Treatment of seasonal affective disorders

Seasonal affective disorder (SAD) is a subform of major depressive disorder, recurrent, or bipolar disorder with a regular onset of depressive episodes at a certain time of year, usually the winter. The treatment of SAD is similar to that of other forms of affective disorder, except that bright light therapy is recommended as the first-line option. Light therapy conventionally involves exposure to visible light of at least 2500 lux intensity at eye level. The effects of light therapy are thought to be mediated exclusively by the eyes, not the skin, although this assumption has not yet been verified. Morning light therapy has proven to be superior to treatment regimens in the evening. Response rates to light therapy are about 80% in selected patient populations, with atypical depressive symptoms being the best predictor of a favorable treatment outcome. Data from randomized, controlled trials suggest that antidepressants are effective in the treatment of SAD. Three double-blind, placebo-controlled trials have been conducted showing promising results for the selective serotonin reuptake inhibitors (SSRIs) sertraline and fluoxetine, as well as for moclobemide, a reversible inhibitor of monoamine oxidase A.     

Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1

BACKGROUND: Cell death and survival pathways are critical determinants of epithelial cell fate after ischemia. Forkhead proteins have been implicated in the regulation of cellular survival. METHODS and RESULTS: We have found that none of the forkhead family of proteins, FKHR, is phosphorylated after ischemia/reperfusion in the rat kidney. The time course of phosphorylation is similar to the time course of activation of the forkhead protein kinase Akt/protein kinase B (PKB), with maximal phosphorylation at 24 to 48 hours postreperfusion when the process of regeneration peaks. Extracellular signal-regulated kinase (ERK)1/2 activation has also been implicated as prosurvival in the injured kidney. ERK1/2 were phosphorylated in postischemic kidneys at 5, 30, and 90 minutes of reperfusion, with phosphorylation decreased by 24 and 48 hours. Immunocytochemical analysis revealed increased phospho-ERK1/2 in the thick ascending limb and isolated cells of the S3 segment, which have lost apical actin staining. To understand the relationship between forkhead phosphorylation, Akt, and ERK1/2, an in vitro model of injury was employed. After 40 minutes of chemical anoxia followed by dextrose addition for 20 minutes to replete adenosine triphosphate (ATP) levels, FKHR and FKHRL1 are phosphorylated. The levels of phospho-Akt are increased for at least 120 minutes after dextrose addition with a maximum at 20 minutes. Phosphorylation of Akt, FKHR, and FKHRL1 are phosphatidylinositol 3-kinase (PI 3-kinase) dependent since phosphorylation is reduced by the PI 3-kinase inhibitors, wortmannin, or LY294002. Inhibition of mitogen-activated protein kinase (MAPK)/ERK kinase (MEK1/2), the upstream activator of ERK1/2, has no effect on forkhead protein phosphorylation after chemical anoxia/dextrose addition. CONCLUSION: We conclude that PI 3-kinase and Akt are activated after renal ischemia/reperfusion and that Akt phosphorylation leads to phosphorylation of FKHR and FKHRL1, which may affect epithelial cell fate in acute renal failure.     

Das elektrophoretische Verhalten des Virus der Schweinepest in Agargel und dessen Nachweis mittels der HEIC-Methode

Zusammenfassung Das elektrophoretische Verhalten des Virus der Schweinepest aus infektiösem Serum in Agargel gleicht dem des-Globulins eines Schweineserums. Die Beweglichkeit von Schweinepest-Kulturvirus war geringfügig größer und stimmte mit der des-Globulins des als Kulturmedium verwendeten Kälberserums überein. Diese Befunde deuten auf eine gewisse Beziehung zwischen dem Virus der Schweinepest und dem-Globulin des Serums eines kranken Schweines bzw. des Kälberserums im Kultur-medium. Die Agargel-Elektrophorese stellt eine schnelle und billige Methode zur Untersuchung und Reinigung von infektionstüchtigem, vollvirulentem Schweinepestvirus dar, zu dessen Nachweis die HEIC-Methode herangezogen werden kann.

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Summary The electrophoretic property of swine fever virus (infectious serum) in agar gel is similar to that of the-globuline of swine serum. The mobility of swine fever virus cultured in pig kidney cells was somewhat increased, but corresponded well with that of the-globuline of calf serum used in the tissue culture medium. These data are suggestive of a certain relationship between swine fever virus and the-globuline of serum from infected pigs and also between the virus and the-globuline of the calf serum used in the medium. Agar gel electrophoresis represents a rapid and not expensive method for testing and purifying highly virulent swine fever virus detectable by the HEIC-method.

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Stipendiat der FAO.

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Für umsichtige Mitarbeit danken wir besonders Frl.B. Zoeth, für gewissenhafte technische Assistenz Frl.M. G. Pasini und HerrnE. Schlotterer.     

No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette's disorder patients: a [(123)I]-beta-CIT SPECt-study.

BACKGROUND: There is evidence that Tourette's disorder (TD) is associated with abnormalities in the dopaminergic system involving the dopamine transporter (DAT). Data from [(123)I]-beta-CIT single photon emission computed tomography (SPECT) studies and postmortem findings concerning DAT densities in TD patients are not conclusive. The objective of our study was to measure DAT densities with [(123)I]-beta-CIT binding in TD patients who were either psychotropic drug naive or currently treated with antipsychotics (AP) and healthy controls. METHOD: Altogether 20 TD patients were investigated. A total of 15 patients were psychotropic drug naive and five were currently treated with AP. Ten psychotropic drug naive patients were compared with ten age and sex matched healthy subjects. Five currently treated patients were compared with five age and sex matched psychotropic drug naive TD patients. The investigation was carried out using [(123)I]-beta-CIT (2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane and SPECT. Regions of interest (ROI) were drawn over the striatum and the cerebellum. RESULTS: The DAT densities measured by the striatal/cerebellar (S/C) binding ratio did not differ between drug naive TD patients and the controls. The difference between currently AP treated and psychotropic drug naive TD patients did not reach the level of significance. There was no correlation between the ratio and severity of tics and illness. CONCLUSION: Our study with psychotropic drug naive TD patients contributed to clarify the inconsistent results concerning the DAT.     

Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study

Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in design and did not consider the existence of pathologically distinct processes. The Bruneck Study is a prospective survey in the general community (age range, 40 to 79 years). The baseline examination and first reevaluation were performed in the summers of 1990 and 1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and advanced (incidence and/or progression of stenosis >40%) stages of atherogenesis were differentiated. The risk profile of early atherogenesis consists of traditional risk factors, such as hypertension, hyperlipidemia, and cigarette smoking (pack-years), supplemented by a variety of less well-established risk conditions, including high body iron stores, hypothyroidism, microalbuminuria, and high alcohol consumption. In contrast, the risk profile of advanced atherogenesis includes markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and clinical conditions known to interfere with coagulation: high fibrinogen, low antithrombin, factor V Leiden mutation, lipoprotein(a) >0.32 g/L, high platelet count, cigarette smoking, and diabetes. Hyperlipidemia and hypertension were of only minor relevance. These findings, along with the epidemiological features of advanced atherogenesis and emergence of an elevated fibrin turnover, suggest atherothrombosis to be a key mechanism in the development of advanced stenotic atherosclerosis. Supplementary 6-category logistic regression models illustrate the changing association between major risk predictors and atherosclerosis of increasing severity and substantiate appropriateness of the 40% threshold applied for the definition of advanced stenotic atherosclerosis. Atherosclerosis is a heterogeneous process that subsumes etiologically and epidemiologically distinct disease entities. The multifactorial etiology of atherosclerosis, which goes far beyond the traditional risk factors, has not yet achieved adequate attention in clinical practice and disease prevention.     

Allergic rhinitis, asthma, and atherosclerosis in the Bruneck and ARMY studies

BACKGROUND: Several diseases characterized by chronic inflammation and immune activation have been linked to enhanced risk for atherosclerosis. The potential association between allergies and atherosclerosis, however, remains to be defined. METHODS: The association between common allergic diseases (allergic rhinitis and asthma) and 5-year development and progression of carotid atherosclerosis (Bruneck Study) and high intima-media thickness in carotid and femoral arteries (Atherosclerosis Risk Factors in Male Youngsters [ARMY] study) was investigated. The Bruneck Study is a prospective population-based survey of 826 men and women aged 40 to 70 years; the ARMY study is a cross-sectional evaluation of 141 men aged 17 or 18 years. RESULTS: Subjects with allergic disorders were at a significantly increased risk for high intima-media thickness in the ARMY study (odds ratio, 2.5; 95% confidence interval, 1.1-5.5; P=.03) and for atherosclerosis development and progression in the Bruneck Study (odds ratio, 3.8; 95% confidence interval, 1.4-10.2; P=.007). The associations remained significant after multivariate adjustment for a broad array of established and potential vascular risk factors. When IgE levels were substituted for the clinical allergy variable, findings were confirmed in the Bruneck Study (adjusted odds ratio, 1.7; 95% confidence interval, 1.1-8.0), for a 1-SD increase in IgE level (P=.02). CONCLUSIONS: This study documents enhanced atherosclerosis among subjects with common allergic diseases. Our findings fit well with the emerging concept that key components of allergies, such as leukotrienes or mast cells, are active in human atherogenesis and further extend the growing list of immune system-mediated and chronic inflammatory disorders that have been linked with enhanced risk for atherosclerosis.     

Characterization of gait variability in multiple system atrophy and Parkinson’s disease

Journal of Neurology - Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. We compared...     

Reboxetine in a patient with seasonal bulimia resistant to SSRIs and light therapy

There is a phenomenological similarity between seasonal affective disorder and bulimia nervosa, as sufferers from both show increased appetite and carbohydrate craving and probably share a common dysfunction in brain serotonergic systems. Serotonergic compounds and bright light therapy have proven to be an effective treatment for both disorders. We describe the case of a woman who suffered from seasonal affective disorder and nonpurging bulimia nervosa for 16 years and was resistant to treatment regimens with selective serotonin re-uptake inhibitors and bright light therapy. She was successfully treated with the selective noradrenaline re-uptake inhibitor reboxetine. The authors want to encourage clinicians to make attempts to treat seasonal and non-seasonal bulimia with selective noradrenergic compounds.