Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain

The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females.

We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.     

Clusterin expression in cutaneous CD30-positive lymphoproliferative disorders and their histologic simulants

Background:  Clusterin is a ubiquitous 80 kDa heterodimeric glycoprotein previously shown to be expressed on tumor cells of systemic and, to a lesser extent, primary cutaneous anaplastic large cell lymphoma (PC-ALCL). Lymphomatoid papulosis (LyP), an important differential diagnosis of ALCL, has been studied for clusterin expression in only a small number of cases. The aim of this study was to compare clusterin immunostaining patterns in LyP and other cutaneous histologic simulants with those of PC-ALCL.
Methods:  Formalin-fixed, paraffin-embedded sections of PC-ALCL (6), LyP (20), mycosis fungoides with large cell transformation (MF-LCT, 12), pityriasis lichenoides et varioliformis acuta (PLEVA, 12), arthropod bite reaction (ABR, 12) and lymphomatoid reactions (LR, 9) were immunostained for clusterin and evaluated for staining pattern and distribution. All diagnoses were made with clinicopathologic correlation.
Results:  Characteristic dot-like Golgi staining was identified in 10/20 LyP (50%), 4/6 PC-ALCL (67%) and 9/12 MF-LCT (75%). Two of 12 PLEVA (17%), 1 of 12 ABR (8%) and 2 of 8 LR (25%) had lymphocytes (< 25%) with diffuse cytoplasmic staining. Dermal dendritic cells stained strongly for clusterin. High background staining occurred in some cases.
Conclusion:  Clusterin immunostaining does not reliably distinguish between LyP, PC-ALCL or MF-LCT, but could distinguish LyP from its reactive histologic simulants.     

The course of schizophrenia: Some remarks on a yet unsolved problem of retrospective data collection

Summary The retrospective assessment of symptoms and syndromes is a basic measure in research of the longitudinal course of schizophrenia. In spite of its importance there have been few studies evaluating the standard of quality of instruments for retrospective data collection. Combining retrospectively and cross-sectionally collected data on schizophrenic symptomatology in a cohort study over a period of 5 years revealed a significant underestimation of symptoms when assessed in retrospect. The need for studies on the validity of instruments for the retrospective assessment of symptoms is stressed.     

Pneumatosis cystoides intestinii

Zusammenfassung Die Pneumatosis cystoides intestinii (PCI), das Auftreten submuköser oder subseröser, gasgefüllter Zysten in der Wand des Gastrointestinaltrakts, tritt als seltene Erkrankung ohne eindeutige Geschlechtspräferenz vorwiegend in der 3. bis 5. Lebensdekade auf. Atiopathogenetisch werden unterschiedliche Faktoren diskutiert, am wahrscheinlichsten ist eine bakterielle Ursache (Clostridium perfringens) in Verbindung mit einer minimalen Unterbrechung der Mukosaintegrität. Eine pathognomonische Symptomatik gibt es nicht, das klinische Bild reicht von asymptomatischen Zufallsbefunden bis zur Hämatochezie. Die Diagnose wird durch den Nachweis der Gaseinschlüsse mittels Abdomenübersichtsaufnahme und Kolonkontrasteinlauf gestellt. Als Behandlungsmethoden für symptomatische Patienten stehen Sauerstofftherapie, Antibiotikagabe (Metronidazol) und in schweren Fällen die Resektion des betroffenen Darmabschnitts zur Verfügung.

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Pneumatosis cystoides intestinalis (PCI), a condition involving submucosal or subserosal gas-containing cysts of the wall of the gastrointestinal tract, is a rare entity. It is mostly diagnosed between the third and fifth decades of life without a clear sexual predominance. Different aetiopathogenetic factors are under discussion, the most probable being a bacteriologic cause (Clostridium perfringens) in combination with minimal leaks in mucosal barrier. There are no pathognomonic symptoms; the clinical picture ranges from incidental findings to haematochezia. Diagnosis is based on plain abdominal film and X-ray following barium enema. Methods of treatment in symptomatic cases are oxygen and antibiotic (metronidazole) therapies and, in severe cases, resection of the diseased part of the intestine.

     

Cemented and ingrowth fixation of the Miller-Galante prosthesis. Clinical and roentgenographic comparison after three- to six-year follow-up studies

One hundred thirty-nine cemented and 132 cementless Miller-Galante total knee prostheses were followed between three and six years (average, 43-44 months). The fixation technique was based on patient age, bone quality, and ability to delay full-weight bearing. Clinical follow-up studies were possible on 116 cemented knees. Fifteen knees were lost because of death before the three-year follow-up study, and eight knees required component removal. One hundred twenty-three cementless knees were available for clinical follow-up studies; there were three deaths, and six failures required component removal. No cemented failure was due to fixation, and three cementless failures were due to lack of tibial ingrowth in two and pain of undetermined etiology in one. Preoperative knee scores were slightly significant with cemented knees averaging 48 points and cementless knees averaging 52 points. A similar significant difference was maintained at the final follow-up study. No significant differences were noted for pain, limp, or support scores. Average range of motion was similar in the two groups. Radiolucent lines about the femoral component were rare. Cementless tibial radiolucencies were partial in up to 20% of examined zones, and complete tibial tray radiolucency was seen in only three patients. No correlation between radiolucency and knee scores was seen.     

Carotenoids up-regulate connexin43 gene expression independent of their provitamin A or antioxidant properties.

Epidemiological evidence and studies in whole animals and cell culture have indicated that carotenoids have cancer chemopreventive action. In mouse C3H10T1/2 cells, this activity is highly correlated with the ability of carotenoids to up-regulate gap junctional intercellular communication. Here, we report that in mouse cells, carotenoids increase the expression of connexin43, a gene that encodes a major gap junction protein. This effect appears unrelated to their provitamin A or antioxidant properties, since carotenoids with and without provitamin A activity increased levels of connexin43 mRNA and protein, whereas the antioxidants methyl-bixin and alpha-tocopherol were inactive. Moreover, the active carotenoid canthaxanthin did not induce the vitamin A-inducible gene retinoic acid receptor-beta. Connexin43 is the first carotenoid-inducible gene described in mammals. By indicating an additional pathway through which carotenoids function, these data provide a mechanistic basis for cancer chemoprevention by carotenoids and may lead to a re-evaluation of carotenoid physiology.     

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.