Pentoxifylline therapy in human immunodeficiency virus-seropositive persons with tuberculosis: a randomized, controlled trial

Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-alpha and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/microL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum beta 2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted.     

Clostridium tertium bacteremia: 2 cases and review

Clostridium tertium bacteremia is unusual, seen most often with gastrointestinal disease and/or neutropenia. Two cases are described. The first was a 19-yr-old female with acute leukemia, who developed gastrointestinal symptoms and C. tertium bacteremia while neutropenic. The second was a 57-yr-old female with quiescent ulcerative colitis, who presented with fever, rigors and epigastric pain. Four organisms including C. tertium were isolated from blood cultures. This patient responded to broad spectrum antimicrobial therapy, whereas the first patient required the addition of specific agents to recover. C. tertium is aerotolerant and thus can be misidentified as a Bacillus or Corynebacterium spp. Our isolates had a distinctive Gram stain morphology, were catalase negative and failed to sporulate aerobically--this aided in the recognition of this significant Gram-positive bacillus.     

Oxidant damage to erythrocyte membrane in glucose-6-phosphate dehydrogenase deficiency: correlation with in vivo reduced glutathione concentration and membrane protein oxidation

Chronic nonspherocytic hemolytic anemia has been observed in a recently described glucose-6-phosphate dehydrogenase (G6PD) variant, G6PDWayne. The mechanical properties of these erythrocytes and other G6PD variants were examined. The deformability of G6PD-deficient erythrocytes was normal, as determined by osmotic scan ektacytometry, and was not significantly affected by hemolytic crisis. In the common varieties of G6PD deficiency, the mechanical stability of the red blood cell (RBC) membrane was greater than normal, but G6PDWayne membranes were abnormally susceptible to shear-induced fragmentation. There was no evidence for a concurrent genetic defect in spectrin, because self-association constants and tryptic digests were normal. The fragility of G6PDWayne membranes appeared to be a consequence of oxidative damage to membrane thiol groups associated with a low glutathione (GSH) level in these RBCs. Associations among GSH level, thiol oxidation, and membrane instability were also found when a larger group of G6PD-deficient RBCs were examined. In normal erythrocytes, 1-chloro-2,4-dinitrobenzene was used to reduce GSH levels by 50%. Membrane thiol oxidation and membrane fragility both increased when these cells were kept at 4 degrees C for 3 to 5 days. Our findings suggest that chronic depletion of GSH leads to the destabilization of membrane skeleton through oxidation of membrane protein thiols.     

Metabolic factors have a major impact on kidney allograft survival

BACKGROUND: At the present time, late graft loss is the major cause of kidney failure after transplantation. However, the influence of metabolic factors on this process is ill-defined. METHODS: To identify the impact of lipid metabolism, glucose metabolism, and blood pressure and their prognostic value for graft survival, data for all recipients of a kidney allograft with a potential graft survival of >15 years and a minimum graft survival of 1 month were analyzed retrospectively. Recipients of kidney grafts functioning more than 15 years (n=32) were compared with those with a graft function of less than 10 years (n=152, controls) and evaluated in a multivariate analysis. RESULTS: Low levels of serum cholesterol, triglycerides, and glucose, before and after transplantation, were accompanied by a prolonged graft survival. Prognostic factors for early graft failure included serum triglycerides >300 mg/dl, cholesterol >250 mg/dl before transplantation, serum creatinine >4.0 mg/dl 1 month after transplantation, and donor age above 45 or less than 10 years. Additionally, systolic and, particularly, diastolic blood pressure was lower in the group with a prolonged graft function as compared with controls immediately before and after transplantation. In addition, the incidence of primary graft function was lower and the incidence of acute rejection episodes higher in controls. Cold and warm ischemic time, body mass index, recipient age, and gender did not differ significantly. CONCLUSIONS: Our data suggest that metabolic parameters play an important role in the process of late graft loss after kidney transplantation.     

News: White House panel creating database of endocrine disrupter-related research

Science.     

News: EPA tries "StarTrack" permits in New England

Government.     

News: EPA report targets 10 key research areas

Science.     

Nanoparticles in Catalysis

In this article, we report studies of two new forms of highly active supported catalysts. First, those derived from supported carbonylate clusters—nanocatalysts and second, those produced from the heterogenization of known chiral homogeneous systems. The utilization of established cluster compounds of precisely known composition and structure have proved invaluable in the preparation of mixed metal nanoparticles of well-defined composition. The attachment of these nanoparticles to the inner walls of mesoporous silica has led to the development of highly active and effective catalysts for a series of hydrogenation reactions, emphasizing the enhanced reactivity of these metal systems as a consequence of their size and of the low coordination numbers of the metal atoms involved. These attributes combined with the relative ease of characterization of both the active sites and their location has led to a detailed examination of the role of these nanosystems in a new approach to clean technology. In an alternative strategy, the use of heterogenized homogeneous chiral catalysts based on the ferrocenyl moiety and diamino ligands and linked to the inner surface of mesoporous materials either by a direct chemical bond or by an ionic interaction has also been explored. These catalysts have been shown to be highly effective in the enantioselective synthesis of organic compounds. Significantly, we have found that the mesopore (usually MCM-41) imposes spatial restrictions arising from the concavity of the inner surface and leads to greatly enhanced enantioselective (ee) performance.