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Immunosuppression after transplantation renders the transplant recipient susceptible to a broad array of viral pathogens. Of 31 patients transplanted during 2012 in our center, 6 (19.3%) experienced varicella zoster virus (VZV) reactivation. The median time from transplantation to reactivation was 6.2 months. Immunosuppression consisted of antithymocyte globulin in 5 patients and basiliximab in 1, followed by tacrolimus, mycophenolic acid, and prednisolone. Two patients had T-cell–mediated rejection and were treated with pulse doses of corticosteroids. All patients received valganciclovir as prophylaxis of CMV infection. In 3 patients a disseminated vesicular skin rash was the sole manifestation of VZV reactivation. Two were successfully treated with acyclovir and 1 with ganciclovir. Ramsay Hunt syndrome complicated herpes zoster in the fourth patient, whereas the remaining 2 patients had visceral involvement, pneumonitis, and encephalitis, and died in spite of full doses of antiviral therapy. This was the first case of “epidemic” VZV reactivation in the 35-year history of our transplant center. VZV-specific cellular immunity pretransplantation is not sufficient to protect kidney transplant recipients from herpes zoster episodes. Considering the potentially devastating consequences of VZV reactivation, additional treatment options and universal prophylaxis should be contemplated. [ABSTRACT FROM AUTHOR]

BALB/c mice are resistant to diabetes induced by multiple low doses of streptozotocin (MLD-STZ; 5 × 40 mg/kg body weight [b.w.]) regimen in contrast to C57/BL6 mice. The deletion of ST2 gene renders BALB/c mice susceptible to diabetes induction. Cyclophosphamide (CY) in the dose of 175 mg/kg b.w. eliminated CD4+Foxp3+ regulatory T cells (Tregs) and enhanced disease severity in C57/BL6 mice, but it did not overcome resistance to diabetes in BALB/c mice and did not affect diabetes progression in ST2 knock-out (ST2KO) mice. We argued that a lower dose of CY may selectively eliminate Tregs while sparing effector T cells in BALB/c mice. Indeed, only a very low dose of CY (50 mg/kg b.w.) enhanced diabetes severity in ST2KO mice. This treatment eliminated Tregs in pancreatic lymph nodes in ST2KO mice, while markedly increasing the influx of CD8+, CD4+TNF-α+, and CD4+IFN-γ+ effector T cells (Teffs) in pancreata. Also, the aggravation of diabetes was accompanied with increased serum levels of TNF-α, IFN-γ, and IL-17. Taken together, our data suggest that the prevailing Th2 immune response in BALB/c mice may be responsible for the resistance to MLD-STZ diabetes and that ST2 gene deletion reveals the role of highly cyclophosphamide sensitive CD4+Foxp3+ regulatory T cells in the pancreatic lymph nodes in diabetes modulation. [ABSTRACT FROM AUTHOR]

Abstract: The causes of neurodegeneration are not well understood. However, the role of environmental and endogenous toxins is receiving much attention. In this study, we compared the synthetic neurotoxin 1-methyl-4-phenyl-pyridinium with β-carbolines occurring in human brain. Methylation of both nitrogens is necessary to convert a β-carboline into a potent inhibitor of mitochondrial complex I. The respective β-carboline, 2,9-dimethyl-β-carbolinium ion is neurotoxic in rats. To investigate the underlying mechanisms, we incubated mouse neuroblastoma 2A cells with 2,9-dimethyl-β-carbolinium ion, and compared the findings with effects of norharman, the precursor β-carboline of methylated derivatives, and with 1-methyl-4-phenyl-pyridinium. 2,9-Dimethyl-β-carbolinium ion caused a significant increase of reactive oxygen species (higher efficiency than 1-methyl-4-phenyl-pyridinium) and of mitochondrial membrane potential within the first minutes. After 60 min, the membrane potential dissipated. Concomitantly, the levels of glutathione increased in 2,9-dimethyl-β-carbolinium ion but not in 1-methyl-4-phenyl-pyridinium treated cells. After 24 h effector caspases 3 and 7 were activated and the number of apoptotic cells increased as revealed by fluorescence-activated cell sorting cytometry. When incubated longer (48 h), cells underwent late apoptosis/secondary necrosis as shown by fluorescence-activated cell sorting analysis and confirmed qualitatively by an electron microscopy study. The effects of 2,9-dimethyl-β-carbolinium ion on apoptotic changes were similar to those induced by 1-methyl-4-phenyl-pyridinium, while norharman showed only a weak potency at the very high doses. To investigate whether 2,9-dimethyl-β-carbolinium ion is neurotoxic under in vivo conditions and whether only dopaminergic neurones are affected we conducted a dose-response study. Three weeks after injection of 2,9-dimethyl-β-carbolinium ion in the substantia nigra we found a dose-dependent decrease of dopamine and its metabolites in the striatum of rats. The levels of 5-hydroxytryptamine were diminished although the decrease was less. The levels of noradrenaline increased after some doses. The findings strongly suggest an important role of endogenous β-carbolines in neurodegeneration with apoptosis as the predominant mechanism. [Copyright &y& Elsevier]

The natural β-carbolines (BC) closely resemble the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in structure. The N-methylated β-carbolinium ions (BC+) are potent inhibitors of mitochondrial respiration and are nigrostriatal neurotoxins. Utilizing [3H]BC, we have identified several proteins to which BC binds with high affinity (e.g. the chaperone member glucose regulated protein 78, the enzyme carboxylesterase, the cytochrome P450 2E1, the enzyme monoamine oxidase B and a small G-protein of the Rho subfamily). In the present study we isolated a protein from bovine brain to which [3H]BC binds with high affinity and identified it being the enzyme triosephosphate isomerase (TPI; EC 5.3.1.1.). 2,9-Dimethyl-BC+ was the most potent inhibitor of TPI, clearly more potent than the known inhibitors. TPI deficiency is a rare disorder in humans characterized by a severe progressive extrapyramidal course. Thus, TPI inhibition could contribute to neurodegeneration observed after injection of BCs into substantia nigra. Furthermore, the findings fit into the hypothesis of BCs as endogenous toxins responsible for neurodegeneration. [Copyright &y& Elsevier]

The depressant effect of corn starch, its polysaccharide components (amylose and amylopectin), the monomer glucose and the dimer maltose were studied on hematite and quartz, by means of infrared spectrometry, adsorption isotherms determination and microflotation tests. All the carbohydrates tested have been effective in maintaining hematite hydrophilic, including glucose and maltose; as for quartz, only a flocculation action (mainly by amylopectin) had a mild effect in decreasing its floatability by the amine collector. FTIR studies confirmed that the carbohydrates adsorbed intensively onto hematite and the spectra of the adsorbed polymers and monomer were very similar, even though the non-adsorbed monomer spectrum was markedly different. The common adsorption mechanism indicated is a surface reaction involving the iron ion. [Copyright &y& Elsevier]

Abstract: An atypical case of Philadelphia (Ph) negative, e1a2 BCR–ABL transcript positive chronic myeloid leukemia (CML) characterized with cyclic periodic leukocytosis and spontaneous remissions is reported. The patient was treated with imatinib and good hematology response with molecular remission was achieved. So far, only few Ph positive CML patients expressing p190 BCR–ABL protein and different clinical characteristics and treatment have been described in the literature. This is the first report of Philadelphia negative, p190 BCR–ABL positive CML with cyclic spontaneous oscillation of white blood cell count (WBC), and excellent response to imatinib treatment. [Copyright &y& Elsevier]