Carbohydrate hastens hypervolemia achieved through ingestion of aqueous sodium solution in resting euhydrated humans.

PURPOSE: Ingesting beverages containing a high concentration of sodium under euhydrated conditions induces hypervolemia. Because carbohydrate can enhance interstitial fluid absorption via the sodium-glucose cotransporter and insulin-dependent renal sodium reabsorption, adding carbohydrate to high-sodium beverages may augment the hypervolemic response. METHODS: To test this hypothesis, we had nine healthy young males ingest 1087 ± 82 mL (16-17 mL per kg body weight) of water or aqueous solution containing 0.7% NaCl, 0.7% NaCl + 6% dextrin, 0.9% NaCl, or 0.9% NaCl + 6% dextrin under euhydrated conditions. Each drink was divided into six equal volumes and ingested at 10-min intervals. During each trial, participants remained resting for 150 min. Measurements were made at baseline and every 30 min thereafter. RESULTS: Plasma osmolality decreased with water ingestion (P ≤ 0.023), which increased urine volume such that there was no elevation in plasma volume from baseline (P ≥ 0.059). The reduction in plasma osmolality did not occur with ingestion of solution containing 0.7% or 0.9% NaCl (P ≥ 0.051). Consequently, urine volume was 176-288 mL smaller than after water ingestion and resulted in plasma volume expansion at 60 min and later times (P ≤ 0.042). In addition, net fluid balance was 211-329 mL greater than after water ingestion (P ≤ 0.028). Adding 6% dextrin to 0.7% or 0.9% NaCl solution resulted in plasma volume expansion within as little as 30 min (P ≤ 0.026), though the magnitudes of the increases in plasma volume were unaffected (P ≥ 0.148). CONCLUSION: Dextrin mediates an earlier hypervolemic response associated with ingestion of high-sodium solution in resting euhydrated young men. (247/250 words).

Effect of voluntary hypocapnic hyperventilation on the relationship between core temperature and heat loss responses in exercising humans.

Two thermolytic thermoregulatory responses, cutaneous vasodilation and sweating, begin when core temperature reaches a critical threshold, after which response magnitudes increase linearly with increasing core temperature; thus the slope indicates response sensitivity. We evaluated the influence of hypocapnia induced by voluntary hyperventilation on the core temperature threshold and sensitivity of thermoregulatory responses. Ten healthy males performed 15 min of cycling at 117 W (29.5°C, 50% RH) under three breathing conditions: 1) spontaneous ventilation, 2) voluntary normocapnic hyperventilation, and 3) voluntary hypocapnic hyperventilation. In the hypocapnic hyperventilation trial, end-tidal CO2 pressure was reduced throughout the exercise, whereas it was maintained around the normocapnic level in the other two trials. Cutaneous vascular conductances at the forearm and forehead were evaluated as laser-Doppler signal/mean arterial blood pressure, and the forearm sweat rate was measured using the ventilated capsule method. Esophageal temperature threshold was higher for the increase in cutaneous vascular conductance in the hypocapnic than normocapnic hyperventilation trial at the forearm (36.88 ± 0.36 vs. 36.68 ± 0.34°C, P < 0.05) and forehead (36.89 ± 0.31 vs. 36.75 ± 0.31°C, P < 0.05). The slope relating esophageal temperature to cutaneous vascular conductance was decreased in the hypocapnic than normocapnic hyperventilation trial at the forearm (302 ± 177 vs. 420 ± 178% baseline/°C, P < 0.05) and forehead (236 ± 164 vs. 358 ± 221% baseline/°C, P < 0.05). Neither the threshold nor the slope for the forearm sweat rate differed significantly between the hypocapnic or normocapnic hyperventilation trials. These findings indicate that in exercising humans, hypocapnia induced by voluntary hyperventilation does not influence sweating, but it attenuates the cutaneous vasodilatory response by increasing its threshold and reducing its sensitivity.

Hypervolemia induced by fluid ingestion at rest: effect of sodium concentration.

PURPOSE: Sodium drink is used as a countermeasure against body fluid loss. However, high concentrations of sodium may cause gastrointestinal upset (e.g., diarrhea). We sought to determine the sodium concentration that induces hypervolemia with a minimal risk of gastrointestinal disturbance. METHODS: Eight healthy active males rested in a chair and ingested a given amount (16-17 ml kg body mass(-1)) of water (W) or solution containing 60, 120 or 180 mmol l(-1) Na(+) (60, 120 and 180Na trials) in 6 equal portions at 10 min intervals. To standardize their hydration status, subjects consumed the same meal and water 2 h before each trial. Drink trials were performed on separate days, and the order was randomized. The change in plasma volume (PV) from pre-drink status was estimated from the hemoglobin concentration and hematocrit every 30 min for 150 min after initiation of drinking. RESULTS: Subjects began trials in a euhydrated state, as reflected by their plasma osmolality (in mmol l(-1): W, 289.4 ± 1.4; 60Na, 287.0 ± 3.5; 120Na, 287.6 ± 2.3; 180Na, 288.9 ± 3.3). At 120 min, PV had not increased from the pre-drink value in the W (-0.8 ± 4.5 %) or 60Na (2.4 ± 4.9 %) trials, but it increased to similar degrees in the 120Na (7.2 ± 4.6 %) and 180Na (9.4 ± 6.6 %) trials. No diarrhea was reported in the W or 60Na trials, but it was reported in the 120Na (n = 1) and 180Na (n = 6) trials. CONCLUSIONS: Beverages containing 120 mmol l(-1) Na(+) induce hypervolemia with a minimum incidence of gastrointestinal problems.

Effect of voluntary hypocapnic hyperventilation on cutaneous circulation in resting heated humans.

Hypocapnia attenuates the sweat response normally seen in hyperthermic resting subjects, but its effect on the blood flow response in their nonglabrous skin under the same hyperthermic conditions remains unclear. In the present study, we investigated whether hypocapnia induced by voluntary hyperventilation affects the blood flow response to heat stress in the nonglabrous skin of resting humans. Nine healthy male subjects were passively heated using legs-only hot water immersion and a water-perfused suit, which caused esophageal temperature (T(es)) to increase by as much as 1.0°C. During normothermia and at +0.6°C T(es) and +1.0°C T(es), the subjects performed two voluntary 7-min hyperventilation (minute ventilation = 40 l/min) trials (hypocapnic and eucapnic) in random order. End-tidal CO(2) pressure was reduced by 23-25 torr during hypocapnic hyperventilation, but it was maintained at the spontaneous breathing level during eucapnic hyperventilation. Cutaneous blood flow was evaluated as the cutaneous red blood cell flux in the forearm (CBF(forearm)) or forehead (CBF(forehead)) and was normalized to the normothermic spontaneous breathing value. Hypocapnic hyperventilation at +0.6°C T(es) was associated with significantly reduced CBF(forearm), compared with eucapnic hyperventilation, after 5-7 min of hyperventilation (395 to 429 vs. 487 to 525% baseline, P < 0.05). No significant difference in CBF(forehead) was seen during hypocapnic hyperventilation compared with eucapnic hyperventilation at +0.6°C T(es) or +1.0°C T(es). These results suggest that in resting humans, hypocapnia achieved through voluntary hyperventilation attenuates the increase in cutaneous blood flow elicited by moderate heat stress in the nonglabrous skin of the forearm, but not the forehead.

Immunosuppressive effects of photodynamic therapy by topical aminolevulinic acid.

Photodynamic therapy (PDT) has been used for inflammatory skin disorders as well as superficial skin cancers such as solar keratosis and Bowen's disease. Whether PDT with topical application of aminolevulinic acid (ALA) and exposure to visible light has a similar immunosuppressive action to ultraviolet phototherapy was investigated using a murine contact hypersensitivity (CHS) model. The number of epidermal Langerhans cells (LC) was decreased with their morphological changes 1 day after PDT with the minimal level at 5 days and gradual recovery thereafter. Conversely, the number of CD11c(+) I-A(+) cells was significantly increased in the draining lymph nodes after PDT. This suggests that LC moved from PDT-treated skin, resulting in the decrement of epidermal LC and migration to lymph nodes. CHS response to DNFB applied on the PDT-treated skin with 20% ALA and 40 J/cm(2) visible light was significantly suppressed (local immunosuppression). When mice were treated with 80 J/cm(2) of PDT, CHS response to the antigen applied on untreated distant skin was also significantly suppressed (systemic immunosuppression). The locally or systemically immunosuppressed mice by PDT were attempted to sensitize again with DNFB on non-treated skin, but elicitation responses were significantly suppressed. However, these mice were able to be sensitized with another hapten, oxasolone. Thus, a hapten-specific immunological unresponsiveness (tolerance) was induced in mice by topical ALA-PDT. These findings suggest that PDT has a potential immunological contribution to clinical efficacy for inflammatory diseases identical to ultraviolet phototherapies.

Ultraviolet B radiation suppresses Langerhans cell migration in the dermis by down-regulation of alpha4 integrin.

BACKGROUND/PURPOSE: Ultraviolet B (UVB) radiation affects the migration and function of epidermal Langerhans cells (LC) and causes immunosuppression of contact hypersensitivity. It is known that LC leaves the epidermis after exposure to UVB. To know the behavior of LC in the dermis after UVB radiation, we studied the effect of UVB radiation on the expression of integrin families on freshly isolated or cultured murine LC. We also examined whether UVB radiation affects the migration of LC to secondary lymphoid tissue chemokine (SLC/6Ckine). METHODS: Integrin expressions of murine LC cultured in epidermal cell suspension were analyzed using flowcytometry. We used murine LC sorted flowcytometrically for binding assay to extracellular matrix and for migration assay to chemokine. Skin explant assay and immnohistochemical staining for 'cords formation' were performed as previously described. RESULTS: Twenty and 40 mJ/cm2 of UVB radiation down-regulated the expression of alpha4 integrin on 24 h-cultured LC, but not that of alpha6, beta1, or beta4 integrin. The number of cultured LC adhered to fibronectin, a ligand for alpha4 integrin, was decreased after UVB irradiation, while that to laminin, a ligand for alpha6 integrin, was not influenced. UVB radiation reduced the number of migrating LC to SLC. Furthermore, skin sheet explant experiments showed that UVB radiation inhibited the 'cords' formation in dermal vessels of the 48 h-cultured skin. CONCLUSIONS: These data suggest that UVB radiation may suppress the migration of LC from the dermis to lymphatic vessels. UVB radiation may downregulate the adherence of LC to dermal fibronectin and migration to SLC, and consequently suppress the migration of LC from the UVB-irradiated dermis to lymphatics.

The photocarcinogenesis of antibiotic lomefloxacin and UVA radiation is enhanced in xeroderma pigmentosum group A gene-deficient mice.

Lomefloxacin (LFLX) is phototoxic and phototumorigenic, but the mechanisms of phototumorigenesis of quinolone drugs have not been fully elucidated. Formation of cyclobutane pyrimidine dimers (CPD) by UVB radiation is primarily involved in the carcinogenesis of ultraviolet (UV) radiation. On the other hand, UVA region is responsible to photobiologic reactions of quinolone drugs. To know if CPD can be formed by UVA radiation in the presence of LFLX and is involved in the phototumorigenesis, we used xeroderma pigmentosum (XP) group A gene-deficient (XPA-/-) mouse, which is defective in nucleotide excision repair. XPA-/- and XPA+/+ mice were irradiated to 5 J per cm2-UVA with or without the administration of LFLX. In XPA-/- mice treated with LFLX, the first skin tumor appeared after exposures to 75 J per cm2 in 5 wk. In XPA+/+ mice treated with LFLX, the first tumor appeared after exposures to 345 J per cm2 in 23 wk. Immunohistochemically, CPD formation was observed after UVA-exposure in the skin of XPA+/+ as well as XPA-/- mice which had been given LFLX. The CPD disappeared, however, earlier from XPA+/+ mice than from XPA-/- mice. The acute inflammatory reaction after LFLX administration and exposure to UVA were greatly enhanced in XPA-/- mice. These results indicate that UVA exposure induces DNA damage in the form of CPD in the presence of LFLX, which exerts phototoxicity and phototumorigenesis.

Effects of UVB on fascin expression in dendritic cells and Langerhans cells.

BACKGROUND: Fascin is an actin-binding protein that regulates the rearrangement of cytoskeletal elements and their interactions with the cell membrane. Previous studies have indicated that fascin expression is enhanced in DC upon maturation and plays a critical role in T cell activation. Ultraviolet irradiation exerts immunosuppressive effects. OBJECTIVE: We examined the effects of UVB irradiation on the interaction of DC/LC with T cells through fascin. METHOD: Murine bone marrow-derived DC (BM-DC) were induced by recombinant murine GM-CSF and LPS, and UVB irradiation was applied prior to supplementation with LPS. I-A(+) cells (Langerhans cells (LC)) in the epidermal cell suspensions were exposed to UVB irradiation at the beginning of the 24-h culture. BM-DC and LC were analysed by immunohistochemical staining and flow cytometric analyses. To evaluate the effects of UVB irradiation on DC-T cell binding, we examined the clustering of BM-DC with allogeneic CD4(+) T cells under a confocal microscope. RESULTS: Fascin expression in BM-DC and LC was decreased by UVB irradiation. Furthermore, UVB irradiation reduced the ability of BM-DC to cluster with allogeneic CD4(+) T cells. Polarization of fascin and filamentous actin (F-actin) at the point of contact of BM-DC with T cells was also disturbed by UVB irradiation. CONCLUSION: These results suggest that the suppression of fascin expression by UVB irradiation down-regulates the rearrangement of the cytoskeleton and, thereby, antigen presentation in DC/LC.

Ultraviolet radiation-induced impairment of tumor rejection is enhanced in xeroderma pigmentosum a gene-deficient mice.

Xeroderma pigmentosum (XP)A gene-deficient mice display dermatologic abnormalities similar to human XP, such as enhanced ultraviolet (UV)-induced acute inflammation and high incidence of UVB-induced skin cancer. We have previously reported that UVB-induced immunosuppression of contact hypersensitivity was greatly enhanced in XPA mice. In the present study, we examined the effects of UVB radiation on tumor rejection in XPA mice. Tumor cells established from UVB-induced squamous cell carcinoma in XPA mice were injected subcutaneously. No difference in the development of tumors was observed between the non-irradiated XPA and wild-type mice. Tumors developed, grew in size, and reached the maximum at 7-10 d after the inoculation. Thereafter, all tumors decreased in size and were completely rejected by 4 wk in both strains of mice. When tumor cells were inoculated into the skin that had been irradiated with 50-150 mJ per cm2 of UVB, tumor grew in 60% (12 of 20) of the XPA mice, but only in 4% (one of 23) of wild-type mice. Phenotyping of tumor-infiltrating cells revealed that the migration of natural killer cells and CD8+ T cells was inhibited in UVB-irradiated XPA mice. These data suggest that enhanced UVB-induced impairment of tumor rejection could be partially involved in the cancer development of XP patients.

Therapeutic and prophylactic effects of PUVA photochemotherapy on atopic dermatitis-like lesions in NC/Nga mice.

BACKGROUND: Psoralens and ultraviolet A radiation (PUVA) photochemotherapy has been used for severe cases of atopic dermatitis (AD). To understand the mechanisms of action is important for the choice of treatments. AD-like lesions can be induced experimentally in NC/Nga mice. OBJECTIVES: To evaluate clinically and histologically the therapeutic and prophylactic effects of PUVA on AD-like dermatitis using NC/Nga mice. METHODS: PUVA therapy was performed with intraperitoneal injection of 4 mg/kg of 8-methoxypsoralen (8-MOP) and 4 J/cm(2)-UVA irradiation before and after development of AD-like lesions in NC/Nga mice which had been maintained in a conventional room (Conv-NC/Nga mice). Clinical skin conditions were evaluated periodically by a clinical severity score defined. Lesions were histologically examined in haematoxylin-eosin or toluidine blue-stained sections. Plasma levels of total IgE were measured at various time points. RESULTS: In Conv-NC/Nga mice infested with mite, AD-like lesions started to develop at 8 week of age and thereafter increased in severity score. PUVA therapy at lower does than minimal phototoxic dose suppressed the development of dermatitis and was also therapeutically effective against established lesions. Proliferation of dermal mast cells in AD-like lesions was suppressed, but IgE hyperproduction was not changed after PUVA. CONCLUSIONS: These observations suggest that PUVA photochemotherapy reveals not only therapeutic but also prophylactic effects on human AD.