The inherited 5-oxoprolinuria is primarily suggestive of genetic defects in two enzymes belonging to the gamma-glutamyl cycle in the glutathione (GSH) metabolism: the glutathione synthetase (GSS) and the 5-oxoprolinase (OPLAH). The GSS deficiency is the best characterized of the inborn errors of GSH metabolism, whereas the OPLAH deficiency is questioned whether it is a disorder or just a bioche...

Cigarette smoke contains numerous oxygen free radicals that when inhaled, overwhelm antioxidant defenses and produce a condition of oxidative stress. This study investigated whether or not supplementation with vitamin E can affect the state of oxidative stress in healthy smokers. In this randomised double blind trial, 32 smokers received 200 mg of vitamin E or placebo daily for 8 weeks. All smo...

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH pat...

5-Oxoprolinuria is a recognized condition with increased urinary excretion of 5-oxoproline and is associated with a variety of inborn metabolic defects involving the series of enzyme-linked reactions known as the gamma-glutamyl cycle. We report the unusual case of a 35-year-old woman who initially presented with staphylococcal pneumonia but went on to develop a transient high anion gap metaboli...

Patients with hereditary glutathione synthetase deficiency suffer from haemolytic anaemia, 5-oxoprolinuria, metabolic acidosis, recurrent bacterial infections and various degrees of central nervous system dysfunction. To investigate the molecular basis of the mutations associated with this disease, seven naturally occurring missense mutations [L188P (Leu188-->Pro), D219A, D219G, Y270C, Y270H, R...

The clinical and laboratory features of a 3-mo-old black male infant with glutathione (GSH) synthetase deficiency of the generalized type was evaluated. Partial albinism, brisk hemolytic anemia, recurrent febrile episodes, and mental retardation were noted. Also, severe recurrent metabolic acidosis and marked oxoprolinemia and oxoprolinuria were found in the proband but not in his first-degree ...

Glutathione synthetase (GS) catalyses the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. Malfunctioning of GS results in disorders including metabolic acidosis, 5-oxoprolinuria, neurological dysfunction, haemolytic anaemia and in some cases is probably lethal. Here we report the crystal structure of human GS (hGS) at 2.1 A resolution in complex wit...

We report the application of pump-probe fluorescence microscopy in time-resolved polarization imaging. We derived the equations governing the pump-probe stimulated emission process and characterized the pump and probe laser power levels for signal saturation. Our emphasis is to use this novel methodology to image polarization properties of fluorophores across entire cells. As a feasibility stud...

It has been demonstrated that Holarrhena antidysenterica Wall. (Apocynaceae) is useful as an adjunctive therapy for Inflammatory bowel disease (IBD). However, its effect on ulcerative colitis has not been investigated. In the present study, Holarrhena antidysenterica was tested for 2, 4 dinitro benzene sulfonic acid (DNBS) induced colitis, and antioxidant activity was evaluated to clarify its p...

Contact allergy to environmental xenobiotics is a common and important problem, but it is unclear why some chemicals are potent sensitizers and others weak/nonsensitizers. We explored this by investigating why similar chemicals, 2,4-dinitrochlorobenzene (DNCB) and 2,4-dinitrothiocyanobenzene (DNTB), differ in their ability to induce contact hypersensitivity (CHS). DNCB induced CHS in humans, wh...