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Biomedical subjects

C Forster

Publications and source records attributed to C Forster.

At least 19 recordsLinked to original sources
PubMed2006

Cerebral representation of the anorectum using functional magnetic resonance imaging.

BACKGROUND: Anorectal continence depends not only on the organs of continence but also on cerebral control. There are relatively few data regarding cerebral processing of anorectal continence. METHODS: Thirteen healthy subjects underwent rectal distension to cause urge increasing to discomfort during functional magnetic resonance imaging (fMRI). In addition, a painful heat stimulus was applied to the skin of the anterior abdominal wall in the dermatome corresponding to the rectum. Voluntary contraction of the anal sphincter was also performed. Subjective rating of stimulus intensity was recorded. Evaluation of the data used a general linear model with Brain Voyager(trade mark). RESULTS: Subjective sensation of discomfort increased during repeated rectal distension and caused activation in the anterior cingulate gyrus, insula, thalamus and secondary somatosensory cortex seen on fMRI. Perception of rectal urge and discomfort activated the same cerebral regions with differing intensity. Application of a painful thermal stimulus in the corresponding dermatome showed a modification of the response. Voluntary contraction of the anal sphincter led to activation of the motor cortex and increased activity in the supplementary motor cortex and the insula. CONCLUSION: Cerebral representation of the anorectum as mapped by fMRI is intricate and reflects the complexity of the continence mechanism.

Adult↗
PubMed2006

Capsaicin-induced local elevations in collagenase-2 (matrix metalloproteinase-8) levels in human gingival crevice fluid.

BACKGROUND AND OBJECTIVES: Application of capsaicin on alveolar mucosa provokes pain and neurogenic vasodilatation in the adjacent gingiva. Pain-associated inflammatory reactions may initiate expression of several pro-inflammatory mediators. Collagenase-2 (matrix metalloproteinase-8: MMP-8) is the major destructive protease, especially in the periodontitis-affected gingival crevice fluid (GCF). With this background, we wished to study whether capsaicin stimulation of alveolar mucosa can induce changes in the GCF MMP-8 levels. MATERIAL AND METHODS: For 10 generally and periodontally healthy human volunteers, capsaicin (3%)-moistened filter paper was applied unilaterally to the buccal alveolar mucosa on the anterior maxilla. GCF samples were collected from the tooth at the stimulation site and from several other incisors in the upper jaw. MMP-8 levels and molecular forms in GCF samples were determined by immunofluorometric assay (IFMA) and western immunoblotting, respectively. RESULTS: Capsaicin stimulation of the alveolar mucosa induced significant local elevations in levels and activation of MMP-8 in GCF of the adjacent teeth. Western immunoblot revealed that both neutrophil- and mesenchymal-type MMP-8 isoforms were elevated and activated, together with 110 kDa high-molecular size MMP-8 species. This capsaicin-evoked MMP-8 elevation lasted several minutes after stimulation. During the experiments, no marked changes occurred in MMP-8 levels in the GCF of distantly located teeth. CONCLUSIONS: These results suggest that capsaicin-evoked neurogenic gingival inflammation can trigger the expression and activation of MMP-8 in GCF of the adjacent teeth.

Adult↗
PubMed2005

Cortical representation of experimental tooth pain in humans.

Cortical processing of electrically induced pain from the tooth pulp was studied in healthy volunteers with fMRI. In a first experiment, cortical representation of tooth pain was compared with that of painful mechanical stimulation to the hand. The contralateral S1 cortex was activated during painful mechanical stimulation of the hand, whereas tooth pain lead to bilateral activation of S1. The S2 and insular region were bilaterally activated by both stimuli. In S2, the center of gravity of the activation during painful mechanical stimulation was more medial/posterior compared to tooth pain. In the insular region, tooth pain induced a stronger activation of the anterior and medial parts. The posterior part of the anterior cingulate gyrus was more strongly activated by painful stimulation of the hand. Differential activations were also found in motor and frontal areas including the orbital frontal cortex where tooth pain lead to greater activations. In a second experiment, we compared the effect of weak with strong tooth pain. A significantly greater activation by more painful tooth stimuli was found in most of those areas in which tooth pain had induced more activation than hand pain. In the medial frontal and right superior frontal gyri, we found an inverse relationship between pain intensity and BOLD contrast. We concluded that tooth pain activates a cortical network which is in several respects different from that activated by painful mechanical stimulation of the hand, not only in the somatotopically organized somatosensory areas but also in parts of the 'medial' pain projection system.

Adult↗
PubMed2005

Tau suppression in a neurodegenerative mouse model improves memory function.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.

Aging↗
PubMed2005

Painful tooth stimulation elevates matrix metalloproteinase-8 levels locally in human gingival crevicular fluid.

Recent studies have demonstrated that pulpal pain can induce neurogenic inflammatory reactions in gingiva and the expression of pro-inflammatory neuropeptides in gingival crevicular fluid (GCF). Neuropeptides co-ordinate the activity of immuno-effector cells and may influence the secretion of matrix metalloproteinase (MMP)-8, the major tissue-destructive protease in GCF. With this background, we studied whether experimental pulpal pain can trigger changes in GCF MMP-8 levels. The molecular forms of MMP-8 in the GCF of stimulated and non-stimulated teeth were analyzed by Western immunoblot, and MMP-8 levels by quantitative immunofluorometric assay. Painful stimulation of the upper incisor provoked significant elevations in GCF MMP-8 levels of the stimulated tooth. Western immunoblot revealed elevations in both neutrophil- and mesenchymal-type MMP-8 isoforms. At the same time, the GCF MMP-8 levels of the non-stimulated teeth were not changed. Analysis of these data indicated that pulpal pain can induce local elevations in MMP-8 levels in GCF.

Adult↗
PubMed2003

BOLD effects in different areas of the cerebral cortex during painful mechanical stimulation.

The contribution of four cortical areas (S1, S2, insular cortex and gyrus cinguli) to pain processing was assessed by functional magnetic resonance imaging (fMRI). Phasic (mechanical impact) and tonic stimuli (squeezing) were applied to the back of a finger, both at two different strengths. Stimuli were adjusted to inflict weak and strong pain sensations. It had been shown before that stronger noxious mechanical stimuli induce a weaker input from myelinated mechanoreceptors, but a more vigorous input from nociceptive primary afferents, and vice versa. Sizes of activation clusters and percent increase of the blood oxygenation level dependent (BOLD) signal during activation were compared in the areas of interest. Phasic stimulus patterns were more closely reflected in the time course of the MR signal in S1, S2 and the cingulate than tonic patterns, since the tonic stimuli tended to induce slow MR signal increase also during the resting periods which is in parallel to the persisting character of the tonic pain sensations. In S1 only the contralateral side was activated in most cases, and the more painful stimuli did not induce greater BOLD responses compared to the less painful stimuli in this area. Paradoxically, more painful stimuli produced smaller activation clusters in S1, both in tonic and phasic stimulus trials. In contralateral S2 more painful phasic stimuli induced significantly stronger BOLD responses than the weaker stimuli. The responses to tonic stimuli did not differentiate painfulness and were significantly smaller than the phasic. Activation clusters in this area were also smaller for tonic stimuli. In the gyrus cinguli more painful phasic stimuli induced stronger BOLD responses, but no difference was seen between tonic stimulation of different strength. Though the insular cortex was often bilaterally activated, no significant differences between stimulus quality or intensity were found. Our results provide evidence for a contribution of the S2 projection area and of the cingulate cortex to the processing of the intensity dimension of phasic mechanical pain. Such evidence was not found for the S1 area, which probably receives dominant input from non-nociceptive mechanoreceptors.

Adult↗
PubMed2003

Low-threshold heat receptor in chick sensory neurons is upregulated independently of nerve growth factor after nerve injury.

In mammals, the cloned low-threshold heat receptor, vanilloid receptor subtype 1 (VR1), is involved in the genesis of thermal hyperalgesia after inflammation. However, there is evidence that VR1 is not involved in the thermal hyperalgesia that occurs after nerve injury. In search for other heat receptors which might be involved in this phenomenon, we previously demonstrated that chick dorsal root ganglion neurons, which are insensitive to capsaicin, respond to low-threshold heat. Here, we investigated whether expression of the low-threshold noxious heat receptor in chicks is regulated by nerve growth factor (NGF), as VR1 is in mammals. Heat (44 degrees C) responsiveness of isolated dorsal root ganglion neurons of chicks was investigated (i) under culture conditions for up to 4 days with and without NGF and (ii) after a tight ligation of the sciatic nerve for up to 6 days, using cobalt-uptake method. In every case, a significant upregulation in the proportion of heat-responsive neurons was observed. On the molecular level, there was an increase of chick VR1 mRNA level in dorsal root ganglion cells cultured for 3 days in medium lacking NGF. In rat dorsal root ganglion neurons cultured for 1-4 days without NGF, patch-clamp experiments revealed that after 1 day almost all neurons responding to heat also responded to capsaicin, whereas after 3-4 days, more than one-half of the heat-responsive neurons did not respond to capsaicin. These data suggest the existence of low-threshold heat receptors in chick dorsal root ganglion neurons, the expression of which is regulated independently of NGF.

Animals↗
PubMed2003

Laser capture microdissection and real-time PCR for analysis of glomerular endothelin-1 gene expression in mesangiolysis of rat anti-Thy 1.1 and murine Habu Snake Venom glomerulonephritis.

Molecular analysis of pathologic changes in glomeruli requires methods allowing rapid and exact detection of alterations in gene expression. Here, we analyzed endothelin-1 (ET-1) mRNA expression in mesangiolytic glomeruli during the course of a rat and murine model of mesangioproliferative glomerulonephritis (GN). A novel method combining laser capture microdissection (LCM), which permits the precise removal of selected mesangiolytic glomeruli, with a highly sensitive real-time RT-PCR technique was used. Anti-Thy 1.1. GN was introduced in male Sprague-Dawley rats (1.0 mg/kg body weight of OX-7 IV) and Habu Snake Venom GN was introduced in C57BL6 mice (habu snake venom toxin 6 mg/kg body weight IV). The degree of mesangiolysis during both GNs was analyzed using a semiquantitative scoring system. Mesangiolytic glomeruli were microdissected at different days of the diseases (day 2, 6, and 12 in anti-Thy 1.1 GN and days 1, 3, 7, and 14 in Habu Snake Venom GN) and from normal control animals. After RNA extraction and cDNA synthesis, ET-1 gene expression was measured by real-time RT-PCR. In parallel, in anti-Thy 1.1. GN ET-1 mRNA expression was analyzed using semiquantitative nonradioactive in situ hybridization; ET-1 protein expression was investigated by immunohistochemistry. Mesangiolysis peaked at day 6 in anti-Thy1.1 GN and at day 1 in Habu Snake Venom GN. Mesangiolytic glomeruli were easily microdissected on cryostat sections in both models; quantification of mRNA with RT-PCR was reliable and reproducible. Glomerular ET-1 mRNA expression increased during the course of anti-Thy 1.1 GN and Habu Snake Venom GN peaked when mesangiolysis was most pronounced. This was seen by RT-PCR after glomerular LCM and by in situ hybridization; in parallel, glomerular ET-1 protein expression was increased. Combination of LCM and RT-PCR is a reliable method for quantification of localized gene expression in isolated renal structures. The above data argue for an important role of ET-1 in pathogenesis and/or repair of mesangiolysis in experimental mesangioproliferative GN.

Animals↗
PubMed2003

Factors associated with coronary artery calcification in young female patients with SLE.

BACKGROUND: With improved survival rates of patients with systemic lupus erythematosus (SLE), damage such as accelerated atherosclerosis gains increasing importance. OBJECTIVE: To identify the prevalence of coronary artery calcifications (CAC) in asymptomatic patients. METHODS: Electron beam tomography (EBT) was performed in 75 female patients with SLE aged <50. The results were correlated with traditional and SLE related factors associated with CAC. 49 women with symptomatic coronary heart disease (CHD) and 279 women without CHD were also analysed. RESULTS: Overall, 21/75 (28%) patients had CAC. Low HDL cholesterol levels <1.40 mmol/l (p=0.03, OR=1.8, 67% v 39%) and cigarette smoking (p=0.01, OR=5.7, 76% v 44%) were identified as factors associated with CAC. Hypertension and high cholesterol were more common in women with CHD (p<0.01) than in those without CHD. SLE related factors were proteinuria (1331 v 465 mg/day, p=0.02), impaired renal function (p=0.02, OR=2.6, 26% v 6%), and high C3 levels (p=0.04, OR=1.8, 65% v 38%). High C3 levels were also more common in symptomatic CHD (p=0.02). The prevalence of Sm antibodies was lower in patients with CAC (15% v 42%, p=0.03). In a multivariate analysis, cigarette smoking, reduced renal function, high C3, and a cumulative steroid dose above 30 g were the most important CAC associated factors in the lupus cohort. CONCLUSION: A subgroup of patients with SLE with CAC without any clinical symptoms of CHD was identified by EBT. Therefore, EBT is useful for assessing asymptomatic atherosclerosis in this group.

Adult↗
PubMed2003

Differences between tooth stimulation and capsaicin-induced neurogenic vasodilatation in human gingiva.

Animal experiments have shown that the application of capsaicin to oral mucosa leads to a neurogenic inflammation associated with blood flow elevations in gingivomucosal tissues. In this investigation, we measured the tooth stimulation and capsaicin-evoked blood flow responses in maxillary gingiva in humans to study whether axon-reflex-mediated vasodilatation crosses the midline of the maxilla. The vasoactive reactions were mapped by laser Doppler imaging. Unilateral stimulation of alveolar mucosa and attached gingiva by capsaicin evoked a distinct neurogenic vasodilatation in ipsilateral gingiva, which rapidly attenuated at the midline. Capsaicin stimulation of alveolar mucosa provoked clear inflammatory reactions. In contrast to capsaicin stimuli, tooth stimulation produced symmetrical vasodilatations bilaterally in the gingiva. The ipsilateral responses were significantly smaller during tooth stimulation than during capsaicin stimuli. Analysis of these data suggests that capsaicin-induced inflammatory reactions in gingivomucosal tissues do not cross the midline in the anterior maxilla. The enhanced reaction found during stimulation of alveolar mucosa indicates that alveolar mucosa is more sensitive to chemical irritants than attached gingiva.

Adult↗
PubMed2001

Blood flow increase in the human lip after high-intensity tooth stimulation is not based on cholinergic mechanisms.

The purpose of this study was to investigate whether parasympathetic cholinergic pathways are involved in the regulation of orofacial blood flow. The effect of atropin (1 mg, iv.) on blood flow responses in the lower lip, nose and hand during painful tooth stimulation was studied in healthy human subjects (n=8). In all subjects, tooth stimulation caused a long lasting vasodilatation in the lower lip. During stimulation there was a transient elevation in heart rate (HR) and blood pressure (BP) concomitantly with a blood flow decrease in the finger and nose. With atropin, the pain-induced HR and BP elevations and blood flow reductions in the nose and finger were decreased. However, the pain-induced blood flow increase in the lip was not changed. This study indicates that the tooth stimulation-induced vasodilatation in the lip is not based on parasympathetic cholinergic mechanisms.

Atropine↗
PubMed2001

Structural alterations of adhesion mediating components in cells cultured on poly-beta-hydroxy butyric acid.

Polymers may serve as a biodegradable material in tissue engineering. To assess the biocompatibility of poly-beta-hydroxy butyric acid (PHB), we studied the structural organization of cellular molecules involved in adhesion using osteoblastic and epithelial cell lines. On PHB, both cell lines revealed a rounded cell shape due to reduced spreading. The filamentous organization of the actin cytoskeleton was impaired. In double immunofluorescence analyses we demostrated that the colocalization of the fibronectin fibrils with the actin filaments was lost in cultures on PHB. Similarly, collagen II distribution was altered, whereas the organization of collagen I was not obviously affected. Further evidence for impaired structural organization was obtained for the beta1-integrin receptor and vinculin which mediate the interaction of the cytoskeleton with the extracellular matrix. In confluent epithelial cells, the tight junction protein ZO-1 showed a larger lateral extension in the cell-cell contacts when cells were grown on PHB. Because structural organization of components which mediate cell-matrix and cell-cell adhesion controls cell physiology these parameters could be a sensitive indicator for the biocompatibility of implant materials.

Actins↗
PubMed2001

The importance of stimulus site and intensity in differences of pain-induced vascular reflexes in human orofacial regions.

Studies in anaesthetized animals have indicated that noxious stimulation may produce marked blood flow changes in various orofacial structures, but the influence of painful stimulation on the blood flow regulation of the orofacial area of humans has been studied only to a limited extent. The purpose of this investigation was to study whether there are differences in temporal and spatial patterns of pain-induced vasoactive reflexes between various orofacial regions and hand in healthy human volunteers. Dynamic changes in blood flow in various orofacial regions elicited by painful stimulation of the tooth and finger were measured by means of Laser Doppler imaging (LDI) and computer-assisted infrared thermography (IRT). Blood flow of the finger was recorded by laser Doppler flowmetry (LDF) and plethysmography (PLET). During both stimulus paradigms there was a transient elevation in heart rate (HR) and blood pressure (BP). At the same time there was a significant blood flow decrease in the finger (LDF, PLET) and in the nose (LDI, IRT). In contrast to tooth stimulation, finger stimulation caused a more marked blood flow reduction in the finger. Only high intensity tooth stimulation, but not finger stimulation, caused a long-lasting vasodilatation both in lower and upper lip. The blood flow changes in the lips were not correlated with changes in systemic blood pressure or heart rate. In the cheek, there were no marked flow changes during either finger or tooth stimulation. These data indicate that painful tooth (regional) stimulation, but not finger (remote) stimulation, can induce a long-lasting vasodilatation in parts of orofacial tissues which cannot be explained by changes in central cardiovascular parameters. This tooth-stimulation-induced blood flow increase supports the hypothesis of a special vasodilator reflex mechanism in the orofacial area. Furthermore, tooth-stimulation-induced vasoconstriction in the nose and dilatation in the lips indicate that separate vasoactive reflex mechanisms may exist for different orofacial regions.

Adult↗
PubMed2001

Results of surgery in patients with refractory extratemporal epilepsy with normal or nonlocalizing magnetic resonance findings investigated with subdural grids.

PURPOSE: To study the efficacy of extensive coverage of the brain surface with subdural grids in defining extratemporal cortical areas amenable for resection in patients with refractory extratemporal epilepy (R-ExTE) and normal or nonlocalizing magnetic resonance imaging (MRI) scans. METHODS: Sixteen patients with R-ExTE were studied. Eleven patients had simple partial, eight had complex partial, and three had supplementary motor area seizures. Seizure frequency ranged from three per month to daily episodes. Interictal EEG showed large focal spiking areas in 11 patients, secondary bilateral synchrony in four, and was normal in one patient. Surface ictal recordings were nonlocalizing in six patients, and in 10, they disclosed large ictal focal spiking areas. MRI was normal in 10 patients, and in six patients, focal nonlocalizing potentially epileptogenic lesions were found. All patients were given an extensive coverage of the cortical convexity with subdural electrodes through large unilateral (n = 13) or bilateral (n = 3) craniotomies. Bipolar cortical stimulation was carried out through the implanted electrodes. RESULTS: Interictal invasive recording findings showed widespread spiking areas in 13 patients and secondary bilateral synchrony in three. Ictal invasive recordings showed focal seizure onset in all patients. There were six frontal, two parietal, one temporooccipital, four rolandic, and three posterior quadrant resections. Thirteen patients had been rendered seizure free after surgery, and three had > or =90% of seizure-frequency reduction. Pathologic findings included gliosis (n = 10), cortical dysplasia (n = 5), or no abnormalities (n = 1). Six patients had transient postoperative neurologic morbidity. CONCLUSIONS: Extensive subdural electrodes coverage seems to be an effective way to investigate patients with R-ExTE and normal or nonlocalizing MRI findings.

Adolescent↗
PubMed2001

Cyclooxygenase-2 inhibitor ns-398 protects neuronal cultures from lipopolysaccharide-induced neurotoxicity.

BACKGROUND AND PURPOSE: The prostanoid-synthesizing enzyme cyclooxygenase (COX)-2 is markedly upregulated after cerebral ischemia and may participate in the mechanisms by which postischemic inflammation contributes to the late stages of ischemic brain injury. In the present study, we sought to provide additional evidence for a role of COX-2 in the mechanisms of neurotoxicity associated with inflammation. METHODS: Nine-day-old neuronal-glial cultures, prepared from the cerebral cortex of newborn C57BL/6J mice, were exposed to lipopolysaccharide (LPS), a potent proinflammatory agent. The contribution of COX-2 was investigated by using the COX-2 inhibitor NS-398. RESULTS: LPS produced a dose-dependent (0.001 to 10 microg/mL) and selective neuronal death that was well developed 72 hours after treatment. The effect was associated with a marked increase in the concentration of the COX reaction product prostaglandin E(2) (PGE(2)) and of the cytokine tumor necrosis factor-alpha (TNF-alpha). NS-398 (10 micromol/L) blocked the PGE(2) increase, attenuated the TNF-alpha increase, and prevented the neuronal death produced by LPS. TNF-alpha-blocking antibodies attenuated LPS-induced neuronal death, but the protection was less pronounced than that afforded by NS-398. LPS failed to elevate PGE(2) or to produce cell death in neuron-enriched cultures, suggesting that glial cells are required for these effects. CONCLUSIONS: COX-2, in part through TNF-alpha-related mechanisms, contributes to LPS-induced neuronal death. The data support the hypothesis that COX-2, in addition to its role in glutamate excitotoxicity, participates in the cytotoxicity associated with inflammation.

Animals↗
PubMed2001

Seizure's outcome after cortical resections including the face and tongue rolandic areas in patients with refractory epilepsy and normal MRI submitted to subdural grids' implantation.

PURPOSE: To study the seizure's outcome in patients with refractory epilepsy and normal MRI submitted to resections including the rolandic cortex. METHODS: Four adult patients were studied. All patients had motor or somatosensory simple partial seizures and normal MRI and were submitted to subdural grids' implantation with extensive coverage of the cortical convexity (1 in the non-dominant and 3 in the dominant hemisphere). RESULTS: ECoG was able to define focal areas of seizures' onset in every patient. All patients were submitted to resection of the face and tongue motor and sensitive cortex; two patients had resections including the perirolandic cortex and 2 had additional cortical removals. Three patients are seizures' free and one had a greater then 90% reduction in seizure frequency. CONCLUSION: Resections including the face and tongue rolandic cortex can be safely performed even within the dominant hemisphere.

Adult↗
PubMed2000

Cytosolic Ca2+ homeostasis is a constitutive function of the V-ATPase in Saccharomyces cerevisiae.

The vacuole is the major site of intracellular Ca(2+) storage in yeast and functions to maintain cytosolic Ca(2+) levels within a narrow physiological range via a Ca(2+) pump (Pmc1p) and a H(+)/Ca(2+) antiporter (Vcx1p) driven by the vacuolar H(+)-ATPase (V-ATPase). We examined the function of the V-ATPase in cytosolic Ca(2+) homeostasis by comparing responses to a brief Ca(2+) challenge of a V-ATPase mutant (vma2Delta) and wild-type cells treated with the V-ATPase inhibitor concanamycin A. The kinetics of the Ca(2+) response were determined using transgenic aequorin as an in vivo cytosolic Ca(2+) reporter system. In wild-type cells, the V-ATPase-driven Vcx1p was chiefly responsible for restoring cytosolic Ca(2+) concentrations after a brief pulse. In cells lacking V-ATPase activity, brief exposure to elevated Ca(2+) compromised viability, even when there was little change in the final cytosolic Ca(2+) concentration. vma2Delta cells were more efficient at restoring cytosolic [Ca(2+)] after a pulse than concanamycin-treated wild-type cells, suggesting long term loss of V-ATPase triggers compensatory mechanisms. This compensation was dependent on calcineurin, and was mediated primarily by Pmc1p.

Anti-Bacterial Agents↗