The role of IL-17 in systemic lupus erythematosus and its potential as a therapeutic target

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies production and immune complex deposition with systemic clinical manifestations. Interleukin (IL)-17-producing cells play a crucial role in disease pathogenesis and represent an attractive therapeutic target.

Areas covered: This review provides an update on the possibility of targeting IL-17 in SLE. The rational for this approach as well as currently available and future targets are discussed.

Expert opinion: Although human expression studies and animal models indicate that IL-17 blocking may be a promising therapeutic strategy for SLE, direct evidence for IL-17 inhibition in SLE patients is unavailable. Biologic therapies and small-molecule drugs that target IL-17 production are required for the achievement of a favorable clinical effect in SLE patients.     

Reciprocal heterotopic callosal connections between the two striate areas in Tupaia

Summary WGA-HRP injections were placed into area 17 close to the border with area 18 of Tupaia belangeri in order to study the callosal connections of the striate area in this animal. Most callosal neurons were found in the striate cortex (57.6–86.9%), some in the extrastriate area 18 (10.6–28.1%), and a few in even more temporal regions (2.5–14.3%). Concerning only the area 17, reciprocal homotopic connections could be observed as a strip along the area 17/18 border. Additionally, heterotopic callosal connections could be seen in regions representing the binocular visual field, especially the lower part. The area 17 cells were mostly located in the supragranular layers II and III (94.1–97.2%). But neurons could also be found in the infragranular layers, especially layer VI (2.6–5.2%) and in layer IV (0.2–1.1%). Homotopic projections were mostly seen in layers IIIc and V. The majority of the supragranular and infragranular neurons are pyramidal cells. However, a newly defined subpopulation of neurons, most probably stellate cells, were discovered forming a band in sublayer IIIc, very close to the layer III/IV border.     

Nonimmune hydrops fetalis: a challenge in perinatal pathology

Autopsies were performed in 40 cases of nonimmune hydrops fetalis during the period from 1975 to 1983. In 25 cases specific anatomic diagnoses, including hematologic disorders, infections, chromosomal abnormalities, congenital anomalies, and tumors, were made. In the majority the diagnosis of hydrops fetalis was made prenatally by ultrasonography. The mean gestational age at delivery was 30 weeks; 23 infants were stillborn, and 17 died during the neonatal period. Body weights were consistently increased; peripheral edema and ascites were present in all cases and pleural effusions in all but two cases. Hepatosplenomegaly, cardiomegaly, and pulmonary hypoplasia were frequent findings. The most consistent microscopic changes involved endocrine organs. Islet cell hyperplasia and Leydig cell hyperplasia were common, and thyroid hyperplasia was found occasionally. The fetal zone of the adrenal cortex was often thick and composed of swollen, vacuolated cells. Enhanced extramedullary erythropoiesis was observed in all cases. Thirty-nine placentas were examined; 34 were edematous (mean weight, 547 g), with villous edema, excess erythroblastemia and normoblastemia, and occasional intravillous hematopoiesis. Nonimmune hydrops fetalis has a range of known causes. Thorough autopsy, including placental examination, is the most useful approach for determining the etiology. In 23 cases the probable or possible cause was established in this manner. Antibody studies should also be performed in all cases to exclude an immunologic etiology. Synthesis of clinical, serologic, and pathologic data offers prospects for rational management and prediction of recurrence.     

Neuronal connection of the cortex and reconstruction of the visual space

The distributions of retrograde labeled cells in fields 17 and 18 and the fields 17/18 transitional zone were studied in both hemispheres of cats after microiontophoretic administration of horseradish peroxidase into individual cortical columns in fields 17, 18, 19, and 21a. The clustered organization of the internal connections of the cortical fields, the asymmetrical locations of labeled callosal cells relative to the injected columns, and the defined distribution of labeled cells in layers A of the lateral geniculate body suggested that eye-specific neuronal connections support binding of the visual hemifields separately for each eye. Application of marker to columns in fields 19 or 21a demonstrated disparate inputs from fields 17 and 18 and the fields 17/18 transitional zone. It is suggested that these connections may support the extraction of loci and stereoscopic boundaries located in the central sectors of the visual space.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 10, pp. 1281–1290, October, 2003.     

Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice

We previously showed that one subcutaneous (sc) injection of 5-androstene-3beta,17beta-diol (AED) stimulated the innate immune system in mice and prevented mortality due to hemopoietic suppression after whole-body ionizing irradiation with gamma rays. In the present study, we tested whether there was any significant toxicity in mice that might hinder development of this steroid for human use. There were no indications of toxicity in chemical analyses of serum after sc doses as high as 4000 mg/kg. At this dose, 2 of 54 mice died when given AED alone. When 4800 mg/kg was given orally, no deaths resulted. The only adverse findings attributed to AED administration were 1) a moderate elevation of granulocytes in abdominal organs and fat after sc injections of 320 mg/kg; and 2) occasional wasting of skin over the injection site in female B6D2F1 but not male C3H/HeN mice. Significant weight loss (6%) was observed after sc injections of 320 mg/kg but not 160 or 80 mg/kg. When male C3H/HeN mice were injected sc with AED at doses of 0-200 mg/kg 24 h before whole body gamma-irradiation (9 Gy), a significant improvement in survival was observed at doses as low as 5 mg/kg. Oral administration of AED produced significant survival enhancement at a dose of 1600 mg/kg. We conclude that the radioprotective efficacy of AED is accompanied by low toxicity.Androst-5-ene-3 beta, 17 beta-diol; Ionizing radiation; Experimental radiation injuries; Toxicity; Clinical chemistry; Histopathology     

Evidence that the different classes of relay cells of the cat's lateral geniculate nucleus terminate in different layers of the striate cortex

Summary Small electrophoretic injections of horseradish peroxidase (HRP) were made with recording microelectrodes in different layers of area 17 of the cat. The sizes and locations of labeled relay cells in the lateral geniculate nucleus (LGNd) were then studied. Layer I was found to receive inputs mainly from small LGNd cells (13–21 m). These cells were located in the parvocellular C laminae and the MIN. Layer II and the upper portion of layer III were not found to receive LGNd afferents. Lower layer III was found to receive inputs mainly from small to medium-sized relay cells. These cells were located in the A laminae and the parvocellular C laminae. Layer IVab and the layer III-IV border region were found to receive afferents from predominantly large LGNd neurons (> 20 m). These cells were located in laminae A, A₁; C, and the MIN. Layer IVc was found to receive inputs from mostly small to medium-sized cells (15–23 m). Nearly all of these cells were in the A laminae although some small cells in laminae C were observed following layer IVc injections which involved the layer IV–V border region. Layer V, away from the layer IV–V border region, was not found to receive LGNd afferents. Finally, layer VI was found to receive inputs from both large and small relay cells. These cells were all located in the A laminae.In the light of previous findings, these results suggest that the terminals of W, X, and Y cell axons are segregated within the cat's striate cortex: W cells projecting to layer 1, the deeper portion of layer III and the layer IV–V border region; X cells projecting heavily to layer IVc with a minor projection to layer VI and possibly also to lower layer III; Y cells projecting heavily to layer IVab and the layer III–IV border region with a smaller projection to layer VI.     

Induction of ovulation in rabbits by pure urinary Iuteinizing hormone

In 18-week-old nulliparous rabbit dose, ovulation was inducedwith 50 IU of pure urinary luteinizing hormone (LH; LHgroup),or 50 IU of ohuman chorionic gonadotrophin (HCG; HCG group),in order to detemine the effect of these treatments on 17-oestradioland progesterone concentrations, and on oocyte and embryo quality.Luteinizing follicles, recovered oocytes, progesteronoe concentrationand grade 5 embryos were significantly reduced when pure urinaryLH was used. Statistically significant correlations were found:(i) between oestradiol concentration and number of degeneratedoocytes in both groups (positive); (ii) between oestradiol concentrationand grade 1 and 2 embrayos (negative), and grade 5 embryos (positive)in the HCG group; (iii) between progesteronoe concentrationand metaphase II oocytes(negatice), and between progesteroneand grade 5 sembryos (positive), in the HCG group; and (iv)between progesterone and oestradiol concentrations (negative)in the LH group. It seems that the oestrsdiol to progegsteroneratio improves during the early luteal phase when ovulationis induced with LH, and that oestradiol and progesterone concentrationscould play a role in dtermining oocyte and embryo quality     

Two 14q+ chromosomes in malignant lymphoma: crucial cytogenetic changes on 14q

We encountered a 36-year-old white male patient with poorly differentiated lymphocytic lymphoma, whose lymph node cells showed a clonal cytogenetic change involving chromosome #14, i.e., 47,XY, + 2,der(14),t(14;14)(14pter----14q32;14q24----14q32++ +). In addition to this change, cells with a translocation between chromosomes #2 and another #14 [t(2;14)(q21;q24)], as well as a missing chromosome #8 were found. We have reviewed the literature dealing with two or more changes affecting chromosome #14 and discussed the importance of the cytogenetic change at band 14q32 in malignant lymphoma.     

Do Eye Hospitals Have a Role in Our Future?

Eye hospitals, originally founded to care for the poor, have developed into academic centers and tertiary "hospitals of last resort." Inexorable economic pressures, especially price competition, are likely to close many of them, particularly those which are marginal in quality or management. Survival of the remainder may further depend on their ability to adapt to a rapidly changing environment and to fulfill, better than anyone else, the special mission of basic and clinical research and training. Society must be convinced that some of these complex, highly differentiated, relatively expensive eye hospitals are significant national resources, serve the public welfare, and are worth preserving.     

Effect of a single administration of ketoconazole on total and physiologically free plasma testosterone and 17β-oestradiol levels in healthy male volunteers

Summary The effect of a single oral dose of 400 mg ketoconazole, given as an 80 mg/ml suspension, on total and physiologically free (i.e. non-sex hormonebound) testosterone and 17-oestradiol has been investigated in 6 healthy male volunteers. The two steroids fell to nadir levels of 18 and 60% of their respective initial concentrations 6 hours after drug intake, and then completely recovered. Although in vitro slight displacement of testosterone from the sex-hormone binding globulin, by high doses of ketoconazole was found, the physiologically free concentration of testosterone in vivo was closely correlated with that of the total hormone, suggesting that there is no direct interference with sex-hormone binding globulin in vivo. Plasma LH and FSH were not significantly modified by treatment. The effect of ketoconazole on plasma oestradiol levels was less pronounced and was not clearly related to a block of the aromatase system, as reported in vitro.This work was presented in part at the International Symposium on the Regulation of Androgen Actions, Montreal, 29th June–1st July 1984