Dexamethasone

Our aim was to study histopathological changes in lung tissue at the light microscopic and ultrastructural level during recovery from immunosuppression and Pneumocystis carinii pneumonia. Male Wistar rats were immunosuppressed by per oral dexamethasone for 12 weeks to induce P. carinii pneumonia, after which dexamethasone was stopped. Recovery was monitored 1, 2 and 4 weeks after cessation of the immunosuppression. In immunosuppressed animals, CD4+ and CD8+ lymphocytes were both decreased in situ. CD8+ lymphocytes increased above control level at week one. Like CD8+ cells, the ED1+ macrophages increased rapidly in situ. This was accompanied by a progressively increasing migration (more transient for lymphocytes) of macrophages into bronchoalveolar fluid, associated with morphological signs of activation and phagocytosis and proliferation of type II pneumocytes. Bronchoalveolar lavage (BAL) fluid tumour necrosis factor-alpha (TNF-alpha) increased from subnormal levels to a 4 week pea...

The intestine of poultry plays a significant role in the health and production through enzymatic and microbial digestion of feed as well as absorption of nutrients. The current study was designed to explore the gross and histological alterations in the broiler duodenum and cecum triggered by dietary dexamethasone (DEX). The study was conducted on four homogenous groups of one-day-old chicks (20 chicks/group) i.e. one control (Non-DEX) and three treatment groups (DEX-1, DEX-2, and DEX-3). The broilers were fed commercial broiler feed containing DEX at the rate of 0, 3, 5, and 7mg/kg feed in the Non-DEX, DEX-1, DEX-2, and DEX-3 groups, respectively. The gross morphologic and morphometric data were recorded immediately after the collection of samples on days 7, 14, 21, and 28. Then, the tissue samples were processed for histological investigation. In the gross morphometric study, the weight, length, and width of the intestine were found significantly less in the DEX groups. Histopathological study results showed degeneration of intestinal glands (duodenum), mucosa, and lymphatic nodules with loss of lymphatic nodules (cecum). The percentage of the degenerated nodule was also increased. The length, width, and surface area of the duodenal villi, thickness of the mucosal layer of the cecum, and diameter of the cecal lymphatic nodules were substantially decreased in all the DEX groups. The magnitude of the alterations was associated with both the dose and duration of DEX treatment. However, the current study results indicate that DEX treatment significantly alters the morphologic and morphometric characteristics of the broiler intestine.

Many studies reported an improved prognosis in the patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease (i.e. Burkitt's cell leukemia) has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of the Burkitt's cell leukemia (BL) patients with similarly treated and not transplanted other types of acute lymphoblastic leukemia (ALL) patients and with ALL cases that underwent allogeneic stem cell transplantation (ASCT) in their first remissions. In this retrospective analysis, BL patients aged between 16 and 63 who admitted between 2000 and 2014 to Hacettepe or Gazi University Hospitals and treated with intensive therapies aiming cure were included in the study. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NTxALL group) and all ALL patients who underwent ...

Articular cartilage lacks self-repair capacity. Currently, two methods employing autologous cells are used to stimulate repair of articular cartilage. Micro-fracture induced repair induces autologous mesenchymal cell migration from bone marrow. Autologous chondrocytes' transplantation involves in vitro expansion of chondrocytes, and later implantation. In 15 patients de-differentiated chondrocytes obtained by cartilage biopsy were compared to cells derived from repair tissue induced by micro-fracture. These patients all underwent micro-fracture during the cartilage biopsy procedure. Autologous chondrocytes' transplantation was performed at least two months later then the biopsy. Tissue bits from articular cartilage and micro-fracture repair tissue were incubated in-vitro and explant cell cultures established. The cell cultures were assessed by immunohistochemistry and induced to differentiate. Differentiation into bone tissue was stimulated by addition of basic fibroblast gr...

Background: The clinical features, therapy and outcome of anthrax cases from the Elazig province (the eastern Anatolian region) of Turkey seen in our clinic over an 8-year period were reviewed. Patients and Methods: The records of 25 anthrax cases observed in our clinic during the period January 1994 to April 2002 were examined. Results: All cases were cutaneous; 18 (72%) patients exhibited malignant pustules and seven (28%) malignant edema. Three of the patients with a malignant pustule developed anthrax sepsis when admitted to our clinic. All cases were treated with penicillin. One patient who had penicillin allergy was treated with ciprofloxacin. In addition, patients with malignant edema were also treated with systemic corticosteroids (methylprednisolone or dexamethasone). Two patients died due to anthrax sepsis; one case with anthrax sepsis recovered. The mortality rate was 8%. Discussion: Anthrax is still a reality in Turkey. Cutaneous anthrax should be considered in any patient with a painless ulcer with vesicles, edema and a history of exposure to animals or animal products. In our series, penicillin and ciprofloxacin were effective in treatment of anthrax. Our anthrax sepsis case demonstrates that anthrax sepsis is not always fatal if antibiotic treatment is given early after diagnosis.

Autophagy occurs in tumor cells acquiring cytotoxic drug resistance and its activation may impair their susceptibility to apoptosis in response to apoptogen agents. We investigated the pro-apoptotic effect of dexamethasone (Dex) on MM cell lines (U266, INA-6, LR5-8226, LIG, and MCC2) and primary malignant plasma cells from naïve and refractory/relapsed patients. We evaluated the transcriptional and ultrastructural events leading to autophagy by measuring Beclin-1 and p62 levels and transmission electronic microscopy. Autophagy was inhibited by hydroxychloroquine (HCQ), whereas the ability of Dex-resistant MM cells to recover the susceptibility to apoptosis was measured. A direct relationship between autophagy and Beclin-1 or LC3/Atg8 levels was observed, whereas their mRNAs were inversely correlated to p62 expression. Starvation strongly activated autophagy by inducing cellular, transcriptional, and ultrastructural modifications that were reversed by HCQ. Taken together, these data ...

Growth of very low birthweight (VLBW) infants is used to monitor nutrition and intrauterine velocity is taken as the desired goal.We hypothesised that beside nutrition growth failure is caused by disease severity.Prospective longitudinal study of 45 VLBW infants undergoing intensive care, mechanical ventilation was used as proxy to disease severity. Nutritional intake, body weight, length, head circumference, and lower leg length (LLL) were measured during the first 5 weeks of life.Birthweight and gestational age were lower in 22 ventilated than in 23 unventilated infants (p < 0.01). Median daily intake was 3.2 and 2.8 g/kg for protein (n.s.), 108 and 112 kcal/kg for energy (n.s.), 175 and 160 ml/kg for volume (p < 0.01) up to day 35, respectively. Chronic lung disease occurred in 12 infants, five of whom were treated with dexamethasone. Artificial ventilation (p < 0.01) and dexamethasone treatment (p < 0.05) were independent predictors of weight gain. Median weight gain (8.2 and 9.7 g/kg/d), head growth (0.45 and 0.60 cm/week), and LLL growth (0.28 and 0.35 mm/d) were lower (p < 0.05) in ventilated than in non-ventilated infants, respectively. The correlation of LLL growth with body length (r = 0.31, p < 0.05) and head growth (r = 0.42, p < 0.01) was weak. Dexamethasone arrested growth; median LLL gain was 0.21 and 0.31 mm/d in ventilated infants with and without dexamethasone (p < 0.05).In VLBW infants, fetal growth rates are not reached with current feeding practice. In addition to inadequate nutrition, factors directly related to disease and treatment contribute to postnatal growth failure.

Background The cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) mediated phosphorylation of glucocorticoid receptor (GR) exerts opposite effects on GR transcriptional activity and affects other posttranslational modifications within this protein. The major phosphorylation site of human GR targeted by MAPK family is the serine 226 and multiple kinase complexes phosphorylate receptor at the serine 211 residue. We hypothesize that GR posttranslational modifications are involved in the determination of the cellular fate in human lymphoblastic leukemia cells. We investigated whether UV signalling through alternative GR phosphorylation determined the cell type specificity of glucocorticoids (GCs) mediated apoptosis. Results We have identified putative Glucocorticoid Response Elements (GREs) within the promoter regulatory regions of the Bcl-2 family members NOXA and Mcl-1 indicating that they are direct GR transcriptional targets. These genes were differentially regulated in CEM-C7-14, CEM-C1-15 and A549 cells by glucocorticoids and JNK pathway. In addition, our results revealed that the S211 phosphorylation was dominant in CEM-C7-14, whereas the opposite was the case in CEM-C1-15 where prevalence of S226 GR phosphorylation was observed. Furthermore, multiple GR isoforms with cell line specific patterns were identified in CEM-C7-14 cells compared to CEM-C1-15 and A549 cell lines with the same antibodies. Conclusions GR phosphorylation status kinetics, and site specificity as well as isoform variability differ in CEM-C7-14, CEM-C1-15, and A549 cells. The positive or negative response to GCs induced apoptosis in these cell lines is a consequence of the variable equilibrium of NOXA and Mcl-1 gene expression potentially mediated by alternatively phosphorylated GR, as well as the balance of MAPK/CDK pathways controlling GR phosphorylation pattern. Our results provide molecular base and valuable knowledge for improving the GC based therapies of leukaemia.

Treatment of HC11 mouse mammary epithelial cells with the lactogenic hormones dexamethasone, insulin, and prolactin (DIP) leads to cellular differentiation and production of the milk protein beta-casein. The following experimental evidence suggests the involvement of protein kinase C (PKC) in DIP induced signal transduction. Down-regulation of PKC by 12-O-tetradecanoylphorbol-13-acetate or addition of CGP 41251, a selective inhibitor of PKC, inhibited beta-casein protein expression induced by DIP in HC11 cells. This inhibition occurs at the level of transcription, since the DIP mediated activation of a beta-casein promoter-luciferase reporter construct or of mammary gland specific factor (MGF), an essential transcription factor for beta-casein promoter activity, was also inhibited by CGP 41251. Inhibition or down-regulation of PKC reduced the activation of MGF by prolactin as well. PKC-alpha, the only conventional PKC isoform expressed in HC11 cells, is most likely involved in the D...