Positive impact of dietary water on in vivo epidermal water physiology.

BACKGROUND/PURPOSE: The importance of water in human physiology is well known, also for skin functionality. This study was conducted to assess the effects of dietary water on epidermal skin hydration in healthy females. METHODS: Thirty-four healthy females (mean 24.5 ± 6.34 years old) were selected and characterized according to their dietary daily habits, by a previously validated Food Frequency Questionnaire. For 1 month, these subjects were asked to add 2 L/day of water to their regular dietary habits. Measurements took place at day D0, D15, and D30, and involved general variables (body weight, blood pressure, Body Mass Index) and specific skin physiological variables in five anatomical sites (ventral forearm, anterior leg, dorsal hand, zygomatic area, and forehead) involving epidermal superficial and deep hydration, by capacitance and transepidermal water loss (TEWL). RESULTS: This water overload (2 L/day/30 days) did not change the blood volume or weight of the individuals. However, both superficial and deep skin hydration were clearly in those individuals that regularly consumed lees water per day. No significant effect was observed in the TEWL. CONCLUSIONS: This study clearly suggests that dietary water intake seems to influence skin water content. Nevertheless further in vivo investigations involving other variables, such as biomechanical descriptors, should follow to look deeper into this aspect of skin physiology.

Atherogenic effects of cyclosporine in an experimental model of arterial autograft.

One of the effects attributed to CsA is a possible acceleration of atherogenic processes, which contributes to the failure of transplanted organs. This study was undertaken to evaluate the effect of CsA and two vehicles, cremophor and ethanol, in an experimental model of arterial autograft in the rat. Female Sprague-Dawley rats were distributed into 3 study groups: Group 1 (control) had an arterial autograft in the common iliac artery without pretreatment; group 2 (CsA-cremophor) animals were pretreated with a daily dose of CsA (5 mg/kg, Sandimmun) for 4 days before the autograft was made; and group 3 (CsA-ethanol + Tween) animals were pretreated for 4 days before implantation of the autograft with CsA in a vehicle of ethanol + Tween at the same dose as used in group 2 (5 mg/kg). The study periods were 7, 14, 21, 30, and 50 postoperative days. Studies were made by optical microscopy, transmission electron microscopy, scanning electron microscopy, and autoradiography. Evaluation of the results showed that in the control group the postoperative repair process lead to formation of an intimal neolayer throughout the entire surgical zone, with scant participation of white cells. Group 2 (CsA-cremophor) had a marked increase in luminal thrombogenicity, important adhesion and infiltration of white cells, loss of smooth muscle cells in the medial layer, and atherogenic degeneration of the medial layer. The generation of the neointimal layer is delayed by 2 weeks with respect to the control group. However, once the neointimal begins to form, its thickness increases rapidly, reaching values similar to those seen in the control group at 50 days. The myointima also shows atherogenic characteristics, such as monocyte-macrophage infiltration and dystrophic calcification. In group 3 (CsA-ethanol+Tween, that is, CsA in a nonoleaginous vehicle), the effects were similar to those seen in group 2 (CsA-cremophor), with a reduction in the presence of lipid-laden cells in the medial layer. Based on these observations, we conclude that CsA per se induced atherogenic changes in the repair process of the arterial lesion that were independent of the vehicle of administration. CsA delayed, but did not inhibit, formation of a myointima and the myointima formed exhibited atherogenic characteristics. The most important effects were noted in the medial layer, which experienced intense degeneration.

Non-immunological release of histamine from rat mast cells elicited by antineoplastic agents.

We studied the histamine-releasing activity of several antineoplastic drugs on rat pleural and peritoneal mast cells. The drugs tested included the nitrogen mustards cyclophosphamide and ifosfamide, the nitrosourea carmustine, the triazene dacarbazine, the folic acid analogue methotrexate, the pyrimidine analogue cytarabine and fluorouracil, the vinca alkaloids vinblastine, vincristine and Vinorelbine, the epipodophyllotoxins etoposide and teniposide, and the enzyme L-asparaginase. Methotrexate, carmustine, fluorouracil, vinblastine and vincristine failed to elicit histamine release on rat mast cells. All of the other drugs evoked histamine release in both the presence and the absence of extracellular calcium, but ifosfamide, cytarabine and asparaginase induced a much lower release in the absence of this cation. The response elicited by cytarabine and etoposide was much higher in pleural than in peritoneal mast cells. These results indicate that some antineoplastic drugs may directly activate the release of histamine, which could contribute to some of their secondary effects.

Lack of specific saxitoxin binding to rat mast cells.

We studied whether or not mast cells are endowed with specific sodium channels, by using tritiated saxitoxin which binds to site 1 of sodium channels on excitable tissues. Our results suggest that rat pleural and peritoneal mast cells lack specific sodium channels.

Changes in rat mast cell responses in sodium-free media. Lack of demonstrable sodium channel activity.

Exposure of rat mast cells to isotonic sucrose (employed as a sodium free medium) increased several-fold the sensitivity to calcium, which itself became a stimulus for exocytosis. Concentrations of the cation as low as 25 microM permitted maximal histamine release. Preincubation of cells in sucrose to allow sodium efflux before adding the ionophore A23187 led to a slower release of histamine. We postulate that sodium efflux can generate a membrane potential that causes the increased sensitivity to calcium and the delay in response after preincubation. The response to A23187 is somewhat unspecific since the ionophore can release histamine from internal calcium reservoirs. Saxitoxin or veratridine did not affect cell responses, so that sodium activity is not mediated through defined sodium channels.