An unusual case of orbital involvement and pan-ocular inflammation in Acute Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. At the onset, SLE may involve only one organ (additional manifestations may occur later) or multiple organs. The ocular manifestations are varied and involve the lids, cornea, sclera and or orbit. There may be associated secondary Sjogren's syndrome, conjunctival haemorrhages, retinal vascular disease with retinal haemorrhages and neuro-ophthalmic lesions. Pan-ophthalmic involvement is rare and sight threatening and requires urgent ophthalmic intervention. We hereby present an unusual case of pan-ophthalmic inflammation in case of acute systemic lupus

Bilateral medial rectus palsy due to midbrain infarction following concussion head injury

Here, we report a rare case of bilateral medial rectus palsy following closed head injury. An adult male had an accidental fall which rendered him unconscious. This was followed by diplopia and restricted ocular motility. He received supportive medical therapy. He was examined for systemic medical and ophthalmic findings. Routine laboratory tests and imaging techniques were employed as per the symptoms. Diffusion-weighted imaging on magnetic resonance imaging proved it to be a rare presentation of small bilateral midbrain infarct. He recovered fully after 8 months

Measurement of the kinetics of protein uptake by proximal tubular cells using an optical biosensor

Measurement of the kinetics of protein uptake by proximal tubular cells using an optical biosensor.BackgroundThe affinity and specificity of protein reabsorption by proximal tubular cells have been investigated using techniques for monitoring endocytosis, demonstrating a high capacity but low affinity process. It is not known whether uptake is through binding to a single binding site/receptor with differing affinities, or if there are several classes of binding sites receptors, each specific for differing proteins or groups, such as, high or low molecular weight proteins.MethodsWe have developed a novel technique for analyzing the kinetics of protein binding to tubular cells using a optical biosensor system. We have studied the binding of cultured LLCPK cells to albumin and RBP immobilized onto the sensor. By adding increasing concentrations of competing proteins [varying in molecular weight from 66,000 to 11,800 D and pI from 4.6 to 9.2 as represented by albumin, alpha1-microglobulin (α1M), retinol binding protein (RBP), cystatin C and beta2-microglobulin (β2m)], specific and inhibitable cell binding was demonstrated.ResultsEquilibrium constants, KA, could be calculated from the reciprocal of the protein concentration causing 50% inhibition in binding rate. These were: albumin = 8.0 × 104m-1, α1M = 2.0 × 105m-1, RBP = 2.7 × 104m-1, cystatin C = 2.0 × 104m-1, β2m = 4.2 × 103m-1. There were no significant differences between the measured KA’s whether RBP or albumin were immobilized on the surface.ConclusionsAll the proteins gave similar shaped inhibition profiles, suggesting that there is one binding site/receptor for all proteins studied, regardless of molecular weight or charge, but there are differing affinities for each protein

Tryptophan–NAD+ pathway metabolites as putative biomarkers and predictors of peroxisome proliferation

The present study was designed to provide further information about the relevance of raised urinary levels of N-methylnicotinamide (NMN), and/or its metabolites N-methyl-4-pyridone-3-carboxamide (4PY) and N-methyl-2-pyridone-3- carboxamide (2PY), to peroxisome proliferation by dosing rats with known peroxisome proliferator-activated receptor α (PPARα) ligands [fenofibrate, diethylhexylphthalate (DEHP) and long-chain fatty acids (LCFA)] and other compounds believed to modulate lipid metabolism via PPARα-independent mechanisms (simvastatin, hydrazine and chlorpromazine). Urinary NMN was correlated with standard markers of peroxisome proliferation and serum lipid parameters with the aim of establishing whether urinary NMN could be used as a biomarker for peroxisome proliferation in the rat. Data from this study were also used to validate a previously constructed multivariate statistical model of peroxisome proliferation (PP) in the rat. The predictive model, based on H nuclear magnetic resonance (NMR) spectroscopy of urine, uses spectral patterns of NMN, 4PY and other endogenous metabolites to predict hepatocellular peroxisome count. Each treatment induced pharmacological (serum lipid) effects characteristic of their class, but only fenofibrate, DEHP and simvastatin increased peroxisome number and raised urinary NMN, 2PY and 4PY, with simvastatin having only a transient effect on the latter. These compounds also reduced mRNA expression for aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase, EC 4.1.1.45), the enzyme believed to be involved in modulating the flux of tryptophan through this pathway, with decreasing order of potency, fenofibrate (-10.39-fold) >DEHP (-3.09-fold) >simvastatin (-1.84-fold). Of the other treatments, only LCFA influenced mRNA expression of ACMSDase (-3.62-fold reduction) and quinolinate phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) (-2.42-fold) without any change in urinary NMN excretion. Although there were no correlations between urinary NMN concentration and serum lipid parameters, NMN did correlate with peroxisome count (r =0.63) and acyl-CoA oxidase activity (r =0.61). These correlations were biased by the large response to fenofibrate compared to the other treatments; nevertheless the data do indicate a relationship between the tryptophan-NAD pathway and PPARα-dependent pathways, making this metabolite a potentially useful biomarker to detect PP. In order to strengthen the observed link between the metabolites associated with the tryptophan-NAD pathway and more accurately predict PP, other urinary metabolites were included in a predictive statistical model. This statistical model was found to predict the observed PP in 26/27 instances using a pre-determined threshold of 2-fold mean control peroxisome count. The model also predicted a time-dependent increase in peroxisome count for the fenofibrate group, which is important when considering the use of such modelling to predict the onset and progression of PP prior to its observation in samples taken at autopsy