Prednisone effects on blood-brain barrier permeability and CNS IgG synthesis in healthy humans

Corticosteroids reportedly decrease blood-brain barrier (BBB) permeability and/or IgG synthesis in patients with multiple sclerosis or brain tumors. However, these effects have not been studied in healthy humans. We investigated the effects of prednisone, 80 mg/day for five days, on the ratio of cerebrospinal fluid (CSF) albumin/serum albumin, a measure of blood-brain barrier (BBB) permeability, and on CSF and serum IgG levels in six healthy, normal volunteers. We found significant steroid-induced decreases in serum and CSF albumin levels and in serum IgG levels. However, we found only a nonsignificant decrease in BBB permeability and no significant change in CNS IgG synthesis. These findings, based on a small number of volunteers, suggest that it may be difficult to further decrease BBB permeability and CNS IgG synthesis in medically healthy subjects.     

Interferon-gamma pretreatment of peripheral blood mononuclear cells partially restores defective cytokine production in children with atopic dermatitis

Interferon-gamma (IFN-γ) is considered an important determinant of the balance between T-helper type 1 and 2 cytokines and has been used experimentally for the treatment of atopic dermatitis. However, contrasting results have been reported relative to the Th-UTh-2 cytokine profile in atopic patients. In this study, we examined cytokine production by polyclonally activated peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis, and assessed the influence of in vitro IFN-γ pretreatment on these cells. A fraction of PBMC isolated from children with severe atopic dermatitis, as well as from age-matched controls, was initially exposed to IFN-γ. After washing, both treated and untreated cells were then put into culture either alone or with the addition of phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) plus ionomycin. IL-4, IL-5, IL-10 and IFN-γ production were measured in the supernatants using commercially available ELISAs. PBMC from atopic patients produced more IL-4 (P = 0.04) and IL-10 (P = 0.03) and less IFN-γ (P = 0.01) than controls, when stimulated with PHA. Interestingly, in PMA + ionomycin stimulated cultures, the atopic cytokine profile was different with more IL-5 (P = 0.0068) and less IFN-γ production (P = 0.00046) than the control group. When cells were pretreated with IFN-γ, there were no significant differences between patients and controls. PBMC from children with atopic dermatitis show alterations in cytokine production, compatible in general terms with the Th-l/ Th-2 model. Exposure of PBMC to IFN-γ before activation results in a reduction of these differences, so that cytokine production becomes similar in the atopic and normal groups.     

Serum beta 2 microglobulin in malignant lymphoproliferative disorders

Serum beta-2-microglobulin (S-beta 2M) was measured at diagnosis in 44 patients with lymphocytic leukemias and 47 with malignant lymphomas. Among patients with chronic lymphocytic leukemia (CLL) S-beta 2M was raised (greater than 3 mg/l) in 74% and in 23.5% of those with acute lymphoblastic leukemia (ALL). The frequencies for non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were 59.2% and 40%, respectively. In CLL patients high serum values correlated with large tumor mass, as estimated by Rai's clinical criteria (P less than 0.001), by total peripheral lymphocytes (r = 0.41, P less than 0.05) and by the percentage of bone marrow infiltration of the lymphocytes (P less than 0.01). A significant relation was also found in CLL patients between S-beta 2M level and survival (P less than 0.05). In ALL no association was found between S-beta 2M level with peripheral lymphoblast concentration, French-American-British (FAB) subclassification, splenomegaly, and survival. In NHL patients a significant association was found between S-beta 2M levels and stage of disease (P less than 0.01) and an obscure relation (P less than 0.1) with the presence of lymph nodes greater than 3 cm in diameter, splenomegaly, and hepatomegaly. No significant association was found between S-beta 2M level and histologic subtypes, presence of B symptoms, bone marrow involvement, and survival. In HD patients a significant association was found between the level of S-beta 2M and stage of disease (P less than 0.05) and presence of splenomegaly (P less than 0.05). No association was found between S-beta 2M level and histologic subtypes, lymph nodes greater than 3 cm in diameter, bone marrow involvement, and B symptoms. A significant relation was found between S-beta 2M level and survival in HD patients with widespread disease (P less than .025).     

Microsurgically splinted tubulovasostomy in the rat: modified technique

The fact that splinted tubulovasostomy still yields unsatisfactory results led us to modify the method. We were able to increase the patency of anastomoses by 18%; splint-absorption disturbances could be reduced in 12% of the cases.     

Induction of Immunocellular Resistance to IL-2-Activated Lymphocytes within Ovarian Carcinoma Cells

The development of resistance within ovarian carcinoma cells to activated cytotoxic lymphocytes was the objective of this study. Primary ovarian carcinoma cells were obtained from the ascites of a patient. These cells were cocultured with IL-2-activated autologous tumor-associated lymphocytes (TALs) for 1 week. The resulting selected cells underwent a second coculture for 3 days with IL-2-activated autologous TALs or tumor-infiltrating lymphocytes (TILs). Phenotype analysis of the lymphocytes was performed prior to selection and 4-hr chromium release assays were used to detect resistance induction. Resistance to all effector cells could be demonstrated for the selected cells. However, selected cells maintained in culture demonstrated no difference in cytotoxic susceptibility from unselected cells. The following conclusions were made: (i) rapid immunoselection can occur for ovarian carcinoma in vitro; (ii) the resistance induced is not MHC-restricted; (iii) resistance induced by one type of cytotoxic cell results in general resistance to other types of cell from the same patient; and (iv) this resistance is not maintained during in vitro culture. These results may have direct implications on the future immunotherapy for this condition.     

Noradrenaline uptake inhibition increases melatonin secretion, a measure of noradrenergic neurotransmission, in depressed patients.

Eight patients with endogenous depression who had received no antidepressant treatment for the previous year were treated with the noradrenaline (NA) uptake inhibitor, desipramine (DMI). Pre-treatment plasma melatonin concentrations were normal. After one day of DMI treatment plasma melatonin concentrations were increased but the response was impaired compared to normal subjects. The acute effect of DMI on plasma melatonin persisted after six weeks of treatment. These findings question the hypothesis that beta adrenoceptors are supersensitive in depression and that antidepressant drugs act by down-regulating these receptors.     

Regulation of pregnenolone synthesis in C6-2B glioma cells by 4''-chlorodiazepam.

An experimental model to study synthesis of cholesterol and pregnenolone from the precursor mevalonolactone (MVA) was developed in C6-2B glioma cells. The steroidogenic capability of this cell line and the regulation of pregnenolone production by 4'-chlorodiazepam (4'CD), a specific ligand for the mitochondrial diazepam binding inhibitor (DBI) receptor (MDR), were investigated. Cells maintained in serum-free media were incubated with lovastatin (20 microM) and two inhibitors of pregnenolone metabolism, trilostane (25 microM) and 1,2,3,4-tetrahydro-4-oxo-7-chloro-2-naphthylpyridine (10 microM). Under these conditions the incorporation of [3H]MVA into cholesterol and pregnenolone formation was biphasic, with an initial rapid phase (within 1 min) followed by a slower phase. Cholesterol and pregnenolone were identified by coelution with authentic steroids from a Si 60 Lichrosorb column and gas chromatography/mass spectrometry. Pregnenolone synthesis in intact C6-2B glioma cells was stimulated by nanomolar concentrations of 4'CD after 5 min of incubation with MVA. The stimulatory effect was dependent on drug concentration and the maximal effect was achieved at 10 nM. The time course showed that the incorporation of MVA into pregnenolone is accelerated by the MDR ligand. Cholesterol synthesis is only slightly and not significantly affected by 4'CD. These results support the view that steroid synthesis occurs in a glioma cell line. Moreover, we provide evidence for a rapid steroid synthesis in C6-2B glioma cells, which in turn appears to be accelerated by 1-100 nM 4'CD, a MDR ligand.     

An unusual lateral cervico-facial fistula

Lateral cervical sinuses of fistula are usually derivatives of the branchial clefts and pouches and have a more or less typical course in the neck. We present a patient with an extremely long sinus extending from the left supraclavicular area, via the cheek up to the left infraorbital rim. We could not find a similar report in literature. The diagnostic evaluation as well as the successful surgical removal of the malformation through a skin incision in the neck and a second incision in the sulcus gingivobucalis are described. On the basis of a brief review in the embryology of the congenital anomalies of the neck and face some considerations about the possible origin of the cervico-facial sinuses are discussed.