Vitamin E reduces antidepressant-related beta-adrenoceptor down-regulation in cultured cells. Comparable effects on St. John's wort and tricyclic antidepressant treatment

The mode of action of antidepressants is still a matter of debate. Acute inhibition of neurotransmitter reuptake in central neuronal synapses, followed by a down-regulation of central postsynaptic beta-adrenoceptor (beta-AR) numbers were consistently observed in vivo, while a reduction in surface beta-AR density was found in cell cultures. Effects of the tricyclic antidepressant desipramine (DMI) were abolished by vitamin E (alpha-TOC) in vitro as well as in vivo. Alpha-TOC interfered with antidepressant-induced changes of cellular plasma membrane properties and with recycling of beta-AR. St. John's wort (SJW) extract reduced beta-AR numbers in cultured cells to a similar extent as DMI or the selective serotonin re-uptake inhibitor fluoxetine. We chronically co-exposed cell cultures to SJW extract and to alpha-TOC. Receptor down-regulation following exposure to the plant extract was inhibited in the presence of alpha-TOC suggesting a mode of action of SJW extract comparable to that of synthetic antidepressants. Inhibition of cell proliferation by the plant extract was also significantly reduced by alpha-TOC.

In vitro effects of bethanechol on smooth muscle preparations from abomasal fundus, corpus, and antrum of dairy cows

Abomasal displacement has been associated with gastric hypomotility. The supply of prokinetic drugs available to address this problem is insufficient. The goal of the study was to investigate the effect of the muscarinic agonist bethanechol (BeCh) on contractility parameters of smooth muscle preparations from several regions of the bovine abomasum (fundus, corpus, and antrum). Cumulative concentration-response curves were constructed using BeCh in vitro with and without pre-incubation with antagonists targeted at M(2) and M(3) muscarinic acetylcholine receptor (mAChR) subtypes. In all preparations investigated, BeCh induced a significant and concentration-dependent increase in all contractility parameters investigated. The maximal attainable effect (V(max)) was more pronounced in circular specimens, and V(max) of antral specimens in circular orientation were significantly lower when compared to the other preparations. Both antagonists caused a rightward shift of the concentration-response curve, suggesting that the effect of BeCh is mediated at least partly by M(2) and M(3) AChRs.

Resistive polymer versus forced-air warming: comparable heat transfer and core rewarming rates in volunteers

BACKGROUND: Mild perioperative hypothermia increases the risk of several severe complications. Perioperative patient warming to preserve normothermia has thus become routine, with forced-air warming being used most often. In previous studies, various resistive warming systems have shown mixed results in comparison with forced-air. Recently, a polymer-based resistive patient warming system has been developed. We compared the efficacy of a standard forced-air warming system with the resistive polymer system in volunteers. METHODS: Eight healthy volunteers participated, each on two separate study days. Unanesthetized volunteers were cooled to a core temperature (tympanic membrane) of 34 degrees C by application of forced-air at 10 degrees C and a circulating-water mattress at 4 degrees C. Meperidine and buspirone were administered to prevent shivering. In a randomly designated order, volunteers were then rewarmed (until their core temperatures reached 36 degrees C) with one of the following active warming systems: (1) forced-air warming (Bair Hugger warming cover #300, blower #750, Arizant, Eden Prairie, MN); or (2) polymer fiber resistive warming (HotDog whole body blanket, HotDog standard controller, Augustine Biomedical, Eden Prairie, MN). The alternate system was used on the second study day. Metabolic heat production, cutaneous heat loss, and core temperature were measured. RESULTS: Metabolic heat production and cutaneous heat loss were similar with each system. After a 30-min delay, core temperature increased nearly linearly by 0.98 (95% confidence interval 0.91-1.04) degrees C/h with forced-air and by 0.92 (0.85-1.00) degrees C/h with resistive heating (P = 0.4). CONCLUSIONS: Heating efficacy and core rewarming rates were similar with full-body forced-air and full-body resistive polymer heating in healthy volunteers.

[Follow-up after malignant tumours of the uterus (cancer of the uterine corpus / cervical cancer)]

Malignant uterine tumours can affect the corpus or the cervix. The endometrial carcinoma with its different histological subtypes counts for most of the malignomas of the uterine body. But the rare category of uterine sarcomas (carcinosarcomas, leiomyosarcomas as well as endometrial stromal sarcomas) also belongs to this group. Cervical cancer presents an own entitity, regarding both histology and therapeutic options. Endometrial cancer is the most common genital malignoma in Northern Europe and North America. Histologically, the endometrial cancer can be subdivided in two groups: type I is hormonal sensitive and well differentiated, type II represents an undifferenciated aggressive tumour with poor prognosis. In general, the patient is elderly. Due to the main symptom - abnormal vaginal bleeding - endometrial cancer is detected in an early stage in about 75% of all patients. First choice in therapy is stage related surgery. Follow-up schemes have not proved yet to improve survival, therefore clear guidelines are missing. National and international groups recommend regular follow-up visits to detect the early vaginal vault relapse which is curable. Cervical cancer is mainly a squamous cell carcinoma and oncogenic Human Papilloma Virus (HPV) associated. Surgery is only indicated up to stage IIA, advanced stages should be treated by radio-chemotherapy. Several studies have shown that follow-up visits can improve survival rates. Intention is the detection of the curable local relapse.

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.

T1(Gd) gives comparable information as Delta T1 relaxation rate in dGEMRIC evaluation of cartilage repair tissue

OBJECTIVES: To evaluate the relationship between T1 after intravenous contrast administration (T1Gd) and Delta relaxation rate (DeltaR1) = (1/T1(Gd) - 1/T1o) in the delayed Gadolinium-Enhanced MRI of cartilage (dGEMRIC) evaluation of cartilage repair tissue. MATERIALS AND METHODS: Thirty single MR examinations from 30 patients after matrix-associated autologous chondrocyte transplantations of the knee joint with different postoperative intervals were examined using an 8-channel knee-coil at 3T. T1 mapping using a 3D GRE sequence with a 35/10 degrees flip angle excitation pulse combination was performed before and after contrast administration (dGEMRIC technique). T1 postcontrast (T1(Gd)) and the DeltaR1 (relative index of pre- and postcontrast R1 value) were calculated for repair tissue and the weight-bearing normal appearing control cartilage. For evaluation of the different postoperative intervals, MR exams were subdivided into 3 groups (up to 12 months, 12-24 months, more than 24 months). For statistical analysis Spearman correlation coefficients were calculated. RESULTS: The mean value for T1 postcontrast was 427 +/- 159 ms, for DeltaR1 1.85 +/- 1.0; in reference cartilage 636 +/- 181 ms for T1 postcontrast and 0.83 +/- 0.5 for DeltaR1.The correlation coefficients were highly significant between T1 (Gd) and DeltaR1 for repair tissue (0.969) as well as normal reference cartilage (0.928) in total, and for the reparative cartilage in the early, middle postoperative, and late postoperative interval after surgery (R values: -0.986, -0.970, and -0.978, respectively). Using either T1(Gd) or DeltaR1, the 2 metrics resulted in similar conclusions regarding the time course of change of repair tissue and control tissue, namely that highly significant (P > 0.01) differences between cartilage repair tissue and reference cartilage were found for all follow-up groups. Additionally, for both metrics highly significant differences (P < 0.01) between early follow up and the 2 later postoperative groups for cartilage repair tissue were found. No statistical differences were found between the 2 later follow-up groups of reparative cartilage either for T1 (Gd) or DeltaR1. CONCLUSION: The high correlation between T1 (Gd) and DeltaR1 and the comparable conclusions reached utilizing metric implies that T1 mapping before intravenous administration of MR contrast agent is not necessary for the evaluation of repair tissue. This will help to reduce costs, inconvenience for the patients, simplifies the examination procedure, and makes dGEMRIC more attractive for follow-up of patients after cartilage repair surgeries.

Cloning and characterization of a novel zinc finger protein (rZFP96) in the rat corpus luteum

The corpus luteum (CL) is a temporary organ involved in the maintenance of pregnancy. In the course of its life-cycle, the CL undergoes two distinct and consecutive processes for its inevitable removal through apoptosis: functional and structural luteolysis. We isolated a gene encoding for a novel rat zinc finger protein (ZFP), named rat ZFP96 (rZFP96) from an ovarian lambda cDNA library. Sequence analysis revealed close sequence and structural similarity to mouse ZFP96 and human zinc finger protein 305 (ZNF305). Quantitative reverse transcription-polymerase chain reaction analysis revealed a positive correlation with the end of pregnancy, that is, the onset of structural luteolysis of the CL. Messenger RNA levels increased 3-fold (P < 0.01) between days 13 and 22 of pregnancy and 8-fold (P < 0.01) between day 13 of pregnancy and day 1 post-partum. In addition, we detected rZFP96 expression in mammary, placenta, heart, kidney and skeletal muscle. Sequence analysis predicted that rZFP96 has a high probability of localizing to the nuclear compartment. The presence of both a perfect consensus TGEKP linker sequence between zinc fingers 2 and 3 as well as several similar sequences between the other zinc fingers suggests physical interaction with DNA. Speculatively, rZFP96 may therefore function as a transcription factor, switching-off pro-survival genes and/or upregulating pro-apoptotic genes and thereby contributing to the demise of the CL.