emergence of Usutu virus,an African mosquito-borne flavivirus of the Japanese encephalitis virus group,central Europe

During late summer 2001 in Austria, a series of deaths in several species of birds occurred, similar to the beginning of the West Nile virus (WNV) epidemic in the United States. We necropsied the dead birds and examined them by various methods; pathologic and immunohistologic investigations suggested a WNV infection. Subsequently, the virus was isolated, identified, partially sequenced, and subjected to phylogenetic analysis. The isolates exhibited 97% identity to Usutu virus (USUV), a mosquito-borne Flavivirus of the Japanese encephalitis virus group; USUV has never previously been observed outside Africa nor associated with fatal disease in animals or humans. If established in central Europe, this virus may have considerable effects on avian populations; whether USUV has the potential to cause severe human disease is unknown.     

Antiproliferative activity of parthenolide against three human cancer cell lines and human umbilical vein endothelial cells

Parthenolide is a major sesquiterpene lactone derived from feverfew (Tanacetum parthenium) with known anti-inflammatory activity. Moreover, the anticancer potential of this compound was suggested. In this study, we determined the effect of parthenolide on proliferation of three human cancer cell lines: human lung carcinoma (A549), human medulloblastoma (TE671), human colon adenocarcinoma (HT-29) and human umbilical vein endothelial cells (HUVEC) in vitro. Cell proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) value (the concentration of drug necessary to induce 50% inhibition) together with confidence limits was calculated. Parthenolide inhibited proliferation of all three types of cancer cells (A549, TE671, HT-29) and HUVEC with the following IC(50) values (in muM): 4.3, 6.5, 7.0 and 2.8, respectively. Thus, the antiproliferative potential of parthenolide was confirmed.