Post-receptor-mediated increases in adenylate cyclase activity after chronic antidepressant treatment: relationship to receptor desensitization

Administration to rats of chronic electroconvulsive shock (ECS) or chronic desipramine (DMI, 10 mg/kg daily i.p. for 3 weeks) did not affect either basal or forskolin-stimulated adenylate cyclase activity in membranes prepared from the caudate nucleus. In cerebellar membranes prepared from rats which had received chronic ECS, forskolin-stimulated activity was significantly increased compared to activity in sham- or single ECS treated rats. Forskolin-stimulated adenylate cyclase was increased in both hippocampal and cerebellar membranes from rats which received chronic DMI, compared to saline-treated animals. In cerebellar membranes, increases comparable to those with forskolin were also obtained with guanylyl-5'-imidodiphosphate (GppNHp) after both treatments, while with Mn2+ ions, either alone or in the additional presence of forskolin, the changes observed were similar to those previously reported in cortical membranes. A possible mechanism for these effects was investigated by studying antidepressant-induced and in vitro desensitization of the cyclic AMP response in slice preparations from the various brain areas. In slices from caudate nucleus, chronic DMI did not alter stimulation of cyclic AMP formation by either noradrenaline or forskolin, while in cerebellar slices the noradrenaline response was significantly reduced, and in hippocampal slices both responses were reduced (heterologous desensitization). In vitro incubation of cortical slices with noradrenaline also resulted in a reduction in the response to both agents. However, in membranes prepared from the desensitized cortical slices, there was no change in the degree of activation of adenylate cyclase by either NaF or forskolin. Thus, the increase in these activities, observed in certain brain areas after chronic antidepressant treatment may not necessarily be related to beta-adrenoceptor desensitization.     

Bereavement in combat

Despite the obvious fact that loss and bereavement are an integral part of the war experience, surprisingly little has been written about bereavement and grief in combat. This article discusses reasons for the resistance to the concepts of loss and bereavement in military psychiatry, distinctive aspects of combat bereavement, factors that impede appropriate grieving in war, and, with the aid of case vignettes, the varieties of bereavement states seen in combat situations. The authors conclude that the clinical phenomena of grief run like a connecting thread through the various presentations of combat-related psychiatric syndromes, including post-traumatic stress disorders, and that more research in this area is called for.     

Bucket handle tears of the medial meniscus: meniscal intrusion rather than meniscal extrusion

Objective To determine the frequency of medial meniscal extrusion (MME) versus “medial meniscal intrusion” in the setting of bucket handle tears. Images were evaluated for previously reported risk factors for MME, including: medial meniscal root tear, radial tear, degenerative joint disease and joint effusion. Methods Forty-one consecutive cases of bucket handle tear of the medial meniscus were reviewed by consensus by two musculoskeletal radiologists. Imaging was performed using a 1.5 GE Signa MR unit. Patient age, gender, medial meniscal root integrity, MME, medial meniscal intrusion, degenerative joint disease, effusion and anterior cruciate ligament (ACL) tear were recorded. Results Thirteen females and 27 males (age 12–62 years, median=30 years) were affected; one had bucket handle tear of each knee. Effusion was small in 13, moderate in 9 and large in 18. Degenerative joint disease was mild in three, moderate in two and severe in one. 26 ACL tears included three partial and three chronic. Medial meniscal root tear was complete in one case and partial thickness in two. None of the 40 cases with an intact or partially torn medial meniscal root demonstrated MME. MME of 3.1 mm was seen in the only full-thickness medial meniscal root tear, along with chronic ACL tear, moderate degenerative joint disease and large effusion. Medial meniscal intrusion of the central bucket handle fragment into the intercondylar notch was present in all 41 cases. Conclusion Given an intact medial meniscal root in the setting of a “pure” bucket handle tear, there is no MME.     

Identifying characteristics of children requiring sedation for urodynamics

The aim of this study was to identify characteristics of children requiring sedation for urodynamics. Findings suggest children between the ages of 3 and 7 are more likely to require sedation for urodynamics when compared to other age groups.     

Complex effects of age and gender on hypothermic,adrenocorticotrophic hormone and cortisol responses to ipsapirone challenge in normal subjects

The effects of a challenge dose of the 5-HT_1A agonist, ipsapirone (0.3 mg per kg body weight), or placebo on body temperature and on adrenocorticotrophic hormone (ACTH) and cortisol release, were examined in 30 normal subjects (14 males, 19–74 years and 16 females, 22–69 years) using a randomized, double blind design. Irrespective of age or gender, ipsapirone induced a significant reduction in body temperature relative to placebo and a significant increase in ACTH and cortisol release. Maximal temperature reduction by ipsapirone was significantly blunted in older subjects and was inversely related to age. There was no gender difference in the hypothermic response to ipsapirone. ACTH and cortisol responses showed an opposite impact of aging in males and females. Whereas both responses diminished with age in male subjects, they increased with age in females. The cortisol response of older females was significantly larger than that of all the other subjects. Adverse effects of ipsapirone were also more marked in elderly females and were correlated with ACTH and cortisol responses. These findings should be taken into consideration in the use of ipsapirone and other 5-HT_1A agonists as challenge procedures for studying central serotonergic function in depression and other disorders. Careful matching of control and experimental subjects is indicated so as to avoid spurious results which reflect the effects of age and gender rather than the pathophysiology of the disorders being investigated.     

Reversal by Calcium Ions of the Growth Inhibition of Debaryomyces nicotianae Caused by Antifungal Polyene Antibiotics

Only Debaryomyces nicotianae strain 77, of seven different yeast strains tested, was found to be resistant to heptamycin and other antifungal heptaenes when grown in a rich medium. This strain, however, like the other six, was completely susceptible to these antibiotics in a minimal medium. Addition of yeast extract to the minimal medium abolished the heptamycin effect; calcium ions fully duplicated the effect of yeast extract; Mg(2+) and Mn(2+) were also effective but less so than Ca(2+). Ca(2+) also counteracted the activity of the heptaenes ascosin and trichomycin. Complete reversal of the polyene inhibition by Ca(2+) was obtained if the cation was added simultaneously with the antibiotic; addition of Ca(2+) 2 hr after the polyene was without effect. Addition of Ca(2+) in the absence of the polyene caused a slight, if any, growth stimulation of D. nicotianae 77. Cholesterol also counteracted polyene activity; this was due to the formation of a complex with the antibiotic which prevented the polyene from reaching the site of action-the cytoplasmic membrane. No evidence for complex formation between heptamycin and calcium was found. The importance of Ca(2+) in membrane structure, as evidenced from heptaene studies, is discussed.