Role of cytokines in the progression of renal damage in IgA nephropathy

Summary: IgA nephropathy, or Berger's disease (IgAN), is a worldwide disease which is characterized by a slowly progressive loss of renal function accompanied by decreasing kidney size with the development of glomerulosclerosis and interstitial fibrosis. Immunologic and non-immunologic factors are implicated in the progression of renal damage, since they are potent inducers in stimulating glomerular, tubular and interstitial cells and non-resident cells to produce free oxygen radicals, cytokines, growth factors, chemokines, etc. Recent data from our laboratory and other groups, synthesized in this review, have demonstrated the remarkable involvement of these humoral factors in the progression of renal damage in IgAN patients. Therefore, prospective therapeutic approaches have been suggested in blocking the inflammatory mediators during the pathophysiologic sequelae of immune and non-immune mechanisms which may intervene in the outcome of the disease.     

Plasminogen activators and plasminogen activator inhibitors in liver deficiencies caused by chronic alcoholism or infectious hepatitis

Plasma concentrations of tissue-type plasminogen activator (t-PA), urokinase (u-PA), plasminogen activator inhibitor 1 (PAI-1) and PAI-2 were studied in 53 patients with liver deficiency caused by chronic alcoholism (n = 40), viral hepatitis (n = 10) or malignant disease of the liver (n = 3) and compared to that of a control group (n = 20) of healthy subjects. u-PA and PAI-1 levels were significantly increased in all patients with chronic alcoholism, whereas high t-PA was only observed in combination with disturbed liver function tests or with liver cirrhosis (two and six-fold above control values, respectively). A good correlation was observed between t-PA and gamma glutamyl transferase (r = 0.615; p less than 0.001). In patients with infectious hepatitis or with malignant disease of the liver t-PA was normal whereas u-PA and PAI-1 were increased. PAI-2 levels were close to or below the detection limit (15 ng/ml) in the control group and in most patients. However, in two patients with alcohol induced cirrhosis PAI-2 levels were approximately 45 ng/ml and in one patient with hepatocarcinoma even 66 ng/ml. Thus, in liver disease, marked elevations of t-PA, u-PA and PAI-1 levels may occur, with increased PAI-1 as an early marker of liver defects and t-PA a marker of severe liver defects.     

KGF-transfected cells can stimulate growth and proliferation of human cultured keratinocytes in vitro

Objective: To establish two stably KGF-transfected, immortalized cell lines. Methods: HaCaT-keratinocytes and KMST-6-fibroblasts were transfected by liposome mediated gene transfer. Transfection effectivity, gene integration and configuration of the transgenic protein were investigated by ELISA, DANN-PCR and β-Gal-staining. Results: Most effective GF producing clones were tested by a colorimetric XTT-test. Conclusion: This is a significant acceleration of cell proliferation and mitosis of human keratinocytes in an Air Liquid Interface (ALI) test system.     

Distribution and genesis of the RFRP-producing neurons in the rat brain: Comparison with melanin-concentrating hormone- and hypocretin-containing neurons

Prepro-RFRP-containing neurons have recently been described in the mammalian brain. These neurons are only found in the tuberal hypothalamus. In this work, we have provided a detailed analysis of the distribution of cells expressing the RFRP mRNA, and found them in seven anatomical structures of the tuberal hypothalamus. No co-expression with melanin-concentrating hormone (MCH) or hypocretin (Hcrt), that are also described in neurons of the tuberal hypothalamus, was observed. Using the BrdU method, we found that all RFRP cell bodies are generated between E13 and E14.Thus, RFRP neurons form a specific cell population with a complex distribution pattern in the tuberal hypothalamus. However, they are generated in one peak. These observations are discussed with data concerning the distribution and genesis of the MCH and Hcrt cell populations that are also distributed in the tuberal hypothalamus.     

Snake bites by the jararacucu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in Sao Paulo State, Brazil

The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in Sao Paulo State, Brazil. We examined 29 cases of proven jararacucu bites recruited over a 20-year period in two Sao Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care- unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.      

Loading-induced changes in synovial fluid affect cartilage metabolism

The purpose of this study was to determine whether changes in the synovial fluid (SF) induced by in vivo loading can induce an alteration in the metabolic activity of chondrocytes in vitro. Therefore, SF was collected from ponies after a period of box rest and after they had exercise for a week. Normal, unloaded articular cartilage explants were cultured in 20% solutions of these SFs for 4 days and chondrocyte activity was determined by glycosaminoglycan (GAG) turnover. In explants cultured in post-exercise SF, GAG synthesis was enhanced and GAG release was diminished when compared to cultures in pre-exercise SF. SF analysis showed that levels of insulin-like growth factors (IGF- I and IGF-II) tended to be higher in post-exercise SF, while no differences were found in metalloproteinase activity, hyaluronic acid and protein concentrations. This study showed that anabolic effects of joint loading on cartilage are, at least partially, mediated by alterations in the SF.      

Surface markers of human eosinophils

Peripheral blood eosinophils from patients with eosinophilia and from healthy subjects were studied for surface immunoglobulins, receptors for the Fc region of IgG, complement receptors, and spontaneous rosette formation with sheep and mouse erythrocytes. Eosinophils were found to have receptors for complement and for aggregated IgG, and to have the same two types of complement receptors as do lymphocytes and monocytes. Immune adherence type receptors were specific for C4 or C3b, while C3d receptors were specific for C3d but unreactive with C4. Eosinophils differed from fully mature neutrophils in that the former had C3d receptors and relatively weak immune adherence (C4 or C3b) receptors, while the later did not have the C3d receptors and had strong immune adherence receptors. Eosinophil phagocytosis of complement-receptor bound erythrocytes was dependent on the presence of IgG in the antibody coating the red blood cells; this requirement for IgG resembled that found in neutrophil phagocytosis. No surface Ig or spontaneous erythrocyte rosette formation was observed with eosinophils.     

Localization of electrodes in the subthalamic nucleus on magnetic resonance imaging

OBJECT: The authors describe a new method of localizing electrodes on magnetic resonance (MR) images and focus on the positions of both the most efficient contact and the electrode related to the MR imaging target. METHODS: Thirty-one patients who had undergone bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) were included in this study. Target coordinates were calculated in the anterior commissure-posterior commissure referential. A study of the correlation between the artifact and the related contact allowed one to deduce the contact position from the identification of the distal artifact on MR imaging. The best stimulation point corresponded with the contact resulting in the best Unified Parkinson's Disease Rating Scale (UPDRS) motor score improvement. It was compared (Student t-test) with the dorsal margin of the STN (DM STN), which was determined electrophysiologically. The distance between the target and the electrode was calculated individually in each axis. The best stimulation point was located at anteroposterior -2.34 +/- 1.63 mm, lateral 12.04 +/- 1.62 mm, and vertical -2.57 +/- 1.68 mm. This point was not significantly different from the DM STN (p < 0.05). The postoperative UPDRS motor score was 28.07 +/- 12.16, as opposed to the preoperative score of 46.27 +/- 13.89. The distance between the expected and actual target in the x- and y-axes was 1.34 +/- 1.02 and 1.03 +/- 0.76 mm, respectively. In the z-axis, 39.7% of the distal contacts were located proximal to the target. CONCLUSIONS: This approach proposed for the localization of the electrodes on MR imaging shows that DBS is most effective in the dorsal and lateral part of the STN and indicates that the DBS electrode can be located more proximally than originally expected because of the caudal brain shift that may occur during the implantation procedure.