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C Hock

Publications and source records attributed to C Hock.

66 records · Page 4Linked to original sources
PubMed1992

Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism.

Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer: Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well established that the forebrain cholinergic system, whose integrity is essential for learning and memory functions, depends on the target-derived retrograde messenger nerve growth factor (NGF). Therefore, we measured NGF and choline acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in adult rats that had received a single injection of either STZ or artificial cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One week after ICV STZ treatment, NGF content was significantly decreased (-32%) in the septal region, where NGF-responsive cell bodies are located and NGF exerts its neurotrophic action after retrograde transport from NGF-producing targets. In contrast, NGF levels in the cortex and hippocampus, which are target regions for the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations in NGF levels were not related to changes in ChAT activity that decreased in the hippocampus by only 15%. This might be due to masking effects exerted by compensatory NGF-mediated stimulation of ChAT activity in remaining functional neurons. It is suggested that impaired behavior which has been observed after STZ-induced impairment of cerebral glucose and energy metabolism may be at least partially related to a diminished capacity of central NGF-responsive neurons to bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation.

After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45-65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF-transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time.

Animals↗
PubMed1990

Nerve growth factor levels and choline acetyltransferase activity in the brain of aged rats with spatial memory impairments.

Nerve growth factor (NGF) and choline acetyltransferase (ChAT) activity levels were measured in 7 different brain regions in young (3-month-old) and aged (2-years-old) female Sprague-Dawley rats. Prior to analysis the spatial learning ability of the aged rats was assessed in the Morris' water maze test. In the aged rats a significant, 15-30%, increase in NGF levels was observed in 4 regions (septum, cortex, olfactory bulb and cerebellum), whereas the levels in hippocampus, striatum and the brainstem were similar to those of the young rats. The NGF changes did not correlate with the behavioral performance within the aged group. Minor 15-30%, changes in ChAT activity were observed in striatum, brainstem and cerebellum, but these changes did not correlate with the changes in NGF levels in any region. The results indicate that brain NGF levels are maintained at normal or supranormal levels in rats with severe learning and memory impairments. The results, therefore, do not support the view that the marked atrophy and cell loss in the forebrain cholinergic system that is known to occur in the behaviorally impaired aged rats is caused by a reduced availability of NGF in the cholinergic target areas. The results also indicate that the slightly increased levels of NGF are not sufficient to prevent the age-dependent atrophy of cholinergic neurons, although they might be important for the stimulation of compensatory functional changes in a situation where the system is undergoing progressive degeneration.

Aging↗
PubMedDate not supplied

The PHA-induced calcium signal in lymphocytes is altered after blockade of K(+)-channels in Alzheimer's disease.

Several lines of evidence indicate that alterations in intracellular calcium homeostasis with sustained elevation of free calcium ions ([Ca2+]i) might be important in the pathophysiology of Alzheimer's disease (AD). Recent studies with peripheral blood-cells have demonstrated that investigation of regulatory mechanisms in calcium homeostasis might be more promising than determining only resting or stimulated [Ca2+]i values. With respect to the importance of potassium (K+)-channels in intracellular calcium regulation we have investigated whether a potassium channel dysfunction, already demonstrated for AD fibroblasts (Etcheberrigaray et al., 1993, Proceedings of National Academy of Sciences USA, 90, 8209-8213), could be observed in circulating lymphocytes as well. Thus, we studied the influence of the K(+)-channel inhibitor tetraethylammonium (TEA) on basal and PHA-stimulated [Ca2+]i in lymphocytes from AD (n = 20), non-demented depressed patients (n = 15) and age-related healthy controls (n = 23). Preincubation of lymphocytes with 100 mmol/l TEA resulted in a 45.5 +/- 8.8% inhibition (mean +/- SD) of the PHA induced rise in [Ca2+]i in healthy controls and 37.3 +/- 11.3% inhibition in depressed patients. With lymphocytes of AD patients, this effect of TEA was significantly reduced (23.2 +/- 8.8%, p < .001). If the individual data are considered there was almost no overlap between AD patients and healthy controls, since only three (15%) AD patients responded to TEA with > 30% inhibition, but only one of the controls (5%) responded with < 30% inhibition. Besides the reduced signal-inhibition by blockade of K(+)-channels we have observed a delayed response of AD lymphocytes in [Ca2+]i rise after PHA stimulation, suggesting that functional plasticity of the cells is reduced. Although the significance and molecular basis of this K(+)-channel dysfunction are not yet determined, the presented data are of great significance because of diagnostic reasons and especially because this model thus offers a possibility to investigate functional cellular alterations in vivo.

Adult↗
PubMedDate not supplied

Interactive computer-based cognitive training in patients with Alzheimer's disease.

The present paper presents data from ten patients suffering from mild to moderate Alzheimer's disease (AD), all of whom were trained to use an interactive computer-based program. Using photographs of the patient and his or her personal surroundings, an everyday task of relevance to the patient was simulated on a PC-touch screen, which the patient was trained to operate. After three weeks of training (three to four sessions a week), the patients needed less help in performing the programs, they became faster, and eight out of ten made fewer mistakes. The results were most pronounced in patients with a poor performance at the beginning, and there was no difference between early-onset (EO) and late-onset (LO) AD patients. Although the training was generally well received, there was no evidence of a general cognitive improvement, and it remains an open question whether the results achieved with PC training can be transferred to real-life situations.

Activities of Daily Living↗
PubMedDate not supplied

Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer's dementia.

We investigated the immunohistochemical alterations of angiotensin converting enzyme (ACE), angiotensin II and AT1 receptor in the parietal cortex in Alzheimer's dementia (AD) to reveal the contributive role of the brain renin-angiotensin system in the disease process. In controls, ACE, angiotensin II and AT1 immunoreactivities were localized to pyramidal neurons of the cortex. The staining intensity was distinctly increased in AD for all three antigens, involving predominantly cortical layer V, which may reflect the enhanced brain renin-angiotensin system activity in the disease process. In addition, a prominent perivascular ACE and angiotensin II immunoreactivity surrounding some cortical vessels in aged controls and AD patients points to an underlying microvascular pathology in the process of neurodegeneration.

Aged↗
PubMedDate not supplied

Genetics of interleukin 6: implications for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that preferentially affects individuals above 60 years, with increasing risk in older ages. Neuropathological hallmarks of AD include brain atrophy, senile plaques, and neurofibrillary tangles. In addition, inflammatory processes frequently accompany the neuropathology of AD. Among several mediators of the inflammatory response, interleukin 6 (IL6) may play a role in these inflammatory processes. Polymorphisms of the IL6 gene are associated with changed IL6 gene expression, and with altered immune responses resulting in such phenotypes as early transplant rejection, the development of anti-histone antibodies in systemic lupus erythematosus, or altered bone resorption in osteoporosis. Recent data suggested that IL6 is also genetically associated with AD, but many questions remain to be answered. Which polymorphic sites can be identified within functional regions of IL6, and how do they affect gene expression, neurobiological function and pathophysiological events in health and AD? Are there interactions of other genes with IL6 that affect the development and progression of AD? Are such interactions additive, sub-additive, synergistic, or epistatic in nature? How do IL6 polymorphisms influence the therapy of AD? Answering some of these questions will be a good start toward assessing the role of IL6 in the genetics of AD.

Alzheimer Disease↗
PubMedDate not supplied

Evidence of blood-cerebrospinal fluid-barrier impairment in a subgroup of patients with dementia of the Alzheimer type and major depression: a possible indicator for immunoactivation.

Serum and cerebrospinal fluid (CSF) from 44 patients with clinical probable Alzheimer's disease (AD) (subdivided in two groups with 18 early onset, EO, and 26 late onset, LO, cases), 10 patients with vascular dementia (VD) and 24 patients with major depression (MD) were assayed for concentrations of albumin and IgG. The severity of dementia was assessed with the Mini Mental State Examination. The CSF/serum ratio for albumin and IgG as well as the IgG index were used to evaluate blood-CSF barrier function. Various patients showed signs of blood-CSF-barrier (BCB) dysfunction and only few displayed evidence of local IgG synthesis in the central nervous system (CNS) in the AD, VD and in the MD group (IgG index > 0.7). The permeability of the blood-CSF barrier was not correlated to measures of dementia severity. Our data support the hypothesis of a BCB leakage in a subgroup of all investigated patients. Furthermore, we found a small number of patients with increased intrathecal IgG synthesis. Elevated CSF immunoglobulins combined with BCB impairment might be associated or caused by a general immune activation. Our data are in agreement with the assumption that an inflammatory process may play a role in a subgroup of patients with AD but also with MD and less likely in VD. In conclusion BCB impairment and elevated IgG immunoglobulin levels are unspecific either for AD, VD or MD.

Aged↗
PubMedDate not supplied

A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease.

This 12-week, multinational study compared the tolerability and cognitive effects of donepezil (up to 10 mg once daily) and rivastigmine (up to 6 mg twice daily) in 111 patients with mild to moderate Alzheimer's disease. Both medications were administered open label according to recommended dosing regimens from the respective product labelling available during the conduct of the study. More patients in the donepezil group (89.3%) completed the study compared with the rivastigmine group (69.1%; p=0.009), and 10.7% of the donepezil group and 21.8% of the rivastigmine group discontinued due to adverse events (AEs); 87.5% of donepezil-treated patients and 47.3% of rivastigmine-treated patients remained on the maximum approved dose of each drug at the last study visit. Both groups showed comparable improvements on the ADAS-cog administered by raters blind to study medication at weeks 4 and 12. Thus, using the recommended dosing schedules, donepezil was better tolerated with fewer discontinuations due to AEs, and both agents improved cognition to a similar extent.

Aged↗
PubMedDate not supplied

The technique of obtaining pancreatic segments in dogs: surgical-anatomical aspects.

The technique of obtaining pancreatic segments was studied in 60 mongrel dogs by removing the right pancreatic lobe. At the same time comparative surgical-anatomical examinations were performed for the detection of the vascular variations of the right pancreatic segment. In 83% of the cases the arterious and venous systems were suitable for gaining grafts (Types I-II). In 12% the segment was suitable for grafting only if the venous network had an optimal course (Type III), while in 5% the segment was unsuitable because it did not have a suturable arterial stump (Type IV).

Animals↗
PubMedDate not supplied

[Quantification of dementia-related disabilities in daily behavior with the DAFS (Direct Assessment of Functional Status): reliability and validity of a German test version].

The DAFS (Direct Assessment of Functional Status) is a new test for the assessment of competence of demented patients in situations of everyday life. The present study assesses objectivity, temporal stability, concurrent and discriminative validity of a German version of the DAFS. Sixteen patients with a DSM-III-R-diagnosis of dementia of the Alzheimer's type, 8 of which with a mild (MMSE 18-25) and 8 with a moderate (MMSE 12-17) dementia, and 8 control subjects without any symptoms of dementia (MMSE 28-30), matched with the patient groups in age, gender and education, were assessed three times within 3 weeks with the DAFS and once with the NOSGER (an ADL rating scale). The DAFS showed high objectivity (correlation between two test administrators r = .97) and stability (2 week retest reliability r = .98) and was able to discriminate significantly between the study groups and with a strong effect size. Correlations with the total score and the IADL subscale score of the NOSGER were high (r = .81 and r = .86, resp.), whereas correlations with the mood and the disturbing behavior subscale were much lower (both r = .54). This investigation could demonstrate that the DAFS is an objective, stable and valid test instrument. It has a high power to discriminate between demented and non-demented subjects as well as between various degrees of severity of illness. The test items are highly relevant for everyday functioning and the test itself is a good and necessary addition to the use of ADL or IADL rating scales.

Activities of Daily Living↗