Translational research : the journal of laboratory and clinical medicine
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Editorial Comment
Stretching the search for therapeutic targets in acute lung injury.
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S1P has been demonstrated to protect against the formation of lipopolysaccharide (LPS)-induced lung edema when administered concomitantly with LPS. In the current study, we sought to determine the effectiveness of S1P to attenuate lung injury in a translationally relevant canine model of ALI when administered as rescue therapy. Secondarily, we examined whether the attenuation of LPS-induced physiologic lung injury after administration of S1P was, at least in part, caused by an alteration in local and/or systemic inflammatory cytokine expression. ⋯ Interestingly, S1P potentiated the LPS-induced systemic production of 3 inflammatory cytokines, TNF-alpha (6-fold), KC (1.2-fold), and IL-6 (3-fold), without resulting in end-organ dysfunction. In conclusion, intravenous S1P reduces inflammatory lung injury when administered as rescue therapy in our canine model of LPS-induced ALI. This improvement is observed in the absence of changes in local pulmonary inflammatory cytokine production and an augmentation of systemic inflammation.
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Methanol, ethylene glycol, and diethylene glycol intoxications can produce visual disturbances, neurologic disturbances, acute renal failure, pulmonary dysfunction, cardiac dysfunction, metabolic acidosis, and death. Metabolic acidosis and an increased serum osmolality are important clues to their diagnosis. The former reflects the organic acids produced by metabolism of the parent alcohol, whereas the latter is caused by accumulation of the offending alcohol. ⋯ In this report, we describe liquid-based tests that detect methanol, ethylene glycol, diethylene glycol, and ethanol in saliva. The tests are sensitive, and they have different specificity for each of the alcohols facilitating distinction among them. The relatively high sensitivity and specificity of the tests as a whole will facilitate the rapid diagnosis of each of these alcohol intoxications.
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The apolipoprotein E (APOE) epsilon2 allele is reported to be associated with greater risk of renal impairment in type 2 diabetes. Relationships among APOE polymorphisms, renal impairment, and biochemical parameters were explored. A prospective study of 405 consenting Chinese type 2 diabetic patients [mean age +/- standard deviation (SD): 59.2 +/- 10.3 years] without advanced complications at entry was conducted. ⋯ Baseline plasma lipid-standardized alpha-tocopherol levels were least in epsilon2 subjects with persistent albuminuria (3.6 +/- 1.1 mumol/mmol of total cholesterol plus triglycerides, P = 0.008) compared with epsilon2 subjects who had no albuminuria at entry or during follow-up (4.5 +/- 0.8 mumol/mmol of total cholesterol plus triglycerides). The APOE epsilon2 allele does not seem to be associated with increased risk of renal impairment in Chinese type 2 diabetic patients. Plasma lipid-standardized alpha-tocopherol may play a role in determining risk of renal dysfunction in type 2 diabetes.
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Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), or so-called ALA-PDT, is a standard procedure in the clinical practice. For optimal treatment of nonmelanoma skin cancer, actinic keratoses and other dermatoses improvements are required because of adverse side effects, which include pruritus, erythema, edema, and pain. (R)L-sulforaphane (SF) is a compound that protects against erythema, but it can also induce DNA fragmentation that leads to cell death by apoptosis. The aim of our study was to investigate whether SF has any impact on protoporphyrin IX (PpIX) production and on PDT effectiveness. ⋯ The synthesis of PpIX was increased by SF in human skin, but not in A431 cells. The average increase in PpIX fluorescence in human skin was 18% +/- 6% and 43% +/- 10% for ALA combined with 80 nmol/L SF and 120 nmol/L SF, respectively. Pretreatment with (R)L-sulforaphane before topical ALA-PDT may improve penetration of ALA through the stratum corneum, and, subsequently, increase PpIX synthesis.