Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031117 (peripheral neuropathy)
 10,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 60-year-old man presented to the Emergency Department (ED) with large, painful, indurated plaques on the right thigh, left abdomen, left chest, and right chest, which began without any preceding trauma on the right thigh 3 weeks prior to presentation in the ED. He was initially treated with cefazolin 1 g three times daily as home infusions. When the lesions continued to progress, he was admitted to the hospital and placed on amoxicillin/clavulanate and vancomycin. He had a single episode of fever of 102 degrees F, but his white blood cell count and differential remained normal. An initial biopsy showed a dermal inflammatory infiltrate composed primarily of neutrophils and eosinophils with rare flame figures in the dermis. There was minimal fat seen in this biopsy. A differential diagnosis of Wells or Sweet's syndrome was entertained, and he was placed on 60 mg/day prednisone with no resolution of his symptoms. The patient's past medical history included hypertension, hyperlipidemia, peripheral neuropathy, and hiatal hernia. His family history was significant for emphysema in both parents and coronary artery disease in his father. Both of his parents smoked cigarettes. His grandfather, who was a coal miner, also had emphysema. Whilst on antibiotics and prednisone, the plaques on the patient's right thigh, right abdomen, and left chest expanded and ulcerated, draining an oily liquid (Figs 1 and 2). An incisional biopsy was obtained from his thigh. Histopathology showed a septal and lobular panniculitis with fat necrosis, neutrophils, and histiocytes (Fig. 3). Special stains for organisms were negative. Tissue sent for bacterial and fungal culture had no growth. Amylase and lipase levels were normal. Rheumatoid factor, antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), cryoglobulins, and antiphospholipid antibodies were all normal. The alpha1-antitrypsin level was low at 25 mg/dL (ref. 75-135). The alpha1-antitrypsin phenotype was PiZZ. The patient had a normal glucose-6-phosphate dehydrogenase level and was placed on dapsone 200 mg/day. The inflammation resolved and, over the course of several months, the involved areas healed with scarring. The patient denied any pulmonary complaints but, during his hospitalization, was found incidentally to have an oxygen saturation of 88% on room air. He was sent for evaluation by a pulmonologist, and pulmonary function tests revealed a mixed restrictive and obstructive pattern with a forced expiratory volume in 1 to forced vital capacity (FEV(1)/FVC) ratio of 63% of predicted. He had never smoked. He was placed on supplemental oxygen but, as his pulmonary disease has been stable, he has not been treated with intravenous antitrypsin inhibitor.
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PMID:alpha1-Antitrypsin deficiency presenting with panniculitis and incidental discovery of chronic obstructive pulmonary disease. 1791 Jul 20

Diabetes mellitus is one of the most common chronic diseases in the United States and peripheral neuropathy (PN) affects at least 50% of diabetic patients. Medications available for patients ameliorate symptoms (pain), but do not protect against cellular damage and come with severe side effects, leading to discontinued use. Our research group uses differentiated SH-SY5Y cells treated with advanced glycation end products (AGE) as a model to mimic diabetic conditions and to study the mechanisms of oxidative stress mediated cell damage and antioxidant protection. N-acetylcysteine (NAC), a common antioxidant supplement, was previously shown by our group to fully protect against AGE-induced damage. We have also shown that 3H-1,2-dithiole-3-thione (D3T), a cruciferous vegetable constituent and potent inducer of nuclear factor (erythroid-derived 2)- like 2 (Nrf2), can significantly increase cellular GSH concentrations and protect against oxidant species-induced cell death. Paradoxically, D3T conferred no protection against AGE-induced cell death or neurite degeneration. In the present study we establish a mechanism for this paradox by showing that D3T in combination with AGE increased oxidant species generation and depleted GSH via inhibition of glutathione reductase (GR) activity and increased expression of the NADPH generating enzyme glucose-6-phosphate dehydrogenase (G6PD). Blocking NADPH generation with the G6PD inhibitor dehydroepiandrosterone was found to protect against AGE-induced oxidant species generation, loss of viability, and neurite degeneration. It further reversed the D3T potentiation effect under AGE-treated conditions. Collectively, these results suggest that strategies aimed at combating oxidative stress that rely on upregulation of the endogenous antioxidant defense system via Nrf2 may backfire and promote further damage in diabetic PN.
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PMID:D3T acts as a pro-oxidant in a cell culture model of diabetes-induced peripheral neuropathy. 3059 78