Buchbesprechungen

Ohne Zusammenfassung     

Oligodynamische Metallwirkung und Hämolyse

Ohne ZusammenfassungAuszug aus einer Inaugural-Dissertation. Freiburg i. Br. 1924.     

Circulating adhesion molecules in allergic and non-allergic asthma

Circulating forms of adhesion molecules (intercellular-adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin ) are related to the turnover of these molecules on the cell surface. In contrast to the other molecules, the levels of E-selectin probably exclusively reflect the activity of endothelial cells. The aim of this study was to compare levels of circulating adhesion molecules in patients with allergic (AA) and non-allergic asthma (NA) and to relate the levels of soluble adhesion molecules to methacholine responsiveness and lung function. The study comprised 19 patients with AA, 15 patients with NA and 17 healthy subjects. Soluble adhesion molecules, spirometry, methacholine responsiveness and peak flow variability was measured. The group of patients with AA had higher levels of sE-selectin than the reference group (P=0.046). Serum levels of sE-selectin correlated significantly with bronchial responsiveness (r=0.76) and peak flow variability (r=0.75) (P<0.01) in the NA but not in the AA group. All adhesion molecules in AA (P<0.05-<0.001), but only sE-selectin in NA (P<0.05), were correlated to airway conductance. sVCAM-1 was reduced by inhaled steroids (P<0.01). Our results indicate that endothelial cells are activated in asthma and that this activity has a bearing on airflow variability and bronchial responsiveness in NA.     

The Mood Stabilizer Lithium Potentiates the Antidepressant-Like Effects and Ameliorates Oxidative Stress Induced by Acute Ketamine in a Mouse Model of Stress

Background:

Evidence suggests that mammalian target of rapamycin activation mediates ketamine’s rapid but transient antidepressant effects and that glycogen synthase kinase-3β inhibits this pathway. However, ketamine has associated psychotomimetic effects and a high risk of abuse. The mood stabilizer lithium is a glycogen synthase kinase-3 inhibitor with strong antisuicidal properties. Here, we used a mouse stress model to investigate whether adjunct lithium treatment would potentiate ketamine’s antidepressant-like effects.

Methods:

Mice received chronic restraint stress and long-term pre- or postketamine lithium treatment in drinking water. The effects of lithium on ketamine-induced antidepressant-like effects, activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways, oxidative stress, and dendritic spine density in the brain of mice were investigated.

Results:

Subtherapeutic (600mg/L) lithium-pretreated mice exhibited an antidepressant-like response to an ineffective ketamine (2.5mg/kg, intraperitoneally) challenge in the forced swim test. Both the antidepressant-like effects and restoration of dendritic spine density in the medial prefrontal cortex of stressed mice induced by a single ketamine (50mg/kg) injection were sustained by postketamine treatment with 1200mg/L of lithium for at least 2 weeks. These benefits of lithium treatments were associated with activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways in the prefrontal cortex. Acute ketamine (50mg/kg) injection also significantly increased lipid peroxidation, catalase activity, and oxidized glutathione levels in stressed mice. Notably, these oxidative stress markers were completely abolished by pretreatment with 1200mg/L of lithium.

Conclusions:

Our results suggest a novel therapeutic strategy and justify the use of lithium in patients who benefit from ketamine.     

Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson’s disease focusing on correlations with motor symptoms

GeroScience - The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson’s disease (PD)...     

Body composition and newborn birthweight in pregnancies of adolescent and mature women

Teenage pregnancy has been associated with adverse effects for the mother and the newborn (NB). In order to compare body composition (BC) between adolescents (Ad) and mature women (MW) during pregnancy and to determine the difference in birthweight and perinatal morbidity, pregnant Ad (n = 40) and MW (n = 227) were studied. BC changes between the second and third trimesters were determined by multifrequency bioelectrical impedance analysis, and birthweight and NB morbidity were evaluated. During the second and third trimesters of the pregnancy, fat mass was lower in the Ad group [16 kg (13–19)] than in the MW group [22 kg (17–27)] (P < 0.01; median and quartiles 1–3). Fat‐free mass increased by 3.09 kg (2.29–4.20) and 2.20 kg (1.0–3.59) (P ≤ 0.01), and total body water increased by 2.77 L (0.84–4.49) vs. 2.04 L (0.55–3.89) (P = 0.36), in the Ad and MW groups, respectively (median and quartiles 1–3). Birthweight was not significantly different between NBs of Ad (3223 ± 399 g) and NBs of MW (3312 ± 427 g, P = 0.22). The youngest Ad (<18 year old, n = 8) had NB with lower birthweight than MW (3031 ± 503 g, P = 0.06). NBs of Ad mothers showed a non‐significant trend towards a higher rate of morbidity relative to the NBs of MW. In conclusion, the BC of Ad differs from that of MW during pregnancy. In addition, the NB infants of Ad mothers tended to have a lower birthweight than those from MW, a result that suggests that the Ad should be in strict prenatal control.     

Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers

Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic‐induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty‐one healthy volunteers receiving a 10‐mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro‐aripiprazole plasma concentrations were measured by HPLC‐MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin C_max and AUC_0‐12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen.