Increased free malondialdehyde concentrations in smokers normalise with a mixed fruit and vegetable juice concentrate: a pilot study.

Background: Cigarette smoking, a cardiovascular risk factor leading to oxygen free radical formation, is involved in the development of serious pathological conditions. On the other hand, a healthy diet and adequate supplementation can help prevent many diseases. The aim of our study was to evaluate in healthy light smokers the effects of supplementation with mixed fruit and vegetable juice powder concentrate on homocysteine metabolism and oxidative status. Methods: In this pilot study, 32 healthy volunteers, 16 light smokers and 16 non-smokers, on twice daily supplementation were monitored at time zero and after 30 days. Plasma homocysteine, and serum vitamin B(12) and folate concentrations were measured by immunoenzymatic assays; reactive oxygen species, total antioxidant capacity and thiol groups by spectrophotometric methods; and total and free malondialdehyde concentrations by gas chromatography-mass spectrometry with isotopic dilution. Results: Baseline free malondialdehyde concentrations were significantly higher in smokers than in non-smokers and normalised after 30-day supplementation. Baseline results for all the other parameters remained unchanged after supplementation, with no significant differences between smokers and non-smokers. Conclusion: This is the first study showing a significant decrease in free malondialdehyde levels in light smokers after 1-month phytonutrient supplementation.     

N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. II. Evidence for functional cooperation and for coexistence on the same axon terminal.

The possible interactions between activation of N-methyl-D-aspartic acid (NMDA) receptors and non-NMDA receptors regulating the release of [3H]norepinephrine [( 3H]NE) have been investigated in superfused synaptosomes from rat hippocampus. NMDA--at a concentration (100 microM) which, in a medium containing 1.2 mM Mg++ ions, did not evoke [3H]NE release--acquired releasing activity in the presence of equimolar concentrations of quisqualic acid (QA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid. The [3H] NE release evoked by NMDA plus QA in the presence of Mg++ ions was Ca(++)-dependent, partly tetrodotoxin-sensitive, inhibited by clonidine but insensitive to desipramine. The NMDA receptor antagonists D-2-amino-5-phosphonopentanoic acid (D-AP5) and (+)-5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cycloepten-5,10-imine (MK-801) antagonized the NMDA-induced [3H]NE release in Mg(++)-free medium; the IC50 values amounted, respectively, to 81.4 microM and to 1.11 microM. When NMDA was tested in the presence of QA and Mg++ ions, the affinity of D-AP5 was enormously increased (IC50 = 40 nM; i.e., more than 6 orders of magnitude); the affinity of MK-801 was found to be augmented by 350-fold.(ABSTRACT TRUNCATED AT 250 WORDS)     

Competitive engraftment of hematopoietic stem cells genetically modified with a truncated erythropoietin receptor

Transplantation of genetically modified hematopoietic stem cells (HSCs) has therapeutic potential for a variety of blood genetic disorders. Engraftment of HSCs, however, requires toxic myeloablative treatments, which render this approach questionable for non-life-threatening disorders. A potential alternative is the use of transgenes, which allows positive selection of HSCs in vivo. We used retroviral vectors to express a truncated derivative of the erythropoietin receptor (tEpoR) in murine and human hematopoietic cells. Murine HSCs expressing tEpoR at different levels (1500 to 13,000 receptors/cell) acquire a competitive repopulation capacity in vivo upon transplantation into fully or partially myeloablated co-isogenic mouse recipients. Long-term analysis of transplanted mice showed that expression of tEpoR at paraphysiological levels (approximately 1500 receptors/cell) has no effect on steady-state hematopoiesis and induces no further expansion of transduced cells after the engraftment period. Human cord blood-derived CD34+ stem/progenitor cells transduced with a lentiviral vector expressing tEpoR expand their clonogenic capacity in vitro, and significantly increase their marrow repopulation capacity upon xenotransplantation into sublethally irradiated NOD-SCID mice, with no alteration in their phenotype, survival, and differentiation properties. These data indicate that expression of tEpoR is an effective strategy to promote selective engraftment of genetically modified HSCs upon transplantation in both myeloablative and nonmyeloablative conditions, without the use of toxic drugs for selection.     

Incidence and clinical predictors of primary opportunistic deep cutaneous mycoses in solid organ transplant recipients: a multicenter cohort study

Tessari G, Naldi L, Piaserico S, Boschiero L, Nacchia F, Forni A, Rugiu C, Faggian G, Dall’Olio E, Fortina AB, Alaibac M, Sassi F, Gotti E, Fiocchi R, Fagioli S, Girolomoni G. Incidence and clinical predictors of primary opportunistic deep cutaneous mycoses in solid organ transplant recipients: a multicenter cohort study.
Clin Transplant 2010: 24: 328–333. © 2009 John Wiley & Sons A/S. Abstract: Background: Primary opportunistic deep cutaneous fungal
infections may cause significant morbidity and mortality in solid organ transplant recipients (OTR), but no data exist about their incidence, timing, and clinical predictors in a long‐term follow‐up. Patients and methods: A series of 3293 consecutive OTR including 1991 kidney, 929 heart, and 373 liver transplant recipients were enrolled. Patients were regularly followed up since time at transplantation (mean 5.5 yr ±5.9 SD) and primary opportunistic fungal infections registered. Persons‐year at risk (PYs), incidence rates (IR), incidence rate ratios (IRR), and 95% confidence intervals were computed. Results: Twenty‐two cases of deep cutaneous mycoses were detected, (IR 1.2 cases per 1000 PYs) after a mean follow‐up time since transplantation of 2.5 yr ± 2.0 SD (median 1.8 yr). Six patients had subsequent systemic involvement and three patients died of systemic dissemination. A higher risk for mycoses was observed in the first two yr after transplantation, (IRR 35.9, p < 0.0001), in renal transplant recipients (IRR 5.1 p = 0.030), and in patients transplanted after the age of 50 (IRR 11.5 p = 0.020). Conclusions: Primary deep cutaneous opportunistic mycoses in OTR occur mainly in the first two yr after transplantation, in renal transplant recipients, and in older patients.     

Wegener’s granulomatosis presenting with life-threatening lung hemorrhage in a 7-year-old child

Wegener’s granulomatosis (WG) is an idiopathic systemic disease that usually onsets in adolescence and is rare in young children. Its diagnosis is usually based on the presence of fever with arthralgia and weight loss, associated with symptoms of upper and/or lower respiratory tract involvement and renal disorders. We describe the appearance of a life-threatening lung hemorrhage in the absence of hemoptysis in a 7-year-old girl with a completely negative previous clinical history, who was subsequently diagnosed as having WG. The teaching message is that immediate bronchoscopy with bronchoalveolar lavage seems to be advisable in the presence of severe respiratory distress and bilateral lung as well as renal involvement. When a diffuse alveolar hemorrhage syndrome is demonstrated, WG should be considered among the main etiologies even in a relatively young child without a clinically suggestive history.     

Adult T-cell leukemia/lymphoma with Epstein-Barr virus-positive Hodgkin-like cells

Hodgkin-like cells have been described in a variety of non-Hodgkin lymphomas including chronic lymphocytic leukemia and peripheral T-cell lymphoma. There have been rare reports in the Japanese population of human T-cell lymphotrophic virus-1-associated adult T-cell leukemia/lymphoma harboring Hodgkin-like cells; however, no similar cases have been described in Western patients. We report a 53-year-old African American man who presented with progressive weakness and lethargy, and was found to have generalized lymphadenopathy and hypercalcemia. A lymph node biopsy showed involvement by adult T-cell leukemia/lymphoma with scattered Epstein-Barr virus-positive cells, some of which resembled Hodgkin cells that had a B-cell phenotype, consistent with an Epstein-Barr virus-lymphoproliferative disorder. The patient had stage 4 disease with bone marrow involvement. In light of the associated B-cell lymphoproliferative process, the patient was treated with 6 cycles of intensive chemotherapy that targeted both the adult T-cell leukemia/lymphoma and the Epstein-Barr virus-lymphoproliferative disorder that resulted in a complete response. An awareness of the association of Epstein-Barr virus-lymphoproliferative disorder with Hodgkin-like cells in the context of adult T-cell leukemia/lymphoma is necessary to avoid potential misdiagnosis and to aid in therapeutic decisions.     

Phosphodiesterase type IV inhibition prevents sequestration of CREB binding protein, protects striatal parvalbumin interneurons and rescues motor deficits in the R6/2 mouse model of Huntington's disease

The phosphodiesterase type IV inhibitor rolipram increases cAMP response element-binding protein (CREB) phosphorylation and exerts neuroprotective effects in both the quinolinic acid rat model of Huntington's disease ( DeMarch et al. , 2007 ) and the R6/2 mouse including sparing of striatal neurons, prevention of neuronal intranuclear inclusion formation and attenuation of microglial reaction ( DeMarch et al. , 2008 ). In this study, we sought to determine if rolipram has a beneficial role in the altered distribution of CREB binding protein in striatal spiny neurons and in the motor impairments shown by R6/2 mutants. Moreover, we investigated whether rolipram treatment altered the degeneration of parvalbuminergic interneurons typical of Huntington's disease ( Fusco et al. , 1999 ). Transgenic mice and their wild-type controls from a stable colony maintained in our laboratory were treated with rolipram (1.5 mg/kg) or saline daily starting from 4 weeks of age. The cellular distribution of CREB binding protein in striatal spiny neurons was assessed by immunofluorescence, whereas parvalbuminergic neuron degeneration was evaluated by cell counts of immunohistochemically labeled tissue. Motor coordination and motor activity were also examined. We found that rolipram was effective in preventing CREB binding protein sequestration into striatal neuronal intranuclear inclusions, sparing parvalbuminergic interneurons of R6/2 mice, and rescuing their motor coordination and motor activity deficits. Our findings demonstrate the possibility of reversing pharmacologically the behavioral and neuropathological abnormalities of symptomatic R6/2 mice and underline the potential therapeutic value of phosphodiesterase type IV inhibitors in Huntington's disease.