Acute selective serotonin reuptake inhibitors increase conditioned fear expression: blockade with a 5-HT(2C) receptor antagonist.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) effectively treat various anxiety disorders, although symptoms of anxiety are often exacerbated during early stages of treatment. We previously reported that acute treatment with the SSRI citalopram enhances the acquisition of auditory fear conditioning, which is consistent with the initial anxiogenic effects reported clinically. Here, we extend our findings by assessing the effects of acute SSRI treatment on the expression of previously acquired conditioned fear. METHODS: Rats underwent fear conditioning drug-free. Tone-evoked fear responses were tested after drug treatment the following day. This protocol more closely resembles the clinical setting than pre-conditioning treatment, because it evaluates effects of treatment on a pre-existing fear rather than on the formation of a new fear memory. RESULTS: A single pre-testing injection of the SSRIs citalopram or fluoxetine significantly increased fear expression. There was no effect of the antidepressant tianeptine or the norepinephrine reuptake inhibitor tomoxetine, indicating that this effect is specific to SSRIs. The SSRI-induced enhancement in fear expression was not blocked by tropisetron, a 5-HT(3) receptor antagonist, but was blocked by SB 242084, a specific 5-HT(2C) receptor antagonist. CONCLUSIONS: Enhanced activation of 5-HT(2C) receptors might be a mechanism for the anxiogenic effects of SSRIs observed initially during treatment.     

深呼吸 救自己

亏损、信用度下降 美国的医疗卫生行业未能在2008年席卷全球的金融风暴中幸免。2008年9月，股市剧烈动荡、急转直下。近期，美国国家经济研究局（National Bureau of Economic Research）称，美国已经经历了自2007年12月以来最为严重的经济衰退。不仅如此，美国医院协会的一份报告也表示，在2008年8月到11月的选举季期间，有31％的医院经历了不同程度的收入减少，有38％的医院入院人数大幅下降。     

Rapidly progressive lung disease in a patient with cystic fibrosis on long-term azithromycin: possible role of mycoplasma infection.

Macrolides is effective therapy in patients with cystic fibrosis (CF). We describe a girl with CF given long-term azithromycin who died of rapidly progressive lung disease. She was found to have rising titers of mycoplasma serology, suggesting a possible causative role of a resistant mycoplasma infection. Mycoplasma infection should be considered in CF patients who are deteriorating, even if they are being treated with macrolides, to which these organisms are usually susceptible.     

Cardiovascular risk factor prevention in black schoolchildren: two-year results of the "Know Your Body" program

A five-year intervention study of the effectiveness of the "Know Your Body" program in reducing coronary heart disease risk factors among black students in the District of Columbia, who were in grades 4-6 at baseline, was begun in 1983. Nine schools were stratified on socioeconomic status and randomly assigned to control and intervention groups. The "Know Your Body" curriculum focuses on nutrition, fitness, and the prevention of cigarette smoking. At baseline, 1,234 students were eligible for the screening in which the following target risk factors were measured: systolic and diastolic blood pressures, ponderosity index, triceps skinfold thickness, postexercise pulse recovery rate, serum total and high density lipoprotein (HDL) cholesterol, and serum thiocyanate. After two years of intervention, results indicated that the program may have had a favorable impact on the following risk factors: systolic and diastolic pressures, HDL cholesterol, ratio of total to HDL cholesterol, fitness (postexercise pulse recovery rate), and smoking. Significant net changes in the favorable direction also were found for health knowledge and attitude toward smoking. Blood pressure reduction was associated with decreased ponderosity and improved fitness, and increased HDL cholesterol was associated with decreased ponderosity. These results are consistent with other evaluations of the "Know Your Body" program, suggesting that the program may be effective in reducing chronic disease risk in diverse school populations.     

Attitudes towards prenatal diagnosis and carrier screening for cystic fibrosis among the parents of patients in a paediatric cystic fibrosis clinic.

The parents of all children attending the Royal Brompton National Heart and Lung Hospital cystic fibrosis paediatric clinic were asked to complete an anonymous postal questionnaire addressing attitudes towards prenatal diagnosis and population carrier screening for cystic fibrosis (CF); 65% (170/261) of parents responded. Of the respondents, 92% would support the introduction of a population screening test to detect carriers of CF and 19% felt such a test should be mandatory. A total of 64% of CF parents felt they would choose not to have any further children in the knowledge that they were both carriers, 74% would choose to have a prenatal test if they became pregnant, 44% would consider terminating an affected pregnancy, 33% would not, and 23% were unsure. Overall, 72% of respondents indicated they would choose to avoid having a further child with CF either by not having further children or by terminating an affected pregnancy.     

Nonviable Burkholderia mallei induces a mixed Th1- and Th2-like cytokine response in BALB/c mice

Nonviable cell preparations of Burkholderia mallei, the causative agent of glanders, were evaluated as potential vaccine candidates in a BALB/c murine model. Three different B. mallei cell preparations plus Alhydrogel were evaluated: a heat-killed preparation, an irradiation-inactivated preparation, and a preparation of a capsule-negative mutant strain which had been irradiation inactivated. BALB/c mice were vaccinated twice with the different B. mallei preparations, and spleens and sera were collected to determine their cellular and humoral immune responses. All three bacterial cell preparations had essentially the same results in two cellular immune response assays. In a splenocyte proliferation assay, the amount of cell proliferation in response to the homologous immunogen, concanavalin A, or lipopolysaccharide was similar for all the cell preparations. Also, splenocytes from the inoculated mice expressed interleukin 2 (IL-2), gamma interferon, and small amounts of IL-4 and IL-5, and more IL-10 cytokine in the presence of the homologous antigen. When the immunoglobulin subclasses from these mice were examined, they all produced higher levels of IgG1 than IgG2a subclasses. The higher ratio of IgG1 to IgG2a was not due to the amount of the immunogen or the adjuvant (Alhydrogel) used in the BALB/c mice. The cell preparations did not protect the vaccinated mice from a live challenge (>300 50% lethal doses). Our results suggest that in BALB/c mice, a mixed T-helper-cell-like response to nonviable B. mallei is obtained, as demonstrated by a Th1- and Th2-like cytokine response and a Th2-like subclass immunoglobulin response. This may be the reason for the inability of the B. mallei cells that were examined as candidate vaccines to protect the mice from a live challenge.     

Detection of infectious human immunodeficiency virus type 1 in female genital secretions by a short-term culture method

Infectious human immunodeficiency virus type 1 (HIV-1) is difficult to detect in female genital secretions by standard virus culture techniques. To improve detection of cell-free HIV-1 in female genital secretions, we adapted a short-term assay that uses the multinuclear-activation galactosidase indicator (MAGI) assay. When vaginal lavages from HIV-1-infected women were tested with the adapted MAGI assay, 25 (64%) of 39 lavages with detectable, cell-free HIV-1 RNA were shown to have infectious virus. No infectious virus was found in 10 vaginal lavages from HIV-1-infected women with undetectable vaginal viral loads. Significantly (P < 0.01) more lavages from HIV-1-infected women tested positive for infectious virus by the MAGI assay than by standard peripheral blood mononuclear cell (PBMC) coculture, which detected infectious virus in only 6 (17%) of 35 vaginal lavages. Lavages with viral loads of >10,000 copies per lavage yielded significantly (P < 0.01) more positive cultures than those with <10,000 copies by using the MAGI assay. Detection of infectious HIV-1 in vaginal lavages was not associated with the presence of genital tract infections or CD4(+)-T-cell counts. However, although the results were not significant (P = 0.08), the MAGI assay detected infectious virus from more vaginal lavages at a vaginal pH of >/=4.5 than at a pH of <4.5. These results indicate that the MAGI assay is more sensitive than PBMC culture methods for detecting infectious virus in female genital secretions. Accurate measurements of infectious virus in genital secretions will improve studies that evaluate sexual transmission of HIV-1.