[Premature immunosenescence: a pathogenetic factor in Alzheimer's disease?]. / Vorzeitige Immunalterung: ein pathogenetischer Faktor bei Alzheimer-Demenz?

While the familial form of Alzheimer's disease (AD) is known to be entirely inherited, the etiopathogenesis of the most common late-onset form of Alzheimer's disease still remains unresolved. Among various factors, aging seems to be one of the most prominent risk factors. Moreover, a large body of evidence points to the contribution of immunological alterations in AD. The involvement of inflammatory factors in the etiopathology has been widely discussed. Moreover, an impairment of certain immune responses in AD has been observed. Presumably, premature immunosenescence may lead to inadequate immune reactions. Against this background, the development of different immunotherapeutic strategies seems to be a promising challenge for future research.

[The L-DOPA-propranolol test for the evaluation of reserves in secretory growth hormone]. / Der L-Dopa-Propranolol-Test zur Uberprüfung der sekretorischen Wachstumshormonreserve.

The growth hormone (GH) reserve of 75 short probands (age 1.9 to 23.8 years) was evaluated on the basis of oral L-dopa (300 mg/m2) and propranolol (0.75 mg/kg) administration. The GH response was normal in 21 probands (20.9 +/- 1.24 ng/ml; means +/- SEM) and was found to be higher than the response to the insulin or arginine test. 39 patients failed to respond (less than 6 ng/ml) and were diagnosed as GH deficient. In 15 cases an "intermediate" response (greater than 6 less than 12 ng/ml) was found and in these patients partial GH deficiency was assumed. There was not a single false positive result with this test, which cannot be said for any of the other commonly-used stimulation tests. In two children hypoglycaemic blood glucose levels were observed during the test, whilst in one case loss of consciousness and convulsions were seen. In four patients the test had to be interrupted because of side effects. These children had the following findings in common: GH deficiency was confirmed and the patients were still very young and basal blood glucose levels were relatively low at the beginning of the test. The L-dopa-propranolol test is an effective and reliable GH stimulation test, but severe side effects may occur.

[Effect of intranasal administration of an LH-RH analog on basal gonadotropin concentrations and stimulation in patients with hypogonadotropic hypogonadism]. / Einfluss eines pernasal angewandten LH-RH-Analogons auf basale Gonadotropinkonzentrationen sowie deren Stimulierbarkeit bei Patienten mit hypogonadotropem Hypogonadismus.

The effect of intranasal administration of the LHRH analogue D-Leu-6-des Gly-10 NH2EA on gonadotropin (Gn) stimulation was studied in 8 juvenile patients with ascertained hypogonadotropic hypogonadism, due to multiple pituitary deficiencies (MPD) in 5 cases and the Prader-Willi syndrome (PWS) in the remaining 3 patients. A bolus LHRH test was performed before and after a treatment period lasting between 2 and 5 weeks. In 2 MPD patients there was a transient rise in basal LH concentrations and a slight improvement in the second LHRH test; hence a hypothalamic lesion is assumed. In the other MPD patients there was no change in Gn stimulation. The sex steroid levels remained low. Gn stimulation was improved in all 3 patients with PWS after LHRH administration and in one 19-year-old boy the onset of puberty was probably induced by this therapy. However, after continuous administration of the analogue the initially increased Gn levels decreased again. In view of this inhibiting action on Gn levels the LHRH analogue does not appear suitable for the long-term treatment of hypogonadotropic hypogonadism.

Macrophage colony-stimulating factor (M-CSF) in plasma and CSF of patients with mild cognitive impairment and Alzheimer's disease.

Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that activates microglial cells, involved in phagocytosis of amyloid-beta (Abeta) in the brain. In the present study, we found in 50 patients with Alzheimer's disease (AD) significantly increased M-CSF plasma levels compared to 22 patients with mild cognitive impairment (MCI) and 35 age-matched healthy controls. In contrast, MCI patients showed significantly decreased M-CSF levels in cerebrospinal fluid (CSF) compared to AD patients and 20 patients with other non-inflammatory neurological disease (NIND). Analyzing the impact of Beta-amyloid 1-42 (Abeta 1-42), tau protein and M-CSF for differentiation between the groups we found that M-CSF, but not Abeta 1-42 and tau-protein is a significant parameter for distinction between MCI and NIND patients with 68.8% sensitivity and 75.0% specificity. M-CSF CSF levels < or = 357.8 pg/ml yielded 73.7% sensitivity and 75.0% specificity for diagnosing MCI patients in comparison with control subjects. In conclusion, our data indicate that M-CSF in CSF could be a putative biomarker for MCI.

Stage-dependent BDNF serum concentrations in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores >or=21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3). As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls.In summary, BDNF serum values are increased in early stages of Alzheimer's disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer's disease.

LeProT1, a transporter for proline, glycine betaine, and gamma-amino butyric acid in tomato pollen.

During maturation, pollen undergoes a period of dehydration accompanied by the accumulation of compatible solutes. Solute import across the pollen plasma membrane, which occurs via proteinaceous transporters, is required to support pollen development and also for subsequent germination and pollen tube growth. Analysis of the free amino acid composition of various tissues in tomato revealed that the proline content in flowers was 60 times higher than in any other organ analyzed. Within the floral organs, proline was confined predominantly to pollen, where it represented >70% of total free amino acids. Uptake experiments demonstrated that mature as well as germinated pollen rapidly take up proline. To identify proline transporters in tomato pollen, we isolated genes homologous to Arabidopsis proline transporters. LeProT1 was specifically expressed both in mature and germinating pollen, as demonstrated by RNA in situ hybridization. Expression in a yeast mutant demonstrated that LeProT1 transports proline and gamma-amino butyric acid with low affinity and glycine betaine with high affinity. Direct uptake and competition studies demonstrate that LeProT1 constitutes a general transporter for compatible solutes.