Syndrome of Inappropriate Secretion of Antidiuretic Hormone Caused by Very Short-term Use of Proton Pump Inhibitor.

Proton pump inhibitors (PPIs) are widely used medicines worldwide. However, a rare etiology of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) related to PPI was recently reported. Therefore, the putative role of PPIs in SIADH cannot be underestimated. A 78-year-old Japanese woman was admitted to our hospital for treatment of left Bell's palsy. On admission, the patient was oriented with normal laboratory data, including a serum Na level of 135 mEq/L. Oral glucocorticoids and a proton pump inhibitor were initiated in combination with oral valaciclovir. Six days later, the patient's consciousness became impaired. Laboratory data showed a serum Na level of 103 mEq/L, a urine Na level of 64.8 mEq/L, a urine K level of 43.6 mEq/L, and a urine osmolality of 450 mOsm/kg H2O. The patient met the criteria for SIADH. The initial treatment included water restriction and 3% hypertonic saline administration. The cessation of PPI significantly improved the urine diluting capacity and concomitantly increased serum Na, which indicated that the use of PPI had been responsible for the etiology of SIADH. The present case illustrates that physicians need to be aware of the uncommon adverse effects of PPI, such as SIADH.

Impaired contact hypersensitivity reaction and reduced production of vascular endothelial growth factor in tumor necrosis factor-alpha gene-deficient mice.

Tumor necrosis factor (TNF)-alpha is an important proinflammatory cytokine in contact hypersensitivity (CHS) reactions. Previous efforts to assay CHS in TNF-alpha gene-deficient (-/-) mice have demonstrated a significant reduction in ear skin weight at 24 h following challenge by oxazolone, although the mechanisms of this suppression have not been examined. To further characterize the impaired CHS during evolution of the elicitation phase in TNF-alpha -/- mice and to clarify its mechanisms, focusing on the roles of TNF-alpha and vascular endothelial growth factor (VEGF), we used an established method of CHS assay-sensitization and challenge by trinitrochlorobenzene (TNCB)- in TNF-alpha -/- and wild-type mice. We compared the histopathology of the sequential evolution of CHS between the two groups of mice and assessed both the extent of inflammatory cell infiltration and the degree of dilatation in dermal vessels labeled with CD31. We quantified the production of VEGF in the epidermis at specific time points by using a murine VEGF ELISA kit. The CHS reaction was markedly suppressed in TNF-alpha -/- mice at all time points of the elicitation phase. Histologically, in TNF-alpha -/- mice we observed diminished vascular permeability, reduced numbers of infiltrating inflammatory cells, neutrophils at 12 h, mononuclear cells and eosinophils at 24 h, and a decreased area of dilatation of vessels labeled with CD31. The level of epidermal VEGF in wild type mice increased rapidly after challenge and peaked at 24 h, paralleling the peak of ear swelling. In contrast, the peak level of epidermal VEGF in TNF-alpha -/- mice was significantly reduced. These results suggest that TNF-alpha plays an enhancing role in the elicitation phase of the CHS reaction. Diminished degrees of vascular permeability, dilatation of CD31+ vessels, and inflammatory cell infiltration in TNF-alpha -/- mice are likely to be the result of a lack of TNF-alpha and reduced production of epidermal VEGF.

Low-dose ultraviolet B rays alter the mRNA expression of the circadian clock genes in cultured human keratinocytes.

Current understanding of mammalian circadian rhythms suggests that they are regulated by light targeting signaling pathways in the hypothalamic suprachiasmatic nuclei. Recently, investigators have identified the existence of extraretinal photoreceptors and a potential role for the skin in this regulatory process has been implied. We demonstrated that mRNA of the circadian clock genes Per1, Clock, and bmal1/mop3 are expressed in normal human cultured keratinocytes. Low-dose ultraviolet B rays initially downregulate all circadian clock genes and then induce altered expression of the genes in keratinocyte cell cultures. Ultraviolet light targeting superficial layers of skin (keratinocytes) may therefore contribute to circadian rhythm modulation.