Venlafaxine treatment stimulates expression of brain-derived neurotrophic factor protein in frontal cortex and inhibits long-term potentiation in hippocampus.

Antidepressant action may involve stimulation of brain-derived neurotrophic factor (BDNF). BDNF also regulates long-term potentiation (LTP). We hypothesized that the 5-HT and norepinephrine reuptake inhibitor, venlafaxine, would stimulate BDNF expression and alter LTP more effectively than the selective 5-HT reuptake inhibitor, citalopram. To test this, we administered venlafaxine or citalopram to rats for 1 or 3 weeks; control rats received vehicle only. We measured BDNF protein in hippocampal and frontal cortex homogenates, and serum. We assessed LTP in area cornu ammonis region 1 (CA1) of in vitro hippocampal brain slices. We also examined input/output function to determine if basal synaptic transmission in area CA1 was altered. Compared to vehicle control, frontal cortex BDNF protein was significantly greater after three, but not one, weeks of venlafaxine treatment. In contrast, citalopram (1 or 3 weeks) did not stimulate BDNF. The stimulatory effect of venlafaxine treatment on BDNF was superimposed on a general time-dependent decrease in expression which was seen in both vehicle control and citalopram-treated animals. LTP was significantly impaired in slices from venlafaxine-treated rats after both 1 and 3 weeks of treatment, but LTP appeared normal in slices from citalopram-treated and vehicle control rats. The LTP impairment caused by venlafaxine treatment was independent of changes in BDNF: LTP was impaired after only 1 week of treatment, prior to any effect on BDNF, and LTP magnitude was not correlated with BDNF protein concentration. Input/output function was significantly but equally reduced after 3 weeks of citalopram, venlafaxine, or control treatment. Decreased BDNF protein in citalopram and vehicle control animals, and decreased input/output function may be consequences of individual housing of animals, which we used to ensure proper dosing. Venlafaxine stimulation of BDNF and inhibition of LTP may be related to the reported effectiveness of venlafaxine in treatment of depression.

Prophylactic placement of gastrostomy feeding tubes before radiotherapy in patients with head and neck cancer: is it worthwhile?

BACKGROUND: After radiation treatment of head and neck cancer, placement of gastrostomy feeding tubes can be technically difficult. The practice of placing tubes before treatment is probably justified if the tube is used for more than 4 weeks and if complications are infrequent. The aim of this study was to determine the outcome of prophylactically placed gastrostomy tubes in patients with head and neck cancer at our institution from 1995 to 1999. STUDY: Data collected retrospectively from the patients' medical records included demographics, duration of tube use, and complications associated with placement. RESULTS: A total of 54 patients (40 men, 14 women) with a mean age of 68.5 years (range, 49-88 years) were studied. Thirty-one patients were treated with both surgery and radiotherapy; 17, with only radiotherapy; and 6, with chemotherapy, radiation, and surgery. The gastrostomy tube was placed before initiation of radiation treatment in 41 patients and after treatment in 13. The method of placement included pull technique (n = 41), introducer technique (n = 10), and surgical (n = 3). Four patients who had a tube placed after treatment required hospitalization for dehydration, whereas no hospitalizations were needed in the prophylactic group. The median duration of tube use was 165 days (range, 0-1,105 days). Only three patients had a complication directly related to placement. CONCLUSION: Gastrostomy tube placement before treatment is appropriate, given the median number of days required for use and limited complications associated with placement.

The counseling role of Baptist ministers in rural and urban West Virginia counties.

It is well established that about half of Americans suffering with a broad range of psychiatric diseases seek ministerial counseling instead of help from the medical community. Less well established is the influence of demographics, such as population density, on the mental health work of ministers. This study compares the counseling activities of Baptist ministers in rural and urban counties of West Virginia. Ministers responded to a questionnaire that assessed basic demographic data as well as attitudes regarding mental illness and counseling activity. County population density was then used to rank respondents. The respondents, who were almost exclusively male, were middle-aged and averaged greater than 20 years of experience in the ministry. They had an average church size of over 200 people. Although greater than 70% reported recent training in ministerial counseling, 85% indicated interest in a workshop focusing on common mental illnesses. No minister reported charging fees for their counseling. Significantly more counseling was reported by ministers from more urban areas with higher per capita incomes and larger congregations.

Co-regulation of pituitary tumor cell adhesion and prolactin gene expression by glucocorticoid.

Rat 235-1 pituitary tumor cells are lactotrophs producing high levels of prolactin (PRL). Dexamethasone (Dex, 100 nM) inhibits PRL gene expression in 235-1 cells by 50%, while simultaneously decreasing cell replication and cell-cell aggregation. To determine the time course of Dex action, we used a quantitative assay for cell-cell interaction, based on the number of single cells present before and after re-aggregation of dispersed cells. 235-1 cells were cultured in growth medium or medium plus 100 nM Dex for 1-4 days before assay. Control cells had 90% re-aggregation on all days of assay. Aggregation of Dex-treated cells decreased to 55% by day 4. Dex treatment also reduced cell numbers by 40%, but this decrease did not contribute to reduced aggregation. To determine the mechanism of Dex-inhibited cell-cell adhesion, we examined the expression of cadherins and catenins. Cadherin-related mRNAs (P- and N-cadherin probes) were detectable in 235-1 cells, but their levels were unchanged by Dex. A pancadherin antibody was unable to detect classical cadherins in these cells. Both alpha- and beta-catenins were detected by Western blotting and their levels were decreased by Dex. Unlike control aggregates, aggregates of Dex-treated cells were able to inhibit expression of PRL mRNA when added to monolayers of 235-1 cells. These data suggest that Dex influences cadherin function by inhibiting catenin expression and that this has the functional consequence of altering 235-1 cell-cell interactions. Overall the data show that Dex affects important aspects of lactotroph function other than PRL gene expression. These changes may include physical alterations in pituitary cell contacts that further support a change in functional state.