Transferrin is a glycosylated metal-carrying serum protein. One of the biological functions of glycosylation is to regulate the life span of proteins, less glycosylation leading to a faster clearance of a protein from the circulation. In the case of transferrin, this would indirectly also influence iron homeostasis. Higher glycosylation has been demonstrated in patients with Parkinson's disease and rheumatoid arthritis. A genetic variant of transferrin, TfC2, occurs with increased frequency in patients with Alzheimer's disease (AD), rheumatoid arthritis, and other diseases associated with a free radical etiology. Investigations have so far not revealed the reason for the pro-oxidative qualities of TfC2. In this study the glycosylation of Tf in AD (TfC1 homozygotes and TfC1C2 heterozygotes) was compared with alcohol-induced dementia (AID) patients and nondemented, age-matched controls, using isoelectric focusing followed by blotting with anti-Tf antibodies. In TfC1 homozygotes a shift was found toward higher sialylation, but in TfC1C2 heterozygotes the 5- and 6-sialylated bands were less concentrated. The decreased sialalytion found for TfC1C2 heterozygotes, may indicate that the pro-oxidative TfC2 molecules are removed from the circulation at a faster rate than TfC1. This may be of benefit to AD patients having TfC2, but still does not explain why this Tf variant is pro-oxidative.
Dysbiosis of the microbiome is a common finding in critically ill patients, who receive broad-spectrum antibiotics and various forms of organ support. Multidrug-resistant (MDR) organisms are a growing threat in all areas of medicine, but most markedly in the critically ill, where there is both loss of host defences and widespread use of broad spectrum antibiotics. We present a case of a critically ill patient with persistent MDR Klebsiella pneumoniae infection, successfully treated with fecal microbiota transplantation (FMT), using stool of a rigorously-screened, healthy donor. FMT for Clostridium difficile colitis has been well described in the literature and is an established therapy for recurrent infections with Clostridium difficile. The use of FMT for other multidrug-resistant organisms is less frequently described, particularly in the context of critically ill patients. In our case, we have culture-documented clearance of the MDR Klebsiella pneumoniae form a patient of FMT.
e c e m b e r 2 0 0 9 Abacavir (ABC), a nucleoside reverse transcriptase inhibitor (NRTI), combined with lamivudine (3TC), has a better short-and long-term outcome than 3TC combined with zidovudine (ZDV) as first-line HIV therapy. 1,2 In addition, children failing ABC/3TC-based first-line therapy do not select thymidine NRTI-related mutations, allowing for better choice in second-line therapy.2 With current first-line options, both first-line (stavudine (d4T)) and second-line therapy (ZDV) include a thymidine-based NRTI, thus compromising second-line regimens. [3][4][5] In well-selected children, ABC is also an important drug in second-line and salvage therapy. 6Of all the NRTIs, ABC is associated with the lowest rate of mitochondrial dysfunction. Types of dysfunction include lactic acidosis, peripheral neuropathy and lipo-atrophy. Substitution of d4T for ABC improves mitochondrial indices and reduces adipocyte apoptosis. 7 In adults, switching from d4T to ABC was superior to switching from d4T to ZDV. 8 In older children, once-daily use of ABC has also been shown to be effective, thereby facilitating adherence and improving patient satisfaction, particularly when all drugs are given once daily. 9,10Despite these advantages, ABC is rarely used as part of first-line therapy in South Africa owing to cost. Tenofovir, commonly used in adults experiencing NRTI adverse events, is not licensed for children. With large cohorts of children now on antiretroviral therapy for long periods of time, increased use of ABC is likely as NRTI adverse events become apparent. Currently, the National Department of Health permits using ABC when there have been adverse events related to other NRTIs.Of concern is the severe and life-threatening hypersensitivity reaction (HSR) that occasionally occurs, necessitating permanent discontinuation of ABC.ABC HSR has been reported in adults and children. The prevalence in clinical trials varies.11 In a European trial of first-line therapy, where 92 children were initiated on ABC, 4 (4.3%) terminated ABC for adverse reactions, 1 case (1%) being considered an HSR. There is clear heterogeneity in risk according to ethnic groups, with Caucasians at higher risk and a 40% reduction in risk for African Americans. In the ARROW study of >1 200 HIV-infected children in Uganda and Zimbabwe, HSR was reported in 0.2% of the children. 12Other factors that may be protective are male sex and more advanced disease. However, this assessment was performed before identification of the genetic link to HSR. 13 HLA-B*5701 AND HSRAn association with ABC HSR was described with HLA-B*5701, HLA-DR7 and HLA-DQ3. If all three markers are present, the positive predictive value for HSR is 100% with a negative predictive value of 97%. HLA-B*5701 alone is highly predictive. 14 It is clear that the varied distribution of the HLA-B*5701 genotype is responsible for variability of the risk of ABC HSR between races and studies. 15 Studies from the USA indicated that this mutation is more prevalent among white and Hispanic persons t...
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