Indolent T-Cell Lymphoproliferative Disease: A Rare Case of a Benign Lymphoma of the Gastrointestinal Tract With Extra-Gastrointestinal Involvement.

Indolent T-cell lymphoproliferative disease of the gastrointestinal (GI) tract is an exceedingly rare benign proliferation of clonal and mature-appearing lymphoid cells originating from the GI tract. We discuss the case of a 52-year-old woman with indolent T-cell lymphoproliferative disease of the GI tract manifesting as chronic diarrhea and profound weight loss. Interestingly, the patient also had extra-GI involvement of her disease process, which has not been previously reported. Our patient was managed with steroids with improvement in symptoms and weight gain. We provide a review of the literature to highlight the importance of early recognition and intervention of this disease entity.

GI Hemorrhage From an Arterio-Enteric Fistula From a Failed Pancreas Allograft.

Arterio-enteric fistulas involving pancreas allograft are rare complications of transplantation that manifest as gastrointestinal bleeding. We discuss the case of a 34-year-old patient with failed pancreas transplant who presented with recurrent sentinel bleeding before catastrophic hemorrhage. Multiple endoscopies did not identify the source of bleeding, and subsequent angiography demonstrated a fistulous connection between the transplanted pancreatic artery and the small bowel. A stent graft was placed with immediate stabilization. We provide a review of the literature and discuss the clinical manifestations, diagnosis, and management of arterio-enteric fistulas to highlight the importance of early recognition and intervention in preventing life-threatening bleeding.

Characterization of a protozoan Phosducin-like protein-3 (PhLP-3) reveals conserved redox activity.

We recently identified three novel thioredoxin-like genes in the genome of the protozoan parasite Plasmodium that belong to the Phosducin-like family of proteins (PhLP). PhLPs are small cytosolic proteins hypothesized to function in G-protein signaling and protein folding. Although PhLPs are highly conserved in eukaryotes from yeast to mammals, only a few representatives have been experimentally characterized to date. In addition, while PhLPs contain a thioredoxin domain, they lack a CXXC motif, a strong indicator for redox activity, and it is unclear whether members of the PhLP family are enzymatically active. Here, we describe PbPhLP-3 as the first phosducin-like protein of a protozoan organism, Plasmodium berghei. Initial transcription analysis revealed continuous low-level expression of pbphlp-3 throughout the complex Plasmodium life cycle. Attempts to knockout pbphlp-3 in P. berghei did not yield live parasites, suggesting an essential role for the gene in Plasmodium. We cloned, expressed and purified PbPhLP-3 and determined that the recombinant protein is redox active in vitro in a thioredoxin-coupled redox assay. It also has the capacity to reduce the organic compound tert-Butyl hydroperoxide (TBHP) in vitro, albeit at low efficiency. Sequence analysis, structural modeling, and site-directed mutagenesis revealed a conserved cysteine in the thioredoxin domain to be the redox active residue. Lastly, we provide evidence that recombinant human PhLP-3 exhibits redox activity similar to that of PbPhLP-3 and suggest that redox activity may be conserved in PhLP-3 homologs of other species. Our data provide new insight into the function of PhLP-3, which is hypothesized to act as co-chaperones in the folding and regulation of cytoskeletal proteins. We discuss the potential implications of PhLP-3 as a thioredoxin-target protein and possible links between the cellular redox network and the eukaryotic protein folding machinery.

The potential application of European market research data in dietary exposure modelling of food additives.

Consumer exposure assessments for food additives are incomplete without information about the proportions of foods in each authorised category that contain the additive. Such information has been difficult to obtain but the Mintel Global New Products Database (GNPD) provides information about product launches across Europe over the past 20 years. These data can be searched to identify products with specific additives listed on product labels and the numbers compared with total product launches for food and drink categories in the same database to determine the frequency of occurrence. There are uncertainties associated with the data but these can be managed by adopting a cautious and conservative approach. GNPD data can be mapped with authorised food categories and with food descriptions used in the EFSA Comprehensive European Food Consumption Surveys Database for exposure modelling. The data, when presented as percent occurrence, could be incorporated into the EFSA ANS Panel's 'brand-loyal/non-brand loyal exposure model in a quantitative way. Case studies of preservative, antioxidant, colour and sweetener additives showed that the impact of including occurrence data is greatest in the non-brand loyal scenario. Recommendations for future research include identifying occurrence data for alcoholic beverages, linking regulatory food codes, FoodEx and GNPD product descriptions, developing the use of occurrence data for carry-over foods and improving understanding of brand loyalty in consumer exposure models.

Molecular cloning, characterization and expression profile of a glutathione peroxidase-like thioredoxin peroxidase (TPxGl) of the rodent malaria parasite Plasmodium berghei.

Glutathione peroxidases (GPx) comprise an important group of redox active proteins with diverse functions, including antioxidant defense and signaling. Although the genome of the malaria parasite Plasmodium does not contain a genuine GPx gene a glutathione peroxidase-like thioredoxin peroxidase (TPx(Gl)) has recently been identified and biochemically characterized in the human malaria parasite P. falciparum. To gain more insight into the potential biological function of this enzyme we have cloned and expressed TPx(Gl) of the rodent model system P. berghei (PbTPx(Gl)). Biochemical characterization confirmed that the protein is redox active with the P. berghei thioredoxin system. We compared PbTPx(Gl) to recently characterized thioredoxin-dependent GPx-type proteins of other organisms, and generated the first hypothetical 3D model of a Plasmodium TPx(Gl), which shows the conservation of the thioredoxin-fold as well as the spatial orientation of a classic GPx catalytic tetrad. In vivo studies indicate that PbTPx(Gl) is continuously expressed in all P. berghei asexual blood stages, gametocytes and in early mosquito-stage parasites. Confocal microscopy suggest a cytoplasmic localization of PbTPx(Gl) in all investigated parasite life stages, specifically in mature ookinetes. Our data provides new insights into the structure and ubiquitous expression of Plasmodium TPx(Gl) and warrants further investigation into this potentially important redox enzyme.

Corneal staining and subjective symptoms with multipurpose solutions as a function of time.

PURPOSE: Short-term changes in corneal staining and ocular symptoms were assessed at defined intervals to evaluate combinations of three soft lenses and four multipurpose solutions. METHODS: A series of pilot studies were conducted over 11 months using a double-masked, randomized, crossover design. Asymptomatic, adapted, daily-wear soft lens users wore group II or IV soft hydrophilic or silicone hydrogel lenses for a maximum period each day. Before wear, new lenses were soaked overnight in one of four multipurpose solutions: Alcon OPTI-FREE Express MPDS, Bausch & Lomb ReNu MultiPlus Multipurpose Solution, CIBA Vision SOLO-Care PLUS Multipurpose Solution, or AMO Complete MoisturePLUS. Subjects rated comfort and ocular symptoms. Corneal staining type and area were evaluated at baseline and after lens removal. RESULTS: Significantly increased extent of corneal staining, defined as the proportion of corneal zones showing staining of grade 1 or more severe, was observed at 1 and 2 hours when subjects wore group II lenses soaked in the polyhexamethylene biguanide-based systems. Significantly increased extent of staining was observed at 2 hours when subjects used silicone hydrogel lenses soaked in regimen 4. When subjects used regimen 1 and wore group II lenses, only a minimal staining response was observed at 1 and 2 hours of wear. Significant symptoms were not correlated with extent of staining. CONCLUSIONS: This study design is a promising tool that can discriminate between the performance of different soft lens and multipurpose solution combinations rapidly using small patient samples. With some lens-care product combinations, corneal appearance may vary according to the time of day the patient is examined.

Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux.

OBJECTIVE: To assess the efficacy of omeprazole in treating irritable infants with gastroesophageal reflux and/or esophagitis. STUDY DESIGN: Irritable infants (n=30) 3 to 12 months of age met the entry criteria of esophageal acid exposure >5% (n=22) and/or abnormal esophageal histology (n=15). They completed a 4-week, randomized, double-blind, placebo-controlled crossover trial of omeprazole. Cry/fuss diary (minutes/24 hours) and a visual analogue scale of infant irritability as judged by parental impression were obtained at baseline and the end of each 2-week treatment period. RESULTS: The reflux index fell significantly during omeprazole treatment compared with placebo (-8.9%+/-5.6%, -1.9%+/-2.0%, P<.001). Cry/fuss time decreased from baseline (267+/-119), regardless of treatment sequence (period 1, 203+/-99, P<.04; period 2, 188+/-121, P<.008). Visual analogue score decreased from baseline to period 2 (6.8+/-1.6, 4.8+/-2.9, P=.008). There was no significant difference for both outcome measures while taking either omeprazole or placebo. CONCLUSIONS: Compared with placebo, omeprazole significantly reduced esophageal acid exposure but not irritability. Irritability improved with time, regardless of treatment.