Rapidly proliferating CD44hi peripheral T cells undergo apoptosis and delay posttransplantation T-cell reconstitution after allogeneic bone marrow transplantation

Delayed T-cell recovery is an important complication of allogeneic bone marrow transplantation (BMT). We demonstrate in murine models that donor BM-derived T cells display increased apoptosis in recipients of allogeneic BMT with or without GVHD. Although this apoptosis was associated with a loss of Bcl-2 and Bcl-X(L) expression, allogeneic recipients of donor BM deficient in Fas-, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)- or Bax-, or BM-overexpressing Bcl-2 or Akt showed no decrease in apoptosis of peripheral donor-derived T cells. CD44 expression was associated with an increased percentage of BM-derived apoptotic CD4(+) and CD8(+) T cells. Transplantation of RAG-2-eGFP-transgenic BM revealed that proliferating eGFP(lo)CD44(hi) donor BM-derived mature T cells were more likely to undergo to apoptosis than nondivided eGFP(hi)CD44(lo) recent thymic emigrants in the periphery. Finally, experiments using carboxyfluorescein succinimidyl ester-labeled T cells adoptively transferred into irradiated syngeneic hosts revealed that rapid spontaneous proliferation (as opposed to slow homeostatic proliferation) and acquisition of a CD44(hi) phenotype was associated with increased apoptosis in T cells. We conclude that apoptosis of newly generated donor-derived peripheral T cells after an allogeneic BMT contributes to delayed T-cell reconstitution and is associated with CD44 expression and rapid spontaneous proliferation by donor BM-derived T cells.     

The effect of inhaled corticosteroids on bronchoalveolar lavage cells and IL-8 levels in stable COPD patients

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammatory process in the large and small airways, as well as in the lung parenchyma. Although the role of oral corticosteroids in the management of acute exacerbations of COPD is well documented, its role in stable COPD is not clear. We examined the anti-inflammatory effect of inhaled budesonide on the percentage of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL) and their correlation with spirometry and symptom scores. Twenty-six patients with stable COPD were randomised, in a double-blinded, placebo-controlled trial with either 800 microg of inhaled budesonide or placebo for a 6-month period. The budesonide-treated subjects had significant reductions in IL-8 levels in the BAL after therapy (mean+/-sem, 1.53+/-0.72 at baseline vs. 0.70+/-0.48 ng/ml at 6 months, P=0.004) and a reduction in the mean percentages of neutrophils (17.16+/-2.67% vs. 13.25+/-2.28% P=0.002). The improvement in sputum production was of borderline (P=0.058) significance but there was no improvement in lung function. In stable patients with COPD, treatment with inhaled budesonide for a period of 6 months has a positive effect on markers of lung inflammation, as assessed by reduction in percentage neutrophils and IL-8 concentration in BAL.     

TNF-alpha antagonist therapy modify the tuberculin skin test response

Tumour necrosis factor-alpha (TNF-α) antagonist drugs have been associated with increased risk of tuberculosis (TB). Tuberculin skin test (TST) is the most frequently used tool for identification of latent TB infection. We herein aimed to analyse the effect of TNF-α antagonists on the TST responses in a prospective study. The study group consisted of 182 patients (99 female, 83 male) who received TNF-α antagonists for various rheumatic disorders. All patients were evaluated with TST along with other parameters on the day of referral and on the 12th month visit. For those patients with a response of <5 mm induration at the initial evaluation, the TST was repeated to observe the booster effect. Out of 182 patients, 87 patients (48%) had a negative (0–4 mm) and 95 (52%) had a positive (≥5 mm) TST response at initial evaluation. The TST responses were converted from negative at initial visit to positive at 1-year repeat in 26 (30%) patients. A significant increase was observed in the diameters of TST that were repeated on the first year of TNF-α antagonist treatment (9.15 ± 0.55) compared to their initial diameters (6.60 ± 0.51) (P < 0.001). Increased TST responses in patients receiving TNF-α antagonists may be associated with the restoration of suppressed immune reactivity against TB antigens with the decreased disease activity. The meaning of TST conversion in the definition of latent TB infection and the need for chemoprophylaxis in these patients remains to be answered by further studies.     

Effects of nicorandil on renal function and histopathology in rats with partial unilateral ureteral obstruction

To evaluate the effects of nicorandil in a rat kidney model of partial unilateral ureteral obstruction (PUUO). Thirty male rats were randomly divided into three groups as follows: (1) Group 1 (Sham-control), ureters of the rats were manipulated but not ligated; (2) Group 2 (PUUO-untreated), PUUO was performed with two-thirds of the left ureter embedded in the psoas muscle; and (3) Group 3 (PUUO-nicorandil treated). After PUUO was established, nicorandil (15 mg/kg/day) was administered by gastric lavage for 21 days to determine its effects on PUUO-induced histopathological-, functional-, and oxidative stress-induced changes. The serum levels of blood urea nitrogen and creatinine were reduced in Group 3. The level of urinary albumin and the ratio of urinary protein/creatinine were increased in the kidneys of Group 2 but decreased in Group 3. Malondialdehyde value was decreased in Group 3 compared with Group 2. Antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) were decreased in Group 2. Nicorandil treatment caused an increase in these enzyme activities. In Group 3, leukocyte infiltration and tubular dilatation were significantly reduced. Other parameters, such as degeneration of tubular epithelium and fibrosis, also showed a marked improvement in Group 3. Expression of inducible nitric oxide synthase in Group 2 and expression of endothelial nitric oxide synthase in Group 3 were significantly elevated. Nicorandil can inhibit renal tubular damage and tubulointerstitial fibrosis by reducing the effects of oxidative stress after PUUO.     

Copeptin and cardiovascular disease: A review of a novel neurohormone

Neurohormones (NHs) in the cascade of the arginine vasopressin (AVP) system have drawn particular attention in the recent years. Copeptin, the C-terminal portion of provasopressin, is a novel NH of the AVP system, and is known to be co-released with AVP from hypothalamus (neurohypophysis). As a surrogate marker of the AVP system, copeptin has gradually replaced AVP in several clinical studies largely due to its structural and methodological advantages. Copeptin has been regarded as a marker of non-specific stress response, and has also been suggested to have clinical implications in a variety of non-cardiovascular (pneumonia, sepsis, etc.) and cardiovascular conditions (heart failure and acute coronary syndromes (ACSs, etc.)). However, current data on relation of copeptin with other cardiovascular conditions ( arrhythmias, etc.) are still insufficient. The present review primarily focuses on general features of copeptin, its general clinical implications, and specifically aims to cover its potential clinical value in a variety of cardiovascular conditions.     

Changes on the Pancreas in Experimental Diabetes and the Effect of Lycopene on These Changes: Pdx‐1, Ngn‐3, and Nestin Expressions

The aim of the present study was to investigate changes occurring in the number of beta cells, as well as the expressions of Ngn‐3, nestin and Pdx‐1 of pancreatic progenitor cells in the pancreas of experimentally‐induced adult diabetic rats and to determine the effect of orally‐administered lycopene on these changes. Following the administration of 50 mg/kg streptozotocin to rats, four groups of animals were established: control + corn oil, control + lycopene, diabetic + corn oil and diabetic + lycopene. The animals in the control + lycopene and diabetic + lycopene groups received 4 mg/kg lycopene for a period of four weeks. The expressions of insulin, Ngn‐3, nestin, and Pdx‐1 were determined through immunohistochemistry in sections taken from pancreas tissue samples at the end of the experiment. The number of insulin‐positive cells was found to be significantly low in the diabetic groups compared to the control groups. In addition, the presence of Ngn‐3 and nestin‐positive cells within the exocrine pancreas surrounding the islands was noted in the diabetic groups. Lycopene, in general did not have any effect in any of the parameters analyzed in the present study. It is suggested that these cells would function as stem cells to replace the lost beta‐cell population. It is also suggested that it is possible to demonstrate the antioxidant effects of lycopene in the pancreas of diabetic rats by increasing the dose and duration of lycopene administration. Anat Rec, 300:2200–2207, 2017. © 2017 Wiley Periodicals, Inc.     

Unique duodenal hamartomatous polyp--case report

Duodenal tumors are very rare tumors, with the lower incidence among the tumors of the small bowel, whose frequence is less than 5 % of all digestive tumors. In most of the cases these tumors remain asymptomatic, sometimes the entire life. When they become symptomatic, their first manifestation is the loss of digested blood (melena), secondary anemia and obstructive symptomatology. Early diagnosis of these tumors is difficult because of the unsystematic symptomatology and becomes easy when the complications appear. In most of the cases the diagnosis is establish by the superior digestive endoscopy, followed by barium contrast studies, CT and ultrasound. We present a case of duodenal hamartomatous polip, unique, at the level of D3, in a female patient 66 years old, addressing to our service for superior digestive hemorrhage exteriorizated by melena, secondary anemia and physical asthenia; we operated the patient procedeeing a polypectomy by a duodenotomy.     

Pure yolk-sac tumor of the lung

Primary germ cell tumors of the chest often localize in the anterior mediastinal compartment. Such tumors originating from lungs and pleura are rare. Chest tomography revealed a mass in the middle lobe of the right lung in a 25-year-old man. A middle lobe medial segmentectomy was performed, and chemotherapy was applied postoperatively.     

Successful medical treatment of intracranial abscess caused by Brucella spp

An unusual presentation of unilateral cerebellar abscesses due to neurobrucellosis observed in a patient is reported. He gave a history of fever, headache, vomiting and had unilateral cerebellar signs. The abscess was detected on magnetic resonance imaging (MRI) and analysis of cerebrospinal fluid revealed neurobrucellosis. Patient treated by only antibiotics therapy, evolving to complete clinical and radiological resolution, without neurosurgical intervention. We are presenting a case of cerebellar abscess due to neurobrucellosis diagnosed by MRI, treated medically, and had both radiologic and clinical follow-up. We also made a review of the literature concerning the cerebellar abscess due to neurobrucellosis.