Quercetin in equine frozen semen.

　　BACKGROUND: Supplementation of sperm diluents to reduce the damage caused by the freeze-thaw cycle is broadly used in equine semen cryopreservation. OBJECTIVE: The present study aimed at determining the most appropriate quercetin supplementation in equine freezing extender. MATERIALS AND METHODS: Quercetin at four different concentrations (0.25, 0.5, 0.75 or 1 mM) was added in the sperm freezing diluent before the freeze-thaw cycle. The spermatozoa population was analyzed by flow cytometry and a statistical analysis was conducted to detect significant differences between control and treated samples. RESULTS: The statistical analysis did not reveal any significant modification of seminal parameters. CONCLUSION: Within the concentrations tested, quercetin supplementation in equine freezing extender did not affect progressive motility, mitochondrial functionality, acrosome reaction, membrane integrity or DNA fragmentation index in post-thaw equine semen.

[Screening for dementia using telephone interviews. An evaluation and reliability study of the Telephone Interview for Cognitive Status (TICS) in its modified German version]. / Demenzscreening per Telefon. Eine Reliabilitäts- und Evaluationsstudie zum Telefoninterview für den kognitiven Status (TICS) in seiner modifizierten deutschen Fassung.

BACKGROUND: To assess cognitive impairment or dementia in epidemiologic studies using telephone interviews for data acquisition, valid, reliable and short instruments suitable for telephone administration are required. For the Telephone Interview for Cognitive Status (TICS) in its modified German version, the only instrument used in Germany so far, more data on reliability and practicability are needed. MATERIAL AND METHODS: Participants were recruited in the offices of nine primary care physicians. Data from 197 participants (115 females, mean age 78.5±4.1 years) who were tested by telephone and in the office by means of the Mini-Mental State Examination (MMSE) were used for the evaluation. For assessing reliability, a group of 91 participants (55 females, mean age 78.1±4.1 years) was contacted twice during 30 days to be tested during a telephone interview by means of the TICS in its modified German version. RESULTS: The intraclass correlation coefficient (ICC), a measure of reliability, was 0.67 [95% confidence interval (CI): 0.53; 0.77]. The Bland-Altman plot did not reveal any relationship between the variability of the difference between repeated measures and the total amount of the measure. For the overall TICS score, no differences were found between repeated measurements. However, the tasks recall of the word list and counting backwards showed some improvement in the repeated tests. TICS and MMSE showed only moderate correlation, with a correlation coefficient of 0.48 (95% CI: 0.36; 0.58). TICS values were dependent on age and educational level of the person tested. CONCLUSIONS: The TICS in its modified German version appears to be of acceptable reliability for the assessment of cognitive impairment during a telephone interview. TICS values depend on age and educational level of the person tested. TICS and MMSE correlate only moderately.

[Prerequisites for a new health care model for elderly people with multiple morbidities: results and conclusions from 3 years of research in the PRISCUS consortium]. / Voraussetzungen für ein neues Versorgungsmodell für ältere Menschen mit Multimorbidität: Ergebnisse und Schlussfolgerungen aus 3-jähriger Forschung im PRISCUS-Verbund.

BACKGROUND: The concurrent presence or manifestation of multiple chronic conditions, i.e. multimorbidity, poses a challenge to affected patients and their relatives, physicians, and practitioners, and to the health care system in general. Aiming to improve medical care for different chronic diseases, the Chronic Care Model also appears to be suited for multimorbidity. The established research consortium PRISCUS is trying to create some of the prerequisites for a new care model for multimorbid, elderly patients oriented along the lines of the Chronic Care Model. METHODS AND RESULTS: Four out of seven subprojects of the research consortium provide an overview of some of their findings. Topics in a sports medicine subproject were the assessment of physical activity by means of a newly developed questionnaire and the development and feasibility testing of an exercise program for elderly people with chronic conditions and mobility impairment. Partners from family medicine implemented geriatric assessment in a primary care setting and evaluated its consequences. In a pharmacological subproject, potentially inappropriate medication as well as drug-drug interactions and dosing errors were addressed. The health economic subproject investigated quality of life impairment due to multiple chronic diseases and the effects of multimorbidity on costs. CONCLUSIONS: The results of the PRISCUS research consortium allow a better description of consequences of multimorbidity and illustrate at least some new approaches towards prevention, diagnosis, and treatment of patients suffering from multimorbidity. Ongoing projects will test the efficacy of a physical activity program and a new complex intervention to reduce potentially inappropriate medication in the elderly. With this, the research consortium will create some prerequisites for a new health care model for patients with multimorbidity comparable to the Chronic Care Model.

[Influence of extreme weather conditions on the deployment volume of emergency medical services]. / Einfluss von Wetterextrema auf Einsatzzahlen im Notarztdienst.

BACKGROUND: Due to global warming a worldwide increase in the frequency and intensity of heat waves have been forecast. In the context of the overall increasing number of emergency service calls, weather-induced effects on the number of calls are highly relevant. We evaluated the influence of extreme temperatures on emergency medical services. MATERIALS AND METHODS: The study was conducted in Bochum, Germany. The authors examined the data from 16,767 emergency calls. In addition, the daily updated temperature data were collected for each emergency doctor call. Data were collected from 01 January 2014 until 31 December 2015. The primary question was the influence of extremes of the perceived temperature (PT; on the day of the call and the three previous days) on the diagnosis group of cardiovascular diseases. A secondary question was the influence of extremes of the temperature parameters (air temperature, PT, physiological equivalent temperature [PET]) on the day of call and the three previous days. RESULTS: A total of 16,767 calls were assessed. The threshold values (upper and lower 5%) were -8.7 and 32.5 °C for PT and -0.7 and 26.7 °C for air temperature. Examination of the PT indicated a significantly increased rate of calls for cold spells on the day of the call (RR = 1.14; p = 0.033) as well as a lag effect of 3 days (RR = 1.1; p = 0.049). CONCLUSION: The present study shows that during cold spells there is an increased rate of calls for cardiovascular diseases. This effect is not only observable on the extreme day itself but also 3 days later.

Scanning force microscopy studies of the colonization and growth of A. ferrooxidans on the surface of pyrite minerals.

We have used the technique of scanning force microscopy (SFM) for studying the interaction of the bacteria A. ferrooxidans with the surface of the mineral pyrite. These bacteria are important to study with regard to acidification of streams and the environmental impact of such acidification. A. ferrooxidans cells readily colonize the pyrite surface, forming a tight mineral seal between the cell and the pyrite substrate. These bacteria subsequently may grow under pH neutral conditions, biooxidizing the underlying pyrite; this process creates etch pits in the pyrite. On average, these etch pits are 1.2 microns in lateral dimension and approximately 220 nm deep.

Analysis of human hemopoietic progenitor cells for the expression of glycoprotein IIIa.

Human hemopoietic progenitor cells were examined for the expression of glycoprotein IIIa (GPIIIa). This protein, which forms the beta-subunit of the GPIIb/IIIa receptor for cytoadhesive proteins as well as the beta-subunit of the vitronectin receptor, represents the most sensitive cell surface marker so far identified for the megakaryocytic lineage. Bone marrow cells were fractionated by a discontinuous Percoll gradient to separate cells that form megakaryocytic colonies in culture (1.05 greater than rho less than 1.077 g/ml). Density centrifugation was followed by indirect immunopanning to select for an enriched population of progenitor cells depleted of most of the mature cells of the myeloid, lymphoid, and erythroid lineages. This cell suspension was labeled with antibodies directed against determinants of GPIIIa and analyzed using a fluorescence-activated cell sorter (FACS). Fractions of cells were sorted and analyzed for the ability to form hemopoietic colonies in culture. Our study demonstrated that megakaryocytic progenitor cells (CFU-M) as well as granulocyte-macrophage colony-forming units (CFU-C), erythroid colony-forming units (BFU-E), and mixed lineage colony-forming units (CFU-GEMM) express HLA-DR antigens but lack GPIIIa. Therefore GPIIIa represents a marker that is not present on hemopoietic progenitor cells, but is expressed on the progenies of CFU-M. In view of the importance of GPIIIa as a component of receptors for cytoadhesive proteins, this finding may help to elucidate the adhesive interactions between early hemopoietic cells and bone marrow interstitium.

Detection of messenger RNAs within single hemopoietic cells by in situ hybridization on small slide areas.

In situ hybridization provides a powerful tool to detect specific mRNA sequences at the cellular level. We have applied a modified in situ hybridization technique using specifically prepared regular glass microscope slides to evaluate mRNA levels in cells of small samples. Cells were derived from in vitro colonies or isolated by fluorescence-activated cell sorting and deposited on the slides. These slides were coated with polysiloxane, sparing small circular areas where adherent cells attach and can be grown directly; after preincubation of the collection areas with fibronectin, the slides can also be used to deposit and to grow nonadherent cells. In situ hybridization was performed with 35S-labeled probes. Acetylation of the slides and the cells prior to hybridization, the addition of vanadyl-ribonucleoside complexes, and a prehybridization step were found to be necessary to optimize signal-to-noise ratios, as shown by evaluation of c-myc-specific mRNA in phytohemagglutinin-stimulated T4-lymphocytes. This technique might be very useful to study mRNA expression in small samples of hemopoietic cells.

Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type.

The effect of age on regional cerebral metabolic rate of glucose (rCMRGl) was studied in 14 patients with presenile dementia of Alzheimer type (DAT) and 24 patients suffering from senile DAT in comparison to 20 age-matched normal subjects by positron emission tomography (PET) of 2-(18F)-fluoro-2-deoxy-D-glucose (FDG). The metabolic pattern was condensed to a single metabolic ratio. It was calculated as the quotient of rCMRGl in regions typically affected by AD (frontal and temporoparietal cortex) divided by that in regions typically not affected. In normals this ratio was 1.05 +/- 0.04 and did not depend on age. In patients, the metabolic ratio was generally smaller and there was a significant difference between presenile (0.82 +/- 0.1) and senile DAT (0.90 +/- 0.1). This was due to a different metabolic pattern in the two age groups: metabolic impairment was focused on frontal and temporo-parietal cortex in presenile DAT, whereas more global rCMRGl reductions were present in senile DAT. The results suggest a more generalized disorder in senile dementia impairing metabolism globally in addition to the more localized changes that are typical for DAT.

Severity of vascular dementia is related to volume of metabolically impaired tissue.

The relation between dementia severity and regional cerebral metabolic rate of glucose was studied in 28 patients with vascular dementia (VD) in comparison with 20 age-matched patients who were suffering from Alzheimer's disease (AD) and 24 normal subjects by using positron emission tomography with fludeoxyglucose F 18. Similar metabolic impairment was found in the temporoparietal and frontal association cortex in patients with VD and in those with AD. Metabolism of the basal ganglia, thalamus, and cerebellum was reduced significantly in patients with VD only. The total volume of regions with metabolism below the 95% confidence interval of control values was significantly related to the severity of dementia but did not differ between patients with VD and those with AD. A metabolic ratio of regional cerebral glucose metabolism of association areas divided by regional cerebral glucose metabolism of structures that were typically not affected by AD was significantly lower in patients with AD than in those with VD. This ratio was also related to dementia severity in both types of dementia.

An interactive technique for three-dimensional image registration: validation for PET, SPECT, MRI and CT brain studies.

UNLABELLED: A multipurpose three-dimensional registration technique was validated with PET, SPECT, CT and MRI scans, which had been obtained under normal clinical conditions. In contrast to fully automated procedures, this coregistration method is highly interactive, which has the advantage that it does not impose rigid restrictions by data type and by alterations in normal anatomy or brain function resulting from disease. METHODS: Basically, a computer program provides a variety of tools to examine the accuracy of coregistration visually and to specify necessary translations and rotations in all three dimensions. Tools and criteria to accept coregistration were applied according to a standardized protocol. Reproducibility was assessed with five independent users on nine pairs of image sets. In two pairs of these image sets, coregistration was repeated three times by each user. RESULTS: Depending on the resolution of the images involved, the reproducibility of translation distances ranged from 0.32 to 2.22 mm (s.d.) and of rotation angles from 0.32 to 1.70 degrees. It was always much smaller than the point-spread full-width half maximum of the device with the lower resolution. The accuracy of coregistration was examined using two arbitrarily misplaced image sets. Interindividual and intraindividual variance were similar, which suggested that the influence of subjectivity was not significant. Average displacements after coregistration were 0.43 and 0.29 mm or less for PET and MRI data, respectively, which indicated the absence of a systematic bias. CONCLUSION: The results indicate the high reproducibility and accuracy of this three-dimensional coregistration technique, which is comparable or superior to those of automated techniques and methods based on external artificial landmarks.

Visual versus auditory memory stimulation in patients with probable Alzheimer's disease. A PET study with 18 FDG.

Patients with probable Alzheimer's disease were either stimulated with a continuous visual recognition task (n = 18) or with a continuous auditory recognition task during PET measurement with 18 FDG. The PET scanner was a Siemens CTI, ECAT EXACT with 5 mm transaxial and 6 mm axial resolution. The global stimulation effects were nearly identical in both groups and increased of 4.17 +/- 8.14% in the auditory stimulated group and of 4.03 +/- 11.78% in the visual stimulated group. Beyond regional stimulation effects in both groups a common cerebellar stimulation effect was measured. It is concluded that the cerebellar stimulation effect reflects a modality independent cognitive process and that the only small enhancement of global glucose metabolism indicates disturbed stimuli processes and finally explained the patient's failure in memory tasks.

Activation PET as an instrument to determine therapeutic efficacy in Alzheimer's disease.

Forty patients with probable Alzheimer's disease (AD) were selected from a pool of 80 patients and assigned to 4 groups. Each received either social support, cognitive training only, or cognitive training in combination with pyritinol or phosphatidylserine. Treatment duration was 6 months. Before and after treatment the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography (PET) and 2[18F]-fluoro-2-deoxy-D-glucose (FDG). Before treatment, the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task. They did not differ in scores of a neuropsychological test battery. After the treatment period the group with cognitive training + phosphatidylserine showed a significant glucose enhancement during the stimulation tasks in various brain regions, and an improvement in cognitive functioning compared to the other groups. The group with cognitive training + pyritinol had better stimulation effect as that of the social support group indicating that a combination of cognitive training + pharmacological intervention was superior than that of cognitive training alone.

EEG power changes are related to regional cerebral glucose metabolism in vascular dementia.

OBJECTIVE: In patients with vascular dementia (VD), the relationship between the EEG power within the 4 frequency bands and the regional metabolic disturbances was investigated. METHODS: Twenty-eight patients (age 69.0+/-6.54 years) with VD according to NINDS-AIREN criteria underwent quantitative EEG recording, according to the 10-20 system, and fluodeoxyglucose F18 positron emission tomography (PET) at resting condition within 24 h. EEG power FFT-analysis was performed for delta (2-3.5 Hz), theta (4-7.5 Hz), alpha (8-13 Hz) and beta (13.5-20 Hz) frequency bands. Regional EEG power bands were related to regional glucose metabolism in anatomically defined regions corresponding to locations of the 10-20 system. RESULTS: Correlation between slow frequency band power and glucose metabolism was found. A widespread inverse relationship of delta power to metabolism was found between various regions; additionally, delta power was negatively correlated to cerebral glucose metabolism in individual regions. Frontal theta power correlated especially with thalamic CMRglc. Alpha power correlated directly with metabolism in the occipital lobe. No significant relationships were found between beta power and metabolism. CONCLUSION: We conclude that EEG power in VD is linked to glucose metabolism, indicating specific regional dependencies.

Apolipoprotein E polymorphism influences the cerebral metabolic pattern in Alzheimer's disease.

In 49 patients with the clinical diagnosis of probable Alzheimer's disease (AD) apoE genotyping as well as regional cerebral glucose metabolism (rCMRGI) using positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) were studied. The metabolic pattern was condensed to a ratio by dividing the rCMRGI of typically affected regions (temporo-parietal and frontal association cortex) by the rCMRGI of the least affected regions (primary cortical areas, basal ganglia, cerebellum and brainstem). Epsilon4-heterozygotes and epsilon4-homozygotes were grouped together, and also those lacking the epsilon4-allele (non-epsilon4). For the metabolic pattern we found a significant correlation to severity of dementia in both groups (epsilon4: r = 0.49, P = 0.05; non-epsilon4: r = 0.59, P = 0.006). On ANCOVA severity of dementia and epsilon4 status were independent predictors of the cerebral metabolic pattern (P = 0.01). These differences may be attributed to epsilon4 dependent histopathologic changes.

P300 in Alzheimer's disease: relationships to dementia severity and glucose metabolism.

In 45 patients (aged 48-85 years) with probable Alzheimer's disease (AD) according to current research criteria (NINCDS-ADRDA) with different stages of dementia severity (Mini Mental Status Examination (MMSE) 7-27) the auditory evoked P300 waves were mapped and regional cerebral metabolic rates of glucose were measured by positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose. Age adjusted P300 latency was significantly correlated to dementia severity (r = -0.33, p = 0.028), but no significant relationships were found for P300 amplitudes. Dependencies existed among cortical glucose metabolic rates and MMSE with the highest correlation coefficient for the metabolic ratio of regions typically affected and non-affected in AD (r = 0.75, p = 0.0001). A significant correlation was also calculated between P300 latency and metabolic ratio (r = -0.44, p = 0.002), but no relationships were observed among P300 amplitudes and glucose metabolic rates of individual brain regions. These results indicate that P300 latency and metabolic rates but not P300 amplitudes qualify as measures of severity in AD. The lack of regional correlations among P300 amplitudes and glucose metabolism is not consistent with a cortical contribution to P300 generation.

Propentofylline enhances cerebral metabolic response to auditory memory stimulation in Alzheimer's disease.

To evaluate efficacy, safety, metabolic and clinical effects of propentofylline in Alzheimer's disease (AD), a prospective, randomized, double-blind, placebo-controlled trial was performed in 30 patients with mild to moderate AD who underwent pretreatment and posttreatment 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography under resting conditions and during stimulation with an auditory memory paradigm. Twenty-eight subjects completed the 3-month study. The drug was well tolerated. In the active treatment group, a significant increase of cerebral metabolic response to the memory task was observed (multiple measurement ANOVA P = 0.02). The placebo group showed a significantly decline in the MMSE score (P = 0.02) while there was no change in the treatment group. This suggests a protective role for propentofylline in slowing the progression of AD.

Difference of regional cerebral metabolic pattern between presenile and senile dementia of the Alzheimer type: a factor analytic study.

Positron emission tomographic studies using metabolic ratios to represent the contrast between certain brain regions have shown differences of cerebral glucose metabolism between presenile and senile dementia of Alzheimer type (DAT). In this study, factors for regional variance of cerebral metabolism in 61 patients with probable Alzheimer's disease were obtained using principal component analysis (PCA). The difference between two age groups of DAT patients according to age at onset < or = 65 years (n = 30) and > 65 years (n = 31) were investigated. A PCA using nine pairs of cerebral regions normalized to cerebellum for reduction of intersubject variability identified five regional factors for cerebral metabolism: one each for the left and right temporo-parietal cortex, and the other three for frontal cortex, primary visual and sensorimotor cortex, and mesial temporal sensorimotor cortex, and mesial temporal cortex. The age groups differed significantly only in the factor for the right temporo-parietal cortex, with a more prominent metabolic reduction in presenile than senile DAT. Severity of dementia was correlated with the factors for the right and left temporo-parietal cortex. The effect of age at onset on glucose metabolism of the right temporo-parietal cortex was independent from that of dementia severity in DAT.

Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia.

In a double-blind, placebo-controlled trial in thirty patients with mild to moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of the adenosine uptake blocker propentofylline (HWA 285) on regional cerebral glucose metabolism (rCMRGl) was studied using positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). 25 subjects completed the 3-months study. Propentofylline significantly improved relative rCMRGl in the motor cortex, while relative rCMRGl in the placebo treated group worsened significantly. Neuropsychologically, visual information processing was improved in the propentofylline group and we observed a trend towards a slowing of the progression of cognitive deterioration in patients with VD. The results of the longitudinal analysis showed further that neuropsychological and metabolic changes are closely related. These findings justify a large-scale clinical trial to prove therapeutic efficacy.

Positron emission tomography for diagnosis of Alzheimer's disease and vascular dementia.

In mild or atypical cases of Alzheimer's disease (AD) the differential diagnosis to other dementing diseases, such as vascular dementia (VD), may pose a difficult problem. Beside computed tomography (CT) and magnetic resonance imaging (MRI), functional neuroimaging by positron emission tomography (PET) support the clinical diagnosis by visualizing cerebral function. PET of 18F-2-fluoro-2-deoxy-D-glucose (FDG) for measurement of regional cerebral glucose metabolism (rCMRGl) has shown a typical metabolic pattern in patients with probable AD: hypometabolism in temporoparietal and frontal association areas, but relative recessing of primary cortical areas, basal ganglia and cerebellum. In VD a different pattern is seen. It consists of scattered areas with reduction of rCMRGl typically extending over cortical and subcortical structures. Severity of dementia is correlated with rCMRGl reduction in the temporoparietal association cortex, irrespective of the cause of dementia. Also the total volume of hypometabolic regions is related to severity of dementia but did not differ between AD and VD, even in patients with small lacunar infarction. This indicates that the total volume of functional tissue loss is more important since it also includes the effects of incompletely infarcted tissue and morphologically intact but deafferented cortex. The characteristic metabolic pattern has a high diagnostic accuracy for the discrimination between probable AD, normals and VD, even in patients with mild cognitive impairment. Under clinical and therapeutic aspects the analysis of longitudinal changes of rCMRGl has shown that neuropsychological and metabolic changes are closely related in both, AD and VD.

Vascular dementia: perfusional and metabolic disturbances and effects of therapy.

Positron emission tomography (PET) has elucidated basic pathophysiological mechanism that produce the cognitive decline in vascular dementia (VD). The typical pattern of glucose metabolism seen in VD with scattered areas of focal cortical and subcortical hypometabolism differs from that in AD with marked hypometabolism affecting the association areas. The total volume of metabolically inactive tissue is significantly related to severity of dementia. Rather than the quantity of tissue destruction, the critical effect may be the quantity of cortical hypometabolism caused by subcortically induced disconnection. Studies with HMPAO SPECT have shown focal deficits in VD and AD patients that are comparable to those seen with FDG PET. In mildly demented patients performance for the classification AD versus VD is much better by PET because it might be more sensitive for imaging small functional pathological changes. A longitudinal analysis of rCMRGl in VD showed that the progression of dementia can be delayed by the adenosine uptake blocker propentofylline and that neuropsychological and metabolic changes are closely related.