Search PubMed⌕ Search

Biomedical subjects

M Zaremba

Publications and source records attributed to M Zaremba.

At least 19 recordsLinked to original sources

Concomitant up-regulation of astroglial high and low affinity nerve growth factor receptors in the CA1 hippocampal area following global transient cerebral ischemia in rat.

We have examined the effect of global transient cerebral ischemia, evoked in rat by 10 min of cardiac arrest, upon the changes in the cellular expression of two nerve growth factor (NGF) receptors (TrkA and p75) in the hippocampus. We have used immunocytochemical procedures, including a quantitative analysis of staining, along with some quantitative morphological analyses. We have found, under ischemic conditions, a decrease of TrkA immunoreactivity in degenerating CA1 pyramidal neurons and in neuropil. On the other hand, a strong, ischemia-induced up-regulation of TrkA and p75 immunoreactivity was observed in the majority of reactive astroglia population in the adjacent CA1 hippocampal region. The colocalization of the two receptors in the same reactive astroglial cells was evidenced by double immunostaining and further supported by quantitative morphological analysis of TrkA and p75 immunoreactive glial cells. Our data implicate the involvement of NGF receptors in the postischemic regulation of astrocytic function; however, the lack of NGF receptor expression on some astrocytes suggests heterogeneity of astroglia population. Our results also indicate that the lack of neuroprotective action of astroglial NGF induced in the ischemic hippocampus [J Neurosci Res 41 (1995) 684; Acta Neurobiol Exp 57 (1997) 31; Neuroscience 91 (1999) 1027] is not caused by a paucity of NGF receptors but may rather be due to the counteraction of some proinflammatory substances, released simultaneously by glia cells. On the other hand, the up-regulated astroglial TrkA receptor may be an important target for exogenous NGF, which, as previously described [J Neurosci 11 (1991) 2914; Neurosci Lett 141 (1992) 161], exerts a neuroprotective effect in ischemia.

Animals↗

High-affinity NGF receptor in the rat spinal cord during acute and chronic phases of experimental autoimmune encephalomyelitis: a possible functional significance.

The biological effects of Nerve Growth Factor (NGF) are primarily mediated via its high affinity receptor-TrkA. In the present study, we examined the effect of experimental autoimmune encephalomyelitis (EAE) upon the expression of TrkA in neuronal and non-neuronal cells of the spinal cord of Lewis rats during the acute (14 days postimmunization) and chronic (12 months postimmunization) phases of the disease. In the normal spinal cord, both of mature and aged rats, we found TrkA immunoreaction (TrkA-IR) in the motoneurons of the Rexed lamina IX and in both oligo- and astroglia cells. In the acute phase of the disease, we found a reduction of TrkA immunoreactivity in motoneurons and its up-regulation in oligodendroglia, mainly in the white matter. We also confirmed our previous findings concerning the up-regulation of TrkA-IR in astroglia. Both neuronal and non-neuronal changes of TrkA immunoreactivity had a transient character: they were not seen in the chronic phase of the disease. Our results suggest that both neuronal and glial TrkA expression changes depend on inflammation. Moreover, our data indicate that, during the acute phase of EAE, the glial cells become more receptive to NGF, pointing to glia as an important target for pharmacological manipulations, particularly for exogenously administered NGF.

Acute Disease↗

Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure.

We investigated the effect of trimethyltin (TMT), a well-known neurotoxicant, on murine hippocampal neurons and glial cells. Three days following intraperitoneal (i.p.) injection of TMT into 1-month-old Balb/c mice at a dose of 2.5 mg/kg body weight we detected damage of the dentate gyrus granular neurons. The dying cells displayed chromatin condensation and internucleosomal DNA fragmentation, which are the most characteristic features of apoptosis. To study, if prolyl oligopeptidase is engaged in neuronal apoptosis following TMT administration, we pretreated mice with the specific inhibitor--Fmoc-Pro-ProCN in doses of 5 and 10 mg/kg body weight (i.p. injection). Three days following injection we did not observe any attenuation of neurotoxic damage, regardless of inhibitor dose, indicating the lack of prolyl oligopeptidase contribution to neuronal injury caused by TMT. The neurodegeneration was associated with reactive astrogliosis in whole hippocampus, but particularly in injured dentate gyrus. The reactive astrocytes showed an increased nerve growth factor (NGF) expression in ventral as well as dorsal hippocampal parts. NGF immunoreactivity was also augmented in neurons of CA3/CA4 areas, which were almost totally spared after TMT intoxication. It suggested a role for this neurotrophin in protection of pyramidal cells from loss of connection between CA3/CA4 and dentate gyrus fields. The granule neurons' death was accompanied by increased histochemical staining with isolectin B4, a marker of microglia, in the region of neurodegeneration. The microglial cells displayed ramified and ameboid morphology, characteristic of their reactive forms. Activated microglia were the main source of interleukin 1beta (IL-1beta). It is possible that this cytokine may participate in neurodegeneration of granule cells. Alternatively, IL-1beta elaborated by microglia could play a role in increasing NGF expression, both in astroglia and in CA3/CA4 neurons.

Animals↗

The upregulation of nerve growth factor receptors in reactive astrocytes of rat spinal cord during experimental autoimmune encephalomyelitis.

Using immunocytochemistry, we have examined the effect of experimental autoimmune encephalomyelitis (EAE) upon the expression of nerve growth factor (NGF) and its TrkA and p75 receptors in astroglia cells of the spinal cord of Lewis rats. We have found that, in normal spinal cord, astroglia of white matter expressed both NGF receptors while those in gray matter expressed only TrkA and no astroglia expressed NGF. During EAE, strong upregulation of TrkA in the astroglia of gray and white matter was found, particularly in a population of radially oriented astrocytes. An upregulation of p75 was noted in radial astroglia and, to some extent, also in the stellate astrocytes of white matter. In general, the upregulation of NGF receptor immunoreactivities in astroglia correlated with the strong intensification of glial fibrillary acidic protein immunocytochemistry, a prominent feature of EAE. No NGF immunoreactivity appeared in any astroglia cells during EAE. Our results suggest that, during EAE, astroglia of the spinal cord become particularly receptive to NGF, possibly as part of a mechanism enabling astroglial cells to respond to localized release of neurotrophins. Moreover, our data suggest that spinal cord astroglia cells may be a potential target for pharmacological manipulations in EAE.

Animals↗

Interleukin 6, tumor necrosis factor alpha and their soluble receptors in the blood serum of patients with denture stomatitis and fungal infection.

Determinations of the blood serum levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and their soluble receptors (sIL-6R, sTNFR) in denture stomatitis patients (DS) were performed. Serum levels of interleukins and their soluble receptors were measured using the ELISA method. In all examined patients mycological diagnostics were conducted using API 20C AUX stripe tests and an automatic ATB machine. Results were compared with those of healthy denture wearers (D), and controls (C). In DS patients, yeasts were isolated in 90.9%, in D in 66.7% of cases. The most often isolated species in both groups was Candida albicans. Mean concentrations of IL-6 and TNF-alpha were statistically significantly higher in DS and D groups compared to controls. Mean concentrations of sIL-6R were similar in all groups; however, concentrations of sTNFR in both DS and D groups were significantly lower compared to controls. There were no correlations found between values of IL-6 and TNF-alpha nor between examined interleukins and their soluble receptors.

Adult↗

Prolonged and concomitant induction of astroglial immunoreactivity of interleukin-1beta and interleukin-6 in the rat hippocampus after transient global ischemia.

We have investigated the pattern of expression of IL-1beta and IL-6 immunoreactivities in rat hippocampus after transient complete brain ischemia evoked by a 10 min cardiac arrest, at survival times ranging from 1 day to 28 days. To identify the cell types expressing the two immunoreactivities we used specific cell markers and combined staining procedures. In the intact brain IL-1beta and IL-6 were mainly localized in neurons particularly in pyramidal and granular cell layers. Ischemic insult resulted in a concomitant induction of IL-1beta and IL-6 immunoreactivities in multiple astroglia especially in the CA1 area which is the most vulnerable to ischemic insult as manifested by a massive delayed neuronal death accompanied by an intense gliosis. The number of astroglia expressing both immunoreactivities and the intensity of staining was maximal at the 14th day and remained at the same level at the 28th day. Our data suggest that the astroglial IL-1beta and IL-6 may affect the neurodegeneration of CA1 neurons in the ischemic hippocampus and that the prolonged proinflammatory effects of IL-1beta prevail over the presumed protective action of IL-6.

Animals↗

GM1 ganglioside potentiates trimethyltin-induced expression of interleukin-1 beta and the nerve growth factor in reactive astrocytes in the rat hippocampus: an immunocytochemical study.

This study demonstrates potentiation by GM1 ganglioside treatment of trimethyltin (TMT) induced reactivity of astrocytes, and the expression of astroglial interleukin-1 beta (IL-1 beta) and nerve growth factor (NGF) immunoreactivities in the rat hippocampus. GM1 treatment also results in an increase of the number of IL-1 beta and NGF immunoreactive astrocytes. Both the intensity of gliosis and stimulation of IL-1 beta and NGF expression in astrocytes mostly occurs in the regions of heaviest neurodegeneration in the hippocampus (CA4/CA3c and CA1). It is tempting to assume that enhancement of astroglial NGF expression by GM1 ganglioside may play a role in the protective action of GM1 against neurotoxic insult.

Animals↗

A study of the pharmacokinetics and tissue residues of an oral trimethoprim/sulphadiazine formulation in healthy pigs.

Twenty-six healthy female pigs weighing 19.5-33 kg were used in three separate experiments. The animals were fed individually twice a day. Trimethoprim/sulphadiazine (TMP/SDZ) formulation was added to feed in the amount of 6 mg/kg bw (TMP) and 30 mg/kg bw (SDZ). TMP and SDZ concentrations in blood plasma, muscles, liver and kidneys were measured. Pharmacokinetic parameters show that the absorption of TMP from the alimentary tract in pigs is faster than the absorption of SDZ, and the elimination of TMP is slower than that of SDZ. The absorption half-lives were 0.96 (TMP) and 2.24 h (SDZ), whereas elimination half-lives were 5.49 (TMP) and 4.19 h (SDZ). The observed TMP:SDZ ratios in blood plasma after multiple dose administration ranged from 1:11.4 to 1:23.2. One day after administration of the last dose of TMP/SDZ the plasma concentration ratio was 1:15.5, but in muscles, liver and kidneys it was much lower: 1:0.79, 1:0.14 and 1:1.53 respectively. The absolute TMP and SDZ tissue concentrations 1 day after the last multiple dose administration were very low (maximum TMP: 0.29 micrograms/g in liver; maximum SDZ: 0.23 micrograms/g in kidneys). Neither drug was detected in any tissue 8 days after the last administration of TMP/SDZ. Based on our results, it was concluded that there is no support for the TMP:SDZ pharmaceutical ratio 1:5 in oral formulations of these compounds for pigs. The administration oral TMP/SDZ formulations once a day may result in the absolute tissue concentrations of these drugs being too low for antibacterial activity. The withdrawal period for such an oral TMP/SDZ formulation for pigs (according to accepted guidelines in Europe for MRL of TMP < 0.05 mg/kg of tissue) should not be less than 5 days.

Administration, Oral↗

Trimethyltin-induced plastic neuronal changes in rat hippocampus are accompanied by astrocytic trophic activity.

Partial deafferentation of the hippocampus due to trimethyltin (TMT) intoxication has been reported to induce plastic rearrangements of neuronal elements but the factors that direct these responses are unknown. To assess the possible involvement of nerve growth factor (NGF) in the phenomenon we evaluated the presumable changes in the expression pattern of NGF immunoreactivity (NGF-IR) in rat hippocampus 21 days after administration of TMT (8 mg/kg, i.p.) when reactive changes are fully developed. Immunolabelling for TrkA known to mediate biological effects of NGF and for GFAP to identify astroglial cells as a one of presumed source of postinjury produced factors was carried out on adjacent sections to establish the relation between expression of these proteins. In control hippocampus NGF-IR and TrkA-IR were localized in neurons and/or neuropil. After exposure to TMT remarkable non-neuronal expression of both proteins was observed. The distribution pattern of NGF, TrkA and GFAP overlapped suggesting that reactive astrocytes may not only produce NGF but also may become responsive to this neurotrophin. Zones of extensive NGF and TrkA astroglial expression corresponded to areas of axonal-dendritic rearrangements reported earlier. The data suggest that astroglia-derived trophic activity may be involved in neuronal plastic events associated with treatment with TMT.

Animals↗

Axonal accumulation of p75NTR and TrkA in the septum following lesion of septo-hippocampal pathways.

Septal cholinergic neurones depend on trophic support by nerve growth factor (NGF) which can rescue them from injury-induced degeneration. Since NGF exerts its effects via p75NTR and TrkA receptors coexpressed in vast majority of these neurones and down-regulated without NGF treatment after injury, in this study we aimed to examine how does the lesion to the cholinergic tracts affect distribution of both types of receptor proteins in damaged fibres. Early changes (two and seven days) were examined immunocytochemically within the septum and supracallosal stria after unilateral lesion to the supracallosal area and cingulum transecting some septal cholinergic efferents. We found accumulation of p75NTR and TrkA immunoreactive material (so-called "pile-up") within axonal segments of distended appearance proximal to the transection at two days postlesion and its translocation towards cell bodies seven days postsurgery. We observed p75NTR pile-up to be more intense than TrkA, which may indicate different cellular concentrations of both receptors. Receptor pile-up resembled acetylcholinesterase pile-up reported previously, suggesting a common response mechanism involving axonal transport disturbances.

Acetylcholinesterase↗

Difluoromethylornithine counteracts lesion-induced astrogliosis in rat hippocampus: enhancement of inhibitory effect by combined treatment with GM1 ganglioside.

The effect of difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the rate limiting enzyme of polyamine biosynthesis, and its combined action with GM1 ganglioside, was studied on the GFAP content in a model of remote astrogliosis evoked in the hippocampus by lateral fimbria transection. DFMO markedly suppressed hippocampal gliosis as measured by GFAP immunoblotting seven days postsurgery. Combined treatment with DFMO and GM1 ganglioside--a substance which alone also counteracts hippocampal gliosis, produced a stronger suppressive effect than DFMO. The results support the hypothesis of a causal link between lesion induced events: polyamine biosynthesis and astroglial reaction. Potentiation of the inhibitory effect of DFMO by GM1 ganglioside suggests that the latter does not act through the mechanism involving ODC suppression.

Animals↗

Bilateral gliosis in unilaterally lesioned septohippocampal system: changes in GFAP immunoreactivity and content.

Unilateral damage to the lateral fimbria led to a bilateral gliosis in the septum and hippocampus. The gliosis was manifested by an increase in GFAP staining, accompanied by an increased number of glial fibrillary acidic protein (GFAP)(+) cells and GFAP content; the latter however was not visible in the contralateral septum. In general, the contralateral reaction appeared weaker than the ipsilateral one. The pattern of contralateral increase in GFAP-immunoreactivity (IR) matched almost exactly that observed on the ipsilateral side in the hippocampus (the most evident increase was seen in the oriens and pyramidal layers of cornu Ammonis 3 and in polymorphic area of gyrus dentatus). In the septum the bilateral increase in GFAP-IR was mainly visible in the dorsolateral quadrant of the structure; however in the ipsilateral side it spread over the whole half of the structure. The astrocytic responses in the septum and hippocampus were not equivalent: they differed mainly with regard to the increase of GFAP(+) cells (over 300% of control in the anterior part of the septum and only about 120% in the dorsal hippocampus). The differences between the percentage increases of other gliotic indices: GFAP-IR and GFAP content. Various possibilities that may account for the occurrence of contralateral gliosis are discussed, the most plausible being the contribution of interhemispheric and intraseptal links and the action of some diffusible agents. We suggest that bilateral gliosis may have an impact on compensatory postlesion processes, possibly by providing trophic support to impaired neurons.

Animals↗

[Diagnostic value of the latex test (Pyloriset) for detection of Helicobacter pylori antibodies in adult patients with upper digestive tract diseases].

The biopsy specimens and sera from 269 adult patients referred for gastroscopy were examined for Helicobacter pylori infections. The bacteriologic studies included: Gram smears, urease test and culture methods of biopsy specimens, biochemical tests for identification of isolates and their sensitivity testing to 17 chemotherapeutics. The biopsy specimens were examined histopathologically also. For demonstration of specific antibodies the latex test (Pyloriset, Orion Diagnostica, Finland) was used. Biopsy--cultures were positive for H. pylori in 171 (63.6%) cases, biopsy--urease test in 149 (55.4%) and Gram smears in 163 (62.8%). A total of 193 (71.7%) positive sera with latex were found. The sensitivity and specificity of the latex test as compared with the culture method, biopsy--urease test and Gram smears was 80.7% and 43.9%, 80.5% and 39.2% or 79.8% and 40.6% respectively. All three direct diagnostic methods were positive in 122 (45.4%) patients, 101 (82.8%) of them were positive with the latex test. Only in 33 (19.3%) patients with positive biopsy--culture for H. pylori anti-H. pylori antibodies were not observed. On the other hand, among 75 patients with negative all direct methods for H. pylori infections 39 (52.0%) of them were positive with the latex test. The latex test was also positive in 56 (54.9%) sera among 102 blood donor tested by us but this value was lower, in trems of statistical significance than in patient sera. In conclusion, the latex test may be useful as a screening serological test for the diagnosis of patients with H. pylori infections and for epidemiological studies.

Adult↗

Differential effects of GM1 ganglioside treatment on glial fibrillary acidic protein content in the rat septum and hippocampus after partial interruption of their connections.

The glial fibrillary acidic protein (GFAP) content was investigated using immunoblotting techniques in the septum and hippocampus of the rat after bilateral lateral fimbria transection. Seven days after surgery GFAP content increased significantly both in the septum (140% of control) and hippocampus (120% in dorsal, the less denervated, and 145% in the most denervated ventral part), indicating the occurrence of reactive gliosis. The GM1 treatment caused statistically significant attenuation of GFAP increment in all hippocampal parts. In contrast, GM1 treatment has no influence on the increase of GFAP content in the septum. Results suggest a differential effect of GM1 on the two gliotic reactions formed as a consequence of the lesion at the level of the source of innervation (septum) and the target (hippocampus).

Animals↗

Nerve growth factor induces a dose-dependent and long-lasting increase of choline acetyltransferase activity in the septal area and hippocampus of uninjured rats.

The effect of nerve growth factor (NGF) on the intact septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused at different doses (5-100 micrograms) for two weeks into the lateral ventricle of adult rats. Controls received intracerebroventricular infusion of equal amounts of cytochrome c. Nerve growth factor treatment was capable of inducing a dose-dependent increase of choline acetyltransferase activity (ChAT) in septal area and ventral hippocampus. In both areas, the NGF-induced rise of ChAT activity was sustained for at least one week after infusion, then it progressively declined towards control values. By three and five weeks, using NGF at 25 and 100 micrograms respectively, ChAT increase was still significant in both septum and ventral hippocampus. The present findings corroborate a role for NGF in adult septohippocampal cholinergic system and indicate that the "pharmacological" modulation of these neurons by NGF may last several weeks following withdrawal of this trophic factor.

Animals↗

Nerve growth factor affects uninjured, adult rat septohippocampal cholinergic neurons.

The effect of nerve growth factor on the intact versus injured septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused into the lateral ventricle of adult uninjured rats or rats that had received unilateral partial transection of the fimbria. Controls (operated and unoperated) received intraventricular infusion of cytochrome c. After 2 weeks of nerve growth factor or cytochrome c treatments, choline acetyltransferase and acetylcholinesterase activities were measured in the septal area and in the hippocampus (divided into dorsal, medial and ventral parts). The continuous infusion of nerve growth factor resulted in a marked dose-dependent increase of choline acetyltransferase activity in both septum and hippocampus of adult unlesioned rats. In lesioned rats the nerve growth factor treatment was capable of inducing choline acetyltransferase activity in the hippocampus of not only the lesioned but also the unlesioned side, as well as in the septal area. In addition, nerve growth factor affected choline acetyltransferase activity differently in the hippocampus of the operated side with respect to the contralateral side or in unoperated animals. The chronic infusion of nerve growth factor did not affect acetylcholinesterase activity in the septum or in the hippocampus of either lesioned or unlesioned rats. The present findings indicate that nerve growth factor is capable of modulating the function of not only damaged but also normal adult forebrain cholinergic neurons. This suggests that nerve growth factor may modulate the function of these neurons in adulthood.

Acetylcholinesterase↗

[Usefulness of the diagnostic kit Enteroplast for identification of Enterobacteriaceae].

Comparative evaluation of biochemical properties determined by ENTEROPLAST kit (P.P.Z. Plastomed) and biochemical set of tests (conventional method) of 140 strains representing 12 genera of Enterobacteriaceae family was undertaken. Consistent results positive or negative (in 12 biochemical tests) were obtained in 93%. The highest percentage of inconsistent results of biochemical reactions (positive in conventional method and negative in ENTEROPLAST kit) were observed in following tests: growth on Simmons medium--17.8%, MR--7.8%, fermentation of raffinose--7.2%. Significantly lower percentage of inconsistent results was found in the case of false positive reactions (negative in conventional method and positive in ENTEROPLAST kit). In summary, it seems that Enteroplast kit can be used for routine diagnostic examinations for identification of rods of Enterobacteriaceae family, basing on their biochemical properties.

Bacteriological Techniques↗