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PubMed2000

Calcified neurocysticercotic lesions and postsurgery seizure control in temporal lobe epilepsy.

BACKGROUND: Several studies suggest that neurocysticercosis is the main cause of symptomatic epilepsy in developing countries. In such areas, calcified cysticercotic lesions (CCL) are frequently found in patients with complex partial seizures associated with hippocampal sclerosis (HS). The authors studied whether there are clinical and pathologic differences between HS patients with and without CCL. METHODS: The authors determined the clinical and pathologic findings of 30 patients with HS and compared them with 32 patients with HS + CCL. Hippocampi from both groups were measured for fascia dentata Timm staining and cell density in hippocampal subfields. RESULTS: In the HS + CCL group, single or multiple CCL were found in all lobes with no lobar predominance. An initial precipitating event occurred in 83.3% of HS and in 62.5% of HS + CCL. First complex partial seizure occurred at 10.1 years in HS and at 11.9 years in HS + CCL. No significant differences were found for fascia dentata Timm staining and hippocampal cell densities. Good postsurgery outcome (Engel I classification) did not differ between groups, with this result occurring in 76.6% of patients with HS and 81.2% of patients with HS + CCL. CONCLUSIONS: The presence of CCL does not influence the clinical and pathologic profile of patients with hippocampal atrophy. Clinical histories and postsurgical outcomes were similar to those of patients with classic HS, suggesting that the CCL is probably, in this set of patients, a coincidental pathology and does not have a role in epileptogenesis.

Adolescent↗
PubMed1984

Heparan sulfate enhances growth of transformed human cells.

Previous studies showed that cell surface heparan sulfate (HS) is involved in density-dependent growth regulation of normal human cells. In this study the effects of HS on proliferation of transformed cells were studied in vitro. Exogenously added HS prepared from normal tissues (rat kidney and bovine kidney) enhanced growth of transformed human and animal cells (gamma ray- or virus-transformed WI-38, and HeLa cells and chemically induced mouse hepatoma cells), but inhibited that of normal human and animal cells (WI-38, 3T3, and rabbit liver cells). HS was less effective on growth of both normal and transformed human cells at higher cell density. Although the exogenous HS did not bind to cells tightly, HS was found to affect cell growth not by modulation of growth-related substances in the medium, but through contact with the cell surface. HS preparation from tumour cells (mouse hepatoma cells) exerted similar effects on cell growth. Heparin, structurally similar to HS, inhibited growth of both normal and transformed human cells. These findings suggest that: 1. HS plays a particular function in contact regulation of cell proliferation. 2. Transformation-related changes in the structure of HS molecules do not much affect the function of HS. 3. The cellular transformation, however, is accompanied by alteration in the growth-regulating system sensitive to extracellular HS.

Animals↗
PubMed2002

Regulation of heat shock proteins, Hsp70 and Hsp64, in heat-shocked Malpighian tubules of Drosophila melanogaster larvae.

It is known from earlier studies that the heat shock (HS) response in Malpighian tubules (MTs) of Drosophila larvae is different from that in other tissues because instead of the Hsp70 and other common heat shock proteins, Hsp64 and certain other new proteins are induced immediately after HS. In the present study, we examined the kinetics of the synthesis of Hsp70 and Hsp64 immediately after HS and during recovery from HS by 35S-methionine labeling and Western blotting. In addition, we also examined the transcriptional activity of hsp70 genes in larval MT cells at different times after HS by in situ hybridization and Northern blotting. The HS-induced synthesis of Hsp64 ceased by 1 hour of recovery from the HS when synthesis of the Hsp70 commenced. Our results revealed that the induced synthesis of Hsp64 immediately after HS was dependent on new transcription. Although the levels of Hsp70 in MT cells rapidly increased after its synthesis began during recovery, the levels of Hsp64 remained unaltered irrespective of its new synthesis occurring during or after HS. Inhibition of new Hsp64 synthesis by transcriptional or translational inhibitors also did not affect the total amount of this protein in MTs. The Hsp64 polypeptides synthesized in response to HS are degraded rapidly. Apparently, the cells in MTs maintain a balance between new synthesis of Hsp64 and its turnover so that under all conditions a more or less constant level of this protein is maintained. Although the Hsp70 synthesis started only after 1 hour of recovery, the hsp70 genes were transcriptionally activated immediately after HS and they continued to transcribe till at least 4 hours after the HS. The hsp70 transcripts in MT cells that recovered for 2 hours or longer did not contain the 3' untranslated regions (UTRs), which may allow their longer stability and translatability at normal temperature. Synthesis of Hsp70 during recovery period was dependent on continuing transcription. Assessment of the beta-galactosidase activity in 2 transgenic lines carrying the LacZ reporter gene under hsp70 promoter and different lengths of the 5'UTR suggested that the delayed translation of hsp70 transcripts in MTs is probably regulated by some elements in the 5'UTR.

3' Untranslated Regions↗
PubMed2001

Evaluation of disuse atrophy of rat skeletal muscle based on muscle energy metabolism assessed by 31P-MRS.

The purpose of this study was to evaluate disuse atrophy of skeletal muscle using a hind-limb suspension model, with special reference to energy metabolism. Twenty-four Sprague-Dawley rats were divided into four groups: control group (C), hind-limb suspended for 3 days (HS-3), for 7 days (HS-7) and for 14 days (HS-14). The gastrocnemius-plantaris-soleus (GPS) muscles in each group were subjected to the following measurements. After a 2-min rest, contraction of the GPS muscles was induced by electrical stimulation of the sciatic nerve at 0.25 Hz for 10 min, then the frequency was increased to 0.5 and 1.0 Hz every 10 min. During the stimulation, twitch forces were recorded by a strain gauge, and 31P-MRS was performed simultaneously. Maximum tension was measured at the muscle contraction induced at 0.25 Hz; the wet weight of the whole and each muscle in the GPS muscles was also measured. From the 31P-MR spectra during muscle contraction, the oxidative capacity was calculated and compared among the groups. The weights of the whole GPS muscles in C, HS-3, HS-7 and HS-14, were 2.66 +/- 0.09, 2.39 +/- 0.21, 2.34 +/- 0.21 and 2.18 +/- 0.14 (g) respectively. Thus, the muscle mass significantly decreased with time (p < 0.05). Among the GPS muscles, the decrease in weight of the soleus muscle was especially remarkable; in the HS-14 group its weight decreased to 60% of that in the C group. We evaluated maximum tension and oxidative capacity as the muscle function. The maximum tensions in C, HS-3, HS-7 and HS-14 were 519 +/- 43, 446 +/- 66, 450 +/- 23 and 465 +/- 29 (g), respectively. This was significantly greater in the C group than in any other groups, however there were no significant differences among the three HS groups. The oxidative capacity during muscle contraction in the C group was higher than in any HS group and it did not further decrease even if the suspension of the limbs was prolonged beyond 3 days. The present study showed that in disuse atrophy, muscle mass and muscle function did not change simultaneously. Thus, it is necessary to develop countermeasures to prevent muscle atrophy and muscle function deterioration independently.

Animals↗
PubMed2005

The effects of halothane sensitivity on carcass composition and meat quality in HAL-1843-normal pigs.

Objectives of this study were to determine the incidence of halothane sensitivity in pigs that are homozygous normal at the ryanodine receptor nucleotide 1843 (HAL-1843-normal) and the relationships between halothane sensitivity and carcass composition or meat quality. In Exp. 1, piglets (Lines A, B, C, and D; n = 168, 170, 168, and 169, respectively) were obtained from mating a HAL-1843-normal sire line to four HAL-1843-normal dam lines. In Exp. 2, piglets from Lines A and B (n = 87 and 90, respectively) were included with piglets (Lines E, F, G, and H; n = 94, 92, 89, and 89, respectively) obtained from mating four HAL-1843-normal sire lines to a single HAL-1843-normal dam line. Pigs were subjected to 3% halothane at approximately 9 wk of age. In Exp. 1, limb rigidity, blotching of the skin, and muscle tremors were visually assessed, and based on these criteria, halothane sensitivity (HS) was observed in 48% of the pigs. To better characterize this response, a scoring system was developed and used in Exp. 2. Using this system, 25, 42, and 33% of the pigs in E and 40, 33, and 27% of the pigs in Line G were categorized as HS-low (HS-L), HS-intermediate (HS-I), and HS-high (HS-H), respectively. In Lines F and H, 13 and 18% of the pigs were HS-I, and 0 and 2% were HS-H, respectively. No consistent effects due to HS were observed in carcass composition or meat quality; however, when a subset of pigs from Exp. 2 were subjected to more extensive handling and transportation before slaughter, ultimate pH was lower and drip loss was higher in LM from HS-H compared with HS-L pigs (P < 0.05; n = 71). These results demonstrate that some pigs are sensitive to halothane anesthesia even in the absence of the known HAL-1843 polymorphism. Additionally, halothane sensitivity may be associated with inferior pork quality under adverse antemortem conditions.

Anesthetics, Inhalation↗
PubMed1996

Regulation of gene expression and activity of malic enzyme in liver of hereditary hypertriglyceridemic (hHTG) insulin resistant rat: effect of dietary sucrose and marine fish oil.

The effect of increased dietary intake of n-3 polyunsaturated fatty acids (PUFA) on hepatic malic enzyme (EC 1.1.1.40) gene expression and activity was investigated in either hereditary fixed or dietary induced hypertriglyceridemia after euglycemic hyperinsulinemic (6.4 mU/kg/min) clamp. The hereditary hypertriglyceridemic rats (hHTG) were fed for 2 weeks basal (B) or high (63 cal %) sucrose (HS) diet, with or without fish oil (FO, 30 wt % n-3 PUFA). The results were compared with the data obtained in control (C) animals subjected to identical protocol. In hHTG rats, increased gene expression [hHTG: 1.7 +/- 0.1 vs. C: 0.5 +/- 0.05 arbitrary units (AU), P<0.02] for malic enzyme (ME) was not accompanied by increased activity of this enzyme in liver [hHTG: 1.1 +/- 0.1 vs. C: 3.1 +/- 0.4 nkat/mg, P<0.001]. HS feeding raised the activity [HS-hHTG: 4.2 +/- 0.3 nkat/mg, P<0.001; HS-C: 7.5 +/- 0.9 nkat/mg, P<0.001] and mRNA levels [HS-hHTG: 10.4 +/- 0.3 AU, P<0.001; HS-C: 7.7 +/- 0.3 AU, P<0.001] in liver of both hHTG and control rats. The supplementation of HS diet with FO led to striking suppression of activity by 63 % [2.8 +/- 0.5 nkat/mg, P<0.001] and gene expression [2.9 +/- 0.2 AU, P<0.001] for ME in liver of control rats. Such inhibitory effect was not as pronounced in hHTG rats and reached about 50 % in the ME activity [HS+FO: 2.0 +/- 0.06 nkat/mg vs. HS:4.2 +/- 0.3 nkat/mg, P<0.001] or 30 % decrease in ME mRNA levels [HS+FO: 7.5 +/- 0.8 Au vs. HS:10.4 +/- 0.3 AU, P<0.001]. Thus, hHTG rats have markedly elevated levels of mRNA for malic enzyme in liver accompanied by decreased enzymatic activity. Dietary manipulations leading to alteration of hypertriglyceridemia (HS diet, omega-3 PUFA) influenced both the activity of malic enzyme and its transcription in the liver.

Journal Article↗
PubMed2004

Increased salt sensitivity induced by sensory denervation: role of superoxide.

AIM: To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and contributes to the development of hypertension induced by sensory denervation plus high salt intake. METHODS: Newborn Wistar rats were given capsaicin 50 mg/kg sc on the 1st and 2nd d of life. After weaning, male rats were grouped as follows and treated for 3 weeks with: capsaicin pretreatment plus normal sodium diet (0.5 %, CAP-NS), CAP plus high sodium diet (4 %, CAP-HS), control plus NS (CON-NS), or CON-HS. Both tail-cuff systolic blood pressure and mean arterial pressure (MAP) were measured in each of the groups. Western blot analysis was used for measurement of manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) in the mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for superoxide production in the mesenteric resistance arteries. The Griess method was used for measurement of nitrite/nitrate levels in plasma. RESULTS: Both tail-cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CON-NS rats (P<0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, nitrite/nitrate levels in plasma were not different among 4 groups. Acute iv administration of tempol, a membrane-permeable superoxide scavenger, decreased MAP in both CAP-HS and CON-HS when compared with their respective controls. However, the decreases of MAP between these two groups were not different. Chronic treatment with tempol failed to prevent the development of hypertension in CAP-HS rats. Superoxide production in the mesenteric resistance arteries was increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, chronic treatment with tempol did not prevent the increase of mesenteric superoxide production in CAP-HS rats. CONCLUSIONS: Regardless of increased vascular MnSOD levels, salt sensitive hypertension induced by sensory degeneration is associated with increased vascular superoxide production. Although tempol is incapable of preventing the development of hypertension in sensory denervated rats fed a high salt diet, increased superoxide levels may contribute to exacerbated vascular impairment which may take longer time to develop. Given that superoxide may be produced by sources other than mitochondrion, future studies using other inhibitors (eg, inhibitors of NADPH oxidase and xanthine oxidase) may unveil the effectiveness of reducing superoxide on lowering blood pressure in this model.

Animals↗
PubMed1990

[Hyperosmolar volume replacement in heart surgery].

The ideal solution for use in volume therapy is still a matter of debate. Hypertonic sodium (HS) solutions have been advocated for resuscitation from hemorrhagic shock (small volume resuscitation). As hypertonic fluids may also be of interest in cardiac surgery, the effects of a new HS solution were studied. METHODS. In 90 patients undergoing aorto-coronary bypass grafting studies were performed at three different periods: I (n = 30) after induction of anesthesia (before onset of the operation); II (n = 30) during cardiopulmonary bypass (CPB); III (n = 30) after termination of bypass. During these periods the patients were randomly allocated to one of three groups with 10 patients in each group: group 1 received a new hypertonic solution prepared in hydroxyethyl starch (HES) solution (72 g/l NaCl, 60 g/l HES, 2400 mosmol/l; HS-HES patients), group 2 received a 6% HES solution (200/0.5; HES patients), and group 3 received no volume infusion and served as controls. RESULTS. After the induction of anesthesia, significantly less HS-HES solution (4.5 +/- 0.5 ml/kg) than 6% HES solution (10.1 +/- 1.4 ml/kg) was necessary to double the baseline PCWP. The fluid balance during CPB was negative in the patients who had received HS-HES preoperatively (-0.03 +/- 0.01 ml/kg.min CPB), whereas 6% HES (+0.06 +/- 0.02 ml/kg.min CPB) and control patients (+0.13 +/- 0.03 ml/kg.min CPB) had a positive fluid balance. Both after the induction of anesthesia and after termination of bypass, CI increased more in the HS-HES group than in the HES patients, and it even decreased in the control group. SVR decreased in the HS-HES patients, whereas it increased in the control group. Rapid infusion of HS-HES during CPB was followed by a significant, but short-lasting decrease in MAP (-40 mmHg) and an increase in the oxygenator volume. Pulmonary gas exchange (= paO2) was least compromised in the HS-HES patients; the sodium concentration increased only in the HS-HES patients, but never exceeded 150 mmol/l. DISCUSSION. Cardiac surgery procedures offer a special situation for volume therapy as there is a possibility of deterioration in the macro- and microcirculation before, after, and during the period of CPB. Hemodynamic effects of the new HS-HES solution included an increase in CI and a decrease in SVR, which were not merely transient as has been reported which hypertonic saline solution used alone. It was also observed that HS-HES patients required significantly smaller volumes of fluids, both during CPB and during the early postoperative period. This effect seems to be due to a redistribution of interstitial fluid to the intravascular space, possibly decreasing tissue edema. CONCLUSION. The hypertonic saline HES solution adds a new dimension to volume therapy for cardiac surgery patients. The improvement in hemodynamics was effective and not only transient. Fluid requirements were significantly reduced during as well as after CPB, and pulmonary gas exchange was least compromised in these patients.

Aged↗
PubMed1987

Aortic endothelial cell proteoheparan sulfate. II. Modulation by extracellular matrix.

The effects of extracellular matrix components on proteoheparan sulfate biosynthesis was studied for bovine aortic endothelial cells in tissue culture. When the cells were maintained on a variety of different purified components of the extracellular matrix, the cells expressed the same three species of proteoheparan sulfates as the cells cultured on tissue culture plastic (HS I, HS II, and HS III). However, the amounts of the three species recovered from the tissue culture medium were found to be dependent on the substrate on which the cells are grown as well as on other factors. In comparison with plastic, much less HS I was found in the medium of cells maintained on substrates containing diverse matrix molecules, whereas the amounts of HS II and HS III essentially remained the same. In contrast, when bovine aortic organ cultures were analyzed under pulsatile flow, marked differences in the profile of proteoheparan sulfate biosynthesis were observed: HS I was found exclusively associated with the plasma membrane of the endothelial cells; HS II was localized only to the subendothelial matrix; and HS III represented the only proteoheparan sulfate species in the medium. This distribution is consistent with polarized secretion and deposition into the subcellular matrix of HS III and retention of HS I in the plasma membrane in the organ culture situation, a biosynthetic phenotype which can only be approximated at best by maintaining the endothelial cells on a substrate other than plastic. When aortic media (devoid of endothelial cells) was placed in organ culture, no HS III could be detected, which suggested that the vascular endothelial cell is the major cell type responsible for its synthesis in organ culture. Thus, the extracellular matrix, depending upon its composition and organization, may play an important role in stabilizing cell polarity and thereby contribute to maintenance of the differentiated phenotype appropriate for the endothelial cell.

Animals↗
PubMed1984

Metastatic melanoma cell heparanase. Characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase.

Heparan sulfate (HS), a prominent component of vascular endothelial basal lamina, is cleaved into large Mr fragments and solubilized from subendothelial basal lamina-like matrix by metastatic murine B16 melanoma cells. We have examined the degradation products of HS and other purified glycosaminoglycans produced by B16 cells. Glycosaminoglycans 3H-labeled at their reducing termini or metabolically labeled with [35S]sulfate were incubated with B16 cell extracts in the absence or presence of D-saccharic acid 1,4-lactone, a potent exo-beta-glucuronidase inhibitor, and glycosaminoglycan fragments were analyzed by high speed gel permeation chromatography. HS isolated from bovine lung, Engelbreth-Holm-Swarm sarcoma, and subendothelial matrix were degraded into fragments of characteristic Mr, in contrast to hyaluronic acid, chondroitin 6-sulfate, chondroitin 4-sulfate, dermatan sulfate, keratan sulfate, and heparin which were essentially undegraded. Heparin, but not other glycosaminoglycans, inhibited HS degradation. The time dependence of HS degradation into particular Mr fragments indicated that HS was cleaved at specific intrachain sites. In order to determine specific HS cleavage points, HS prereduced with NaBH4 was incubated with a B16 cell extract and HS fragments were separated. The newly formed reducing termini of HS fragments were then reduced with NaB[3H]4, and the fragments hydrolyzed to monosaccharides by trifluoroacetic acid treatment and nitrous acid deamination. Since 3H-reduced terminal monosaccharides from HS fragments were overwhelmingly (greater than 90%) L-gulonic acid, the HS-degrading enzyme responsible is an endoglucuronidase (heparanase).

Animals↗
PubMed1995

Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata.

This study determined differences of fascia dentata (FD) peptide and inhibitory neuroanatomy between patients with epileptogenic hippocampal sclerosis (HS), those with extrahippocampal seizure pathologies, and autopsy comparisons. Surgically treated temporal lobe epilepsy patients were clinically classified into two pathogenic categories: (1) HS with focal mesial temporal neuroimaging and histories of initial precipitating injuries to the brain (n = 18) and (2) non-HS patients with extrahippocampal mass lesions or idiopathic seizures (i.e., without lesions or HS; mass lesion/idiopathic; n = 9). The hippocampal sections were studied for (1) granule cell, hilar, CA4, and CA3 neuron densities; (2) hilar densities and the percentage of neurons immunoreactive (IR) for neuropeptide Y (NPY), somatostatin (SS), and glutamate decarboxylase (GAD); (3) densities of GAD neurons in the lower granule cell and infragranular zone (basket-like cells); (4) the semiquantitative pattern of IR peptides/GAD FD molecular layer axon sprouting; (5) IR gray values (GV) of the FD molecular layers; and (6) the thickness of the supragranular molecular layer. Results showed the following. (1) Compared to autopsies, both HS and mass lesion/idiopathic patients showed less granule cell and CA3 neuron densities, but there were no statistical differences between the latter two pathogenic categories. (2) By contrast, compared to autopsies and mass lesion/idiopathic cases, HS patients showed less hilar and CA4 neuron densities, and there were no differences between autopsies and mass lesion/idiopathic. (3) Compared to autopsies, the NPY and SS hilar neuron densities in HS patients, but not mass lesion/idiopathic cases, were less. (4) Compared to autopsies, the hilar GAD neuron densities for HS and mass lesion/idiopathic patients were not less. (5) In HS patients the averaged percentages of hilar SS neurons were less than autopsies, and no other differences of IR hilar percentages were found. (6) The densities of GAD basket-like neurons and the thickness of the supragranular molecular layer were not different between any combination of pathogenic categories and autopsies. (7) By semiquantitative visual assessments, peptides/GAD axon sprouting into the FD was greater in HS compared to mass lesion/idiopathic or autopsies. (8) Compared to mass lesion/idiopathic cases, in HS NPY outer molecular layer GVs were lower, SS GVs were not different, and GAD inner molecular layer GVs were higher. (9) Analyses comparing the two pathogenic categories and neuron densities with peptides/GAD axon sprouting found six comparisons that correlated sprouting with hilar and CA4 neuron losses, and four comparisons showing greater sprouting in HS compared to mass lesion/idiopathic.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1996

Effect of heat shock and endotoxin stress on enterocyte viability apoptosis and function varies based on whether the cells are exposed to heat shock or endotoxin first.

BACKGROUND: Stress-gene responses, including the heat shock (HS) response and the acute phase response, are protective mechanisms for cells after exposure to stress. Both responses cannot occur simultaneously, and, in endothelial cells, the sequence of stress-gene expression seems to be a critical factor in whether cellular protection or injury occurs. OBJECTIVE: To determine if the sequence of stress-gene expression affects cellular protection or injury in epithelial cells. DESIGN: Randomized controlled in vitro study. SETTING: University research laboratory. SUBJECTS: Rat intestinal epithelial cell-6 (IEC-6) cells were grown on 35-mm culture dishes, chamber slides, or in a bicameral system to confluence or until tight junction integrity was established. INTERVENTIONS: Rat IEC-6 cells were examined for viability, apoptosis, and bacterial translocation (BT) after exposure to 25-micrograms/mL lipopolysaccharide (LPS) for 18 hours to HS (43 degrees C) for 90 minutes, to LPS followed by HS, or to HS followed by LPS. MAIN OUTCOME MEASURES: The IEC-6 cells were stained for viability and apoptosis using trypan blue and a direct immunoperoxidase detection of digoxigenin-labeled genomic DNA (Apop Tag Plus In Situ Apoptosis Detection Kit, Oncor, Gaithersburg, Md), respectively. Bacterial translocation was measured by culturing the bacteria (ie, Escherichia coli) that crossed the IEC-6 cell monolayer in the bicameral system. RESULTS: Control cells (medium only) and cells exposed to LPS alone, HS alone, or HS followed by LPS had a viability from 92% to 98%, and the percentage of apoptotic cells ranged from 2.2% to 5.7%. In contrast, IEC-6 cells exposed to LPS followed by HS had a significantly lower viability (83%, P < .05 vs all other groups) and a higher percentage of apoptotic cells (12.2%, P < .01). At 3 hours after challenge with E coli, the LPS-exposed IEC-6 cell monolayers had significantly increased BT vs control monolayers (P < .05), while the IEC-6 cell monolayers exposed to HS followed by LPS had decreased BT (P < .05). Conversely, cells exposed to LPS followed by HS had the highest magnitude of BT (P < .01 vs all other groups). CONCLUSIONS: These results indicate that preinduction of HS response can diminish LPS-induced cell injury, while induction of HS response after the LPS challenge (ie, the acute phase response) may lead to decreased enterocyte viability, increased apoptosis, and cellular dysfunction as manifested by BT.

Acute-Phase Reaction↗
PubMed1999

Short echo time single-voxel 1H magnetic resonance spectroscopy in magnetic resonance imaging-negative temporal lobe epilepsy: different biochemical profile compared with hippocampal sclerosis.

Single-voxel proton magnetic resonance spectroscopy (1H MRS) has shown abnormalities in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). Many TLE patients, however, do not have HS or other lesions on quantitative magnetic resonance imaging (MRI) (MRI-negative). Fifteen control subjects, 15 patients with unilateral HS, and 15 MRI-negative TLE patients underwent 1H MRS at an echo time of 30 msec on a 1.5-T GE Signa scanner. Voxels were tailored to the individual hippocampi. N-Acetylaspartate (NAA), creatine, choline, total glutamate plus glutamine (Glx), and myo-inositol (Ins) were quantitated by using an external standard and LCModel, a user-independent quantitation method. Normal ranges were defined as the control mean +/- 2.5 SD. In HS patients, 12 of 15 had abnormally low NAA in sclerotic hippocampi; 3 of these 12 also had abnormally low NAA contralaterally. Abnormally low NAA/Ins ratios lateralized the side affected by HS in 7 of 15 patients, without any bilateral abnormalities. In 15 MRI-negative TLE patients, 4 had abnormally low hippocampal NAA ipsilateral to seizure onset, 1 of whom had abnormally low NAA bilaterally. Analysis of groups of subjects showed a bilateral decrease in NAA, most marked in patients with HS and on the side of seizure onset. The mean NAA/Ins ratio was lower in patients with HS than in control subjects and in MRI-negative patients. The concentration of Glx was higher ipsilateral to seizure onset in MRI-negative patients than in HS patients. Quantitative short echo time 1H MRS identified abnormalities in 87% of patients with HS and 27% of MRI-negative TLE patients in concordance with other lateralizing data. In individual and group comparisons, 1H MRS described a metabolite profile in the hippocampi of MRI-negative TLE patients that was different from patients with HS, with an increase in Glx and a less marked decrease in NAA than was seen in HS.

Adult↗
PubMed2007

Heparan sulfate regulates the anabolic activity of MC3T3-E1 preosteoblast cells by induction of Runx2.

The transcription factor Runx2 can be controlled by a number of upstream regulators involved in intracellular signalling, including the activation ERK1/2 signaling by fibroblast growth factor-2 (FGF-2). FGFs interact with their cell surface receptors (FGFRs) through an obligate cross-binding interaction with heparan sulfate proteoglycan (HSPG) co-receptors; exogenous HS sugar chains have been shown to potently modulate changes in cell phenotype depending on the stage of tissue differentiation when the HS is harvested, suggesting that HS chain structure and function varies depending on the stage of cell maturity. This study examined the potential of bone-derived heparan sulfate (HS), harvested from differentiating osteoblasts, for the enhancement of preosteoblast growth and differentiation. HS was harvested from conditioned media, cell surface and matrix compartments of postconfluent (differentiating) MC3T3-E1 osteoblasts and dosed back onto preconfluent MC3T3-E1 cells. We show that HS can increase the expression Runx2, ALP, and OPN in preosteoblast cells, suggesting the potential for exogenous HS to shift cells from proliferative to differentiative phenotypes. In line with their structural differences, only HS released into the media was found to co-stimulate the mitogenic effect of FGF-2, whilst exogenous application of all the HSs together with FGF-2 served to increase the expression of OPN. Only the application of cell surface-derived HS triggered a synergistic increase in FGFR1 expression together with FGF-2, although all three HS preparations could trigger transient increases in PI3K, ERK1/2, and stat3 phosphorylation levels. These findings demonstrate that the compartmentally distinct HS species expressed by differentiating MC3T3-E1 cells act in complex ways to coordinate the extracellular conditions that lead to osteoblast differentiation, with the cell surface species coordinating the FGF response.

Alkaline Phosphatase↗
PubMed2000

Hepatic integrity dependent on matrix metalloproteinase inhibition, not tumor necrosis factor alpha or different bleeding rates.

Discrepancies in the levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) following hemorrhagic shock (HS) may be due to the inconsistent rates of bleeding. The purpose of this study was to investigate the effects of rapid versus slow bleeding rates on TNF-alpha levels and if inhibition of TNF-alpha convertase by a matrix metalloproteinase inhibitor (MMPI) affects hepatic integrity in animals exposed to 35% HS. Sprague-Dawley male rats (n = 24, 300-350 g) were divided into four groups: HS 15 (produced over 15 min), HS 30 (produced over 30 min), and HS with MMPI (2.5 mg/kg British Biotech 1101: HS15 + MMPI, HS30 + MMPI). Mean arterial blood pressure (MAP), serum TNF-alpha,levels, and hepatic resting membrane potentials (E(m)) were obtained. A Student t test was performed. TNF-alpha levels for HS 15, HS15 + MMPI, HS 30, and HS 30 + MMPI were 474, 40, 32, and 50 pg/ml, respectively. The hepatic resting membrane potentials for HS 15, HS15 + MMPI, HS 30, and HS 30 + MMPI were -26, -30, -23, and -31 mV, respectively. In conclusion, circulating TNF-alpha levels are affected by the rate of bleeding in hemorrhagic shock. However, despite the differences in the magnitude of TNF-alpha in untreated animals, hepatic integrity was compromised. Interestingly, MMPI, an inhibitor of TNF-alpha convertase, stabilizes the membrane potential in both types of hemorrhagic shock.

ADAM Proteins↗
PubMed2002

Aging abolishes the cardioprotective effect of combination heat shock and hypoxic preconditioning in reperfused rat hearts.

Hypoxic preconditioning (HP) does not improve post-ischemic function in the hearts of aging rats secondary to failure of protein kinase C (PKC) activation, but the effect of heat shock (HS) or preconditioning has not been studied. We studied whether HS increases tolerance to ischemia and whether its combination with HP would restore the cardioprotective effect in aging rat hearts. HS was performed in 12- and 50-week-old rats. Hearts were isolated and subjected to HP by 10 min hypoxic perfusion before 25 min ischemia followed by 30 min reperfusion 48 h after HS. Both HP and HS improved recovery of left ventricular function with translocation of PKC-delta from the cytosol to the nuclear fraction and induction of heat shock proteins, HSP27, HSP70, and alphaB-crystallin. The combination of HS and HP enhanced the translocation of PKC-delta in young rats, resulting in further improvement in functional recovery. In older rats, HP translocated PKC-delta from the membrane to the cytosol fraction, but did not improve functional recovery, although the combination of HS with HP induced HS proteins and translocated PKC-delta from the cytosol to the nuclear fraction. HS provided cardioprotection and had additive effects to HP with additional PKC-delta activation in young rats. However, in hearts from aging rats, HS alone was not cardioprotective, nor was its combination with HP, despite the induction of HS proteins and the activation of PKC-delta, resulting in its translocation to the nuclear fraction.

Aging↗
PubMed2005

Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses.

Glycosaminoglycans are accumulated in both mucopolysaccharidoses (MPS) and mucolipidoses (ML). MPS I, II, III and VII and ML II and ML III patients cannot properly degrade heparan sulphate (HS). In spite of the importance of HS storage in the metabolic pathway in these diseases, blood and urine HS levels have not been determined systematically using a simple and economical method. Using a new ELISA method using anti-HS antibodies, HS concentrations in blood and urine were determined in MPS and ML II and ML III patients. HS concentrations were determined in 156 plasma samples from MPS I (n = 23), MPS II (n = 26), MPS III (n = 24), MPS IV (n = 62), MPS VI (n = 5), MPS VII (n = 5), ML II (n = 8) and ML III (n = 3), and 205 urine samples from MPS I (n = 33), MPS II (n = 33), MPS III (n = 30), MPS IV (n = 82), MPS VI (n = 7), MPS VII (n = 9), ML II (n = 8) and ML III (n = 3). The ELISA method used monoclonal antibodies against HS. MPS I, II, III and VII and ML II and III patients had significant elevation in plasma HS, compared to the age-matched controls (p < 0.0001). Eighty-three out of 89 (93.3%) of individual values in the above MPS types and ML were above the mean +2SD of the controls. In urine samples, 75% of individual values in patients with those types were above the mean +2SD of the controls. In contrast to the previous understanding of the HS metabolic pathway, plasma HS levels in all five MPS VI and 15% of MPS IV patients were elevated above the mean +2SD of the controls. These findings suggest that HS concentration determined by ELISA, especially in plasma, could be a helpful marker for detection of the most severe MPS I, II, III, VI and VII and ML II, distinguishing them from normal populations.

Adolescent↗
PubMedDate not supplied

"Magnetic resonance imaging negative positron emission tomography positive" temporal lobe epilepsy: FDG-PET pattern differs from mesial temporal lobe epilepsy.

PURPOSE: Some patients with temporal lobe epilepsy (TLE) lack evidence of hippocampal sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would have a different pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with evidence of hippocampal atrophy on magnetic resonance imaging (MRI) (HS+ve), with a lateral temporal neocortical rather than mesial focus. PROCEDURES: Thirty consecutive HS-ve patients and 30 age- and sex-matched HS+ve patients with well-lateralized EEG were identified. FDG-PET was performed on 28 HS-ve patients and 24 HS+ve patients. Both groups were compared using statistical parametric mapping (SPM), directly and with FDG-PET from 20 healthy controls. RESULTS: Both groups showed lateralized temporal hypometabolism compared to controls. In HS+ve, this was antero-infero-mesial (T = 17.13); in HS-ve the main clustering was inferolateral (T = 17.63). When directly compared, HS+ve had greater hypometabolism inmesial temporal/hippocampal regions (T = 4.86); HS-ve had greater inferolateral temporal hypometabolism (T = 4.18). CONCLUSIONS: These data support the hypothesis that focal hypometabolism involves primarily lateal neocortical rather than mesial temporal structures in 'MRI-negative PET-positive TLE.'

Adult↗