Effects of acute dietary nitrate supplementation on cold-induced vasodilation in healthy males.

PURPOSE: Cold-induced vasodilation (CIVD) is a paradoxical rise in blood flow to the digits that occur during prolonged cold exposure. CIVD is thought to occur through active vasodilation and/or sympathetic withdrawal, where nitric oxide (NO) may play a key role in mediating these mechanisms. Beetroot juice (BRJ) is high in dietary nitrate (NO3-) which undergoes sequential reduction to nitrite (NO2-) and subsequently NO. Using a double-blind, randomized, crossover design, we examined the effect of acute BRJ supplementation on the CIVD response in 10 healthy males. METHODS: Participants had a resting blood pressure measurement taken prior to ingesting 140 mL of nitrate-rich BRJ (13 mmol NO3-) or a NO3--free placebo (PLA). After 2 h, participants immersed their hand in neutral water (~ 35 °C) for 10 min of baseline before cold water immersion (~ 8 °C) for 30 min. Laser-Doppler fluxmetry and skin temperature were measured continuously on the digits. RESULTS: Compared to PLA (100 ± 3 mmHg), acute BRJ supplementation significantly reduced mean arterial pressure at -30 min (96 ± 2 mmHg; p = 0.007) and 0 min (94 ± 2 mmHg; p = 0.008). Acute BRJ supplementation had no effect on Laser-Doppler fluxmetry during CIVD (expressed as cutaneous vascular conductance) measured as area under the curve (BRJ: 843 ± 148 PU mmHg-1 s; PLA: 1086 ± 333 PU mmHg-1 s), amplitude (BRJ: 0.60 ± 0.12 PU mmHg-1; PLA: 0.69 ± 0.14 PU mmHg-1), and duration (BRJ: 895 ± 60 s; PLA: 894 ± 46 s). CONCLUSION: Acute BRJ supplementation does not augment the CIVD response in healthy males.

Separate and combined effects of dehydration and thirst sensation on exercise performance in the heat.

Using intravenous infusion, we separated the physiologic consequences of 3% body mass dehydration from the conscious awareness of fluid replacement on time trial (TT) performance in the heat. Eleven trained cyclists performed 90 min of steady-state (50% V ˙ O 2 peak ) cycling followed by a self-paced 20-km TT in a hot-dry (35 °C, 10% relative humidity, wind speed 3.0 m/s) environment while euhydrated-not thirsty (EU-NT), euhydrated-thirsty (EU-T), dehydrated-not thirsty (DH-NT), or dehydrated-thirsty (DH-T). Thirst was manipulated by providing (NT) or withholding (T) ad libitum 35 °C water oral rinse. Distinct hydration states existed, with 0.4 ± 0.5% dehydration following the 20-km TT (EU) compared with 3.2 ± 0.6% in DH (P < 0.001). Greater perceived thirst existed in T (7 ± 2 on a 1-9 scale) than NT (4 ± 2, P < 0.001) after the TT. No significant differences in power output existed during the TT between hydration (EU 202.9 ± 36.5 W vs DH 207.0 ± 35.9 W, P = 0.362) and thirst conditions (NT 203.3 ± 35.6 W vs T 206.6 ± 36.8 W, P = 0.548), nor were there differences in completion time (P = 0.832) or pacing profile (P = 0.690). Within the range of up to 3% body mass loss, neither the physiologic effects from lowered hydration status nor the perception of thirst, separately or combined, affected sustained submaximal exercise performance in the heat for a healthy and fit population.

Compression garments do not alter cerebrovascular responses to orthostatic stress after mild passive heating.

Whole-body heating increases the likelihood of syncope, whereas utilizing lower-body compression garments may reduce syncope risk. We hypothesized that graded compression garments would reduce the typically observed large postural reductions in arterial blood pressure and middle cerebral artery velocity, in normothermia and especially once passively heat stressed. Fifteen men (age: 27 ± 4 years, aerobic fitness range: 30-75 mL/kg(/) min) completed a supine-to-stand orthostatic challenge for 3 min at normothermia and after passive heating (esophageal temperature, +0.5 °C from baseline) on two occasions (> 7 days): once wearing commercially available compression trousers and once wearing low-compression placebo trousers (randomized order). Blood flow velocity in the middle cerebral artery (transcranial Doppler), mean arterial blood pressure (mean BP: Finometer) and end-tidal carbon dioxide pressure were measured continuously. During normothermia, compression, garments did not alter the magnitude of the postural changes in mean BP or middle cerebral artery velocity. After passive heating, although the magnitudes of these changes were exaggerated, they were not significantly affected by compression garments. Compression garments did not attenuate the initial or sustained orthostatic hypotension associated with posture change, either during normothermia or following passive heat stress.

Sex differences in the physiological responses to exercise-induced dehydration: consequences and mechanisms.

Physiological strain during exercise is increased by mild dehydration (∼1%-3% body mass loss). This response may be sex-dependent, but there are no direct comparative data in this regard. This review aimed to develop a framework for future research by exploring the potential impact of sex on thermoregulatory and cardiac strain associated with exercise-induced dehydration. Sex-based comparisons were achieved by comparing trends from studies that implemented similar experimental protocols but recruited males and females separately. This revealed a higher core temperature (Tc) in response to exercise-induced dehydration in both sexes; however, it seemingly occurred at a lower percent body mass loss in females. Although less clear, similar trends existed for cardiac strain. The average female may have a lower body water volume per body mass compared with males, and therefore the same percent body mass loss between the sexes may represent a larger portion of total body water in females potentially posing a greater physiological strain. In addition, the rate at which Tc increases at exercise onset might be faster in females and induce a greater thermoregulatory challenge earlier into exercise. The Tc response at exercise onset is associated with lower sweating rates in females, which is commonly attributed to sex differences in metabolic heat production. However, a reduced sweat gland sensitivity to stimuli, lower fluid output per sweat gland, and sex hormones promoting fluid retention in females may also contribute. In conclusion, the limited evidence suggests that sex-based differences exist in thermoregulatory and cardiac strain associated with exercise-induced dehydration, and this warrants future investigations.

Physiological strain and countermeasures with firefighting.

Protective clothing is integral to the task of firefighting, but at the same time can increase physiological strain and impair work capacity. Encapsulation of the head and the high thermal resistance and/or low water vapor permeability of the clothing ensemble impede evaporative heat dissipation, thus elevating the rate of heat storage and creating a state of uncompensable heat stress (UHS). In addition, the additional weight from carrying a supplemental air supply and the greater respiratory work of breathing through a regulator can create a negative spiral of thermal hyperpnea from greater respiratory demands and metabolic heat production. The elevated respiratory demands also increase cardiac strain and potentially the risk for myocardial events. Tolerance time during UHS is determined by three factors: the core temperature at the beginning of the heat stress exposure, the core temperature that can be tolerated before exhaustion or collapse ensues, and the rate of increase in core temperature from the beginning to end of the heat stress exposure. Protective clothing is often employed in highly dynamic environments, making portability, longevity and integration with the task requirements and clothing critical design characteristics for countermeasures. To date, most countermeasures have been relatively indirect in nature, primarily with alterations in work scheduling along with physiological manipulations such as cooling manipulations during recovery periods. Advances are required in materials science to develop lighter and less restrictive protective equipment, concurrent with cooling strategies that target specific regions or which can be effectively implemented during exercise.

Human conscious response to thermal input is adjusted to changes in mean body temperature.

OBJECTIVE AND DESIGN: To detect the dependable criteria of behavioural thermoregulation through modelling temperature fluctuations of individuals allowed to freely manipulate inlet water temperature of a liquid conditioning garment (LCG) during 130 min of passive exposure to -20 degrees C interspersed with a 10 min period of moderate exercise at the 65th minute using a double-blind experiment. PARTICIPANTS: Eleven volunteers (5 women; 23.40 (SD 2.09) years; BMI: 23.24 (SD 2.19)) who lacked previous experience with LCG and cold exposure experiments. RESULTS: Despite variations in core and skin temperatures, thermal comfort, thermal sensation, and mean body temperature did not fluctuate significantly over time. Participants were able to find a desired level of LCG inlet temperature within 25 minutes which was maintained at similar levels until the 65th minute of the cold exposure. During exercise, LCG inlet water temperature decreased significantly. Regression models demonstrated that mean skin temperature and change in mean body temperature were significantly associated with thermal comfort and thermal sensation. Subsequent models revealed that, although all temperature variables were associated with LCG inlet water temperature, the coefficient of determination mainly depended on mean skin temperature and change in mean body temperature. The involvement of skin temperature was anticipated as the liquid conditioning garment was in contact with the skin. CONCLUSIONS: Humans generate conscious thermoregulatory responses in resting and exercise conditions during exposures to cold environments that are aimed towards maintaining a threshold mean body temperature, rather than temperature changes in individual body regions.

Influence of body heat content on hand function during prolonged cold exposures.

We examined the influence of 1) prior increase [preheating (PHT)], 2) increase throughout [heating (HT)], and 3) no increase [control (Con)] of body heat content (H(b)) on neuromuscular function and manual dexterity of the hands during a 130-min exposure to -20 degrees C (coldEx). Ten volunteers randomly underwent three passive coldEx, incorporating a 10-min moderate-exercise period at the 65th min while wearing a liquid conditioning garment (LCG) and military arctic clothing. In PHT, 50 degrees C water was circulated in the LCG before coldEx until core temperature was increased by 0.5 degrees C. In HT, participants regulated the inlet LCG water temperature throughout coldEx to subjective comfort, while the LCG was not operating in Con. Thermal comfort, rectal temperature, mean skin temperature, mean finger temperature (T(fing)), change in H(b) (DeltaH(b)), rate of body heat storage, Purdue pegboard test, finger tapping, handgrip, maximum voluntary contraction, and evoked twitch force of the first dorsal interosseus muscle were recorded. Results demonstrated that, unlike in HT and PHT, thermal comfort, rectal temperature, mean skin temperature, twitch force, maximum voluntary contraction, and finger tapping declined significantly in Con. In contrast, T(fing) and Purdue pegboard test remained constant only in HT. Generalized estimating equations demonstrated that DeltaH(b) and T(fing) were associated over time with hand function, whereas no significant association was detected for rate of body heat storage. It is concluded that increasing H(b) not only throughout but also before a coldEx is effective in maintaining hand function. In addition, we found that the best indicator of hand function is DeltaH(b) followed by T(fing).

Evaluation of an oral care protocol intervention in the prevention of chemotherapy-induced oral mucositis in paediatric cancer patients.

Oral mucositis is the most frequent and severe complication of chemotherapy in children with cancer that can aggravate the child's clinical condition and increase the risk of infection. This prospective comparative study was designed to determine the effectiveness of a preventive oral care protocol in reducing chemotherapy-induced oral mucositis in children with cancer. During an 8-month period, 42 children aged 6 to 17 years with haematological malignancies or solid tumours were evaluated. The 21 children who were included in the first 4-month period of the study constituted the control group. Another 21 children were enrolled in the subsequent 4 months and were assigned to the experimental group, in which they were given an oral care protocol intervention. The oral care protocol consisted of tooth brushing, 0.2% chlorhexidine mouth rinse and 0.9% saline rinse. Children in both groups were evaluated twice a week for 3 weeks. The incidence of ulcerative lesions, severity of oral mucositis and the related pain intensity were used as the main outcome variables. A 38% reduction in the incidence of ulcerative mucositis was found in children using the oral care protocol compared with children in the control group. The severity of oral mucositis (P=0.000002) and the related pain (P=0.0001) were significantly reduced with the intervention. These results support the preventive use of the oral care protocol in paediatric cancer patients who undergo chemotherapy for cancer treatment.

A diabetic rabbit model for pig islet xenotransplantation.

An alloxan-diabetic rabbit model was established for the testing of the function of discordant xenogeneic pig islets isolated and purified from adult pig pancreata. The functional state of the pig islet transplants and immunological state of the rabbit recipients were assessed. Intraportal transplantation of 0.47 +/- 0.01 ml of pig islets with estimated 57418 +/- 5020 in number containing an estimated insulin content of 33.93 +/- 2.97 units (n = 7; mean +/- SEM) resulted in the normalization of blood glucose with a corresponding rise in insulin levels in the diabetic rabbit recipients for 2 days. An intravenous glucose tolerance test performed in 4 recipients during the normoglycemic period resulted in an improved K rate (2.5 +/- 0.4) over the diabetic controls, but this was significantly lower than the normal control animals (K rate = 4.5 +/- 0.4; n = 8). In vitro studies demonstrated that the preformed antibodies detected in the rabbit recipients were cytotoxic to the pig islet cells and lymphocytes. Heat treatment at 56 degrees C and mercaptoethanol treatment markedly reduced the cytotoxic activities of the sera. These findings implicated involvement of complement and IgM class antibodies in the killing of the pig islet cells. Furthermore, pig islet transplants at the kidney capsule site were coated with IgM class antibodies. This study has demonstrated that pig islets can be successfully isolated and purified in sufficient numbers for xenotransplantation studies in alloxan-diabetic rabbit. The porcine islet-to-alloxan diabetic rabbit combination can serve as a highly stringent and useful discordant model for assessing the effectiveness of various immunomodulation and immunosuppressive regimens. The finding of an optimal approach to immunorejection would potentially be applicable to actual clinical islet xenotransplantation in diabetic patients.

Successful islet allotransplantation in diabetic rats immunosuppressed with FK506: a functional and immunological study.

The effect of a novel immunosuppressive agent, FK506, on fresh islet allografts was evaluated in diabetic rats across major histocompatibility complex (MHC) barriers with respect to the transplantation (TR) site, islet source, treatment regimen, and antidonor antibody (Ab) titers of the recipients after TR. The functional periods of Wistar (Wi) islets transplanted under kidney capsule (KC) or intraportally (IPo) and of a mixture of Wi and Lewis (Le) islets under KC or IPo in nonimmunosuppressed ACI rat recipients were 6.9 +/- 0.4 (n = 7), 6.4 +/- 0.5 (n = 7), 5.6 +/- 0.4 (n = 7), and 6.2 +/- 0.4 (n = 5) days, respectively. FK506 treatment at 1 mg/kg/d intramuscularly (IM) for 2 weeks (protocol I) following islet TR under KC and IPo significantly prolonged the allograft function to more than 71.8 +/- 11.3 (n = 10) and 161.7 +/- 18.6 (n = 11) days, respectively. Additional treatment with FK506 at 1 mg/kg/wk (protocol II) further increased the islet survival under KC to more than 212.6 +/- 22.3 (n = 8) days. With this FK506 treatment protocol, the Wi + Le mixed-islet allograft function was extended to more than 106.1 +/- 10.5 (n = 7) and 167.9 +/- 28.6 (n = 7) days under KC and IPo, respectively. Nephrectomy in 8/8 ACI rats with long-term-functioning Wi (n = 6) and Wi + Le (n = 2) islet allografts resulted in their return to hyperglycemia. Immunohistochemical staining showed abundant insulin-positive cells at the graft site, with small numbers of CD4- and CD8-positive cells present in the vicinity of the normal-appearing islets. Macrophages were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Human temperature regulation during subanesthetic levels of nitrous oxide-induced narcosis.

The present study investigated whether nitrous oxide (N2O) attenuates shivering thermogenesis during cold water immersion in a dose-dependent manner. Seven male subjects were immersed to the neck for 60 min in 20 degrees C water on five separate occasions while breathing either air (AIR) or a normoxic mixture of 10, 15, 20, or 25% N2O balanced with N2. All N2O concentrations investigated caused a significant (P < 0.02) reduction in shivering thermogenesis compared with AIR. Despite similar heat flux from the skin, the relative changes in esophageal temperature from resting preimmersion levels were significantly greater (P < 0.05) during the N2O trials compared with AIR, with no significant difference among the N2O conditions. A dose-dependent trend in the perception of thermal comfort was observed for the N2O conditions. It is concluded that shivering thermogenesis, and thus thermal balance, is affected to the same degree for the range of inspired N2O concentrations investigated, with no discernable dose-dependent effect.

Heat acclimation, aerobic fitness, and hydration effects on tolerance during uncompensable heat stress.

The purpose of the present study was to determine the separate and combined effects of aerobic fitness, short-term heat acclimation, and hypohydration on tolerance during light exercise while wearing nuclear, biological, and chemical protective clothing in the heat (40 degrees C, 30% relative humidity). Men who were moderately fit [(MF); <50 ml . kg-1 . min-1 maximal O2 consumption; n = 7] and highly fit [(HF); >55 ml . kg-1 . min-1 maximal O2 consumption; n = 8] were tested while they were euhydrated or hypohydrated by approximately 2.5% of body mass through exercise and fluid restriction the day preceding the trials. Tests were conducted before and after 2 wk of daily heat acclimation (1-h treadmill exercise at 40 degrees C, 30% relative humidity, while wearing the nuclear, biological, and chemical protective clothing). Heat acclimation increased sweat rate and decreased skin temperature and rectal temperature (Tre) in HF subjects but had no effect on tolerance time (TT). MF subjects increased sweat rate but did not alter heart rate, Tre, or TT. In both MF and HF groups, hypohydration significantly increased Tre and heart rate and decreased the respiratory exchange ratio and the TT regardless of acclimation state. Overall, the rate of rise of skin temperature was less, while DeltaTre, the rate of rise of Tre, and the TT were greater in HF than in MF subjects. It was concluded that exercise-heat tolerance in this uncompensable heat-stress environment is not influenced by short-term heat acclimation but is significantly improved by long-term aerobic fitness.

The thermophysiology of uncompensable heat stress. Physiological manipulations and individual characteristics.

In many athletic and occupational settings, the wearing of protective clothing in warm or hot environments creates conditions of uncompensable heat stress where the body is unable to maintain a thermal steady state. Therefore, special precautions must be taken to minimise the threat of thermal injury. Assuming that manipulations known to reduce thermoregulatory strain during compensable heat stress would be equally effective in an uncompensable heat stress environment is not valid. In this review, we discuss the impact of hydration status, aerobic fitness, endurance training, heat acclimation, gender, menstrual cycle, oral contraceptive use, body composition and circadian rhythm on heat tolerance while wearing protective clothing in hot environments. The most effective countermeasure is ensuring that the individual is adequately hydrated both before and throughout the exercise or work session. In contrast, neither short term aerobic training or heat acclimation significantly improve exercise-heat tolerance during uncompensable heat stress. While short term aerobic training is relatively ineffective, long term improvements in physical fitness appear to provide some degree of protection. Individuals with higher proportions of body fat have a lower heat tolerance because of a reduced capacity to store heat. Women not using oral contraceptives are at a thermoregulatory disadvantage during the luteal phase of the menstrual cycle. The use of oral contraceptives eliminates any differences in heat tolerance throughout the menstrual cycle but tolerance is reduced during the quasi-follicular phase compared with non-users. Diurnal variations in resting core temperature do not appear to influence tolerance to uncompensable heat stress.

Transplantation of discordant pig islet xenografts in diabetic rats.

Xenotransplantation of pig islets under the kidney capsule (KC) of diabetic rats was performed. Natural preformed ACI rat anti-pig leukocytotoxicity, leukoagglutination and hemagglutination antibody titers ranged from Neat-1: 16, 1:8-1:32 and 1:128-1:256, respectively (n = 14). Normal ACI sera were non-toxic to pig islets during short term incubation. Pig islet xenograft survival times in the nonimmunosuppressed ACI rats, ACI rats immunosuppressed with antithymocyte serum (ATS) or cyclosporin A were 3.8 +/- 0.4 (mean +/- SE; n = 5), 10.4 +/- 0.7 (n = 13) and 6.0 +/- 1.0 (n = 5) days, respectively. Pig islets implanted in the abdominal testis of ACI recipients immunosuppressed with 5 doses ATS survived for a mean of 6.4 +/- 1.0 days (n = 7). The mean K rate following an intravenous glucose tolerance test (IVGTT) in ACI rats 1 week after transplantation with pig islet under the KC was 2.2 +/- 0.4 (n = 10) compared to that of 2.91 +/- 0.30 found in normal control rats (n = 8). Peak insulin at 1 min was 60.1 +/- 3.9 microU/ml (n = 4). Histological and immunohistochemical examination showed that the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin- and glucagon-containing cells on the day of graft removal when blood glucose had returned to hyperglycemic level. Both CD4 and CD8 positive cells were in the vicinity of the graft tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolongation of pig islet xenograft survival in rats immunosuppressed with FK506.

FK506 a new and potent immunosuppressive agent has been shown to be effective in prolonging pancreatic islet allograft survival. The present study was to determine its efficacy in prolonging pig islet xenotransplantation in two different strains of rat recipients. A total of two dosages of FK506 at 1 or 2 mg/kg per day for 2 weeks and then at weekly intervals were tested as monotherapy for their effect on the survival of renal subcapsular xenografts of purified or impure adult pig islets in inbred ACI and outbred Wistar rats. Histological assessment indicated that FK506 at 2 mg/kg per day significantly prolonged purified pig islet xenograft survival and to 7.5 months in two of three ACI recipients. Monotherapy with a lower dosage of FK506 or transplantation with impure pig islets resulted in increased graft survival time over controls, but less than that with the 2 mg/kg per day FK506. The viable pig islet xenografts showed a normal appearance and were readily identified by immunohistochemical staining for insulin and glucagon and further confirmed by immunohistochemical staining with anti-pig islet specific monoclonal antibody clone P44, developed in our laboratory. Mononuclear cell infiltration, mainly of the CD8-positive T-cell subset, increased with the duration of the graft in the recipient. By 7.5 months the majority of the xenografted islet cells were enclosed by the cellular infiltrate. The in vitro perfusion study of pig islets that had survived for 1 or 2 months in vivo showed that they were responsive to glucose stimulation with increase in insulin secretion into the perfusate. The results demonstrated that FK506 significantly prolonged pig islet survival in two rat strains and suggested that it is an effective immunosuppressant for the xenotransplantation model.

A prenatal nutrition project using dietetic students in physicians' offices.

A prenatal nutritional counseling project utilizing senior dietetic students in private physicians' offices was developed. The objectives were to provide sound nutritional information to pregnant women and a realistic work experience for students committed to a career in nutritional counseling. The results were positive for the patients, the participating physicians, and the student nutritionists. Further research is indicated to determine the specific effect of nutritional counseling on pregnancy outcomes.

Comparison of short-term aerobic training and high aerobic power on tolerance to uncompensable heat stress.

This study investigated whether, in subjects of moderate aerobic fitness, short-term aerobic training could replicate the improved physiological responses to exercise-heat stress observed in individuals with a high level of aerobic fitness. Males of moderate (MF; <50 ml x kg(-1) min(-1) VO2peak, n = 8) and high (HF; >55 ml x kg(-1) x min(-1) VO2peak, n = 8) aerobic fitness walked at 3.5 km x h(-1) in the heat (40 degrees C, 30% relative humidity) wearing nuclear, biological, and chemical protective clothing. Tests were conducted once on HF subjects and on MF subjects before (MF-Pre) and after (MF-Post) a 2-week program 6 d x week(-1) of daily aerobic training (1 h treadmill exercise at 65% VO2peak for 12 d, 22 degrees C, 40% relative humidity). The training significantly increased VO2peak by 6.5%, while heart rate (fc) and rectal temperature (Tre) rise decreased during exercise in a thermoneutral environment. HF had lower body mass and body fat content than MF, and VO2peak remained lower in MF pre-or post-training. In the heat, MF-Post had a decreased skin temperature (Tsk) and an increased sweat rate compared with MF-Pre, but no changes were observed in fc, Tre, or tolerance time (TT). No significant differences during the first 60 min in Tre and fc were observed between the MF-Post and the HF subjects, though the HF subjects exhibited a lower Tsk. The endpoint Tre, deltaTre, and TT remained significantly higher in HF than in either the MF-Pre or MF-Post subjects. It was concluded that, in preparation for exercise in an uncompensable heat stress environment, short-term aerobic training offers little, if any, benefit and is not an adequate substitute for a high level of aerobic fitness resulting from habitual exercise and training.

Breath-holding ability of offshore workers inadequate to ensure escape from ditched helicopters.

BACKGROUND: Following a helicopter ditching in water, the survival rate of individuals not mortally injured by the impact ranges from 50-85%. One possible cause for this low survival rate is that the crew and passengers cannot hold their breath underwater long enough to make the often difficult escape from an inverted and submerged helicopter. METHODS: We investigated pulmonary function, breath-holding times in air (BHTa) and water (BHTw) of 228 students enrolled in offshore survival courses required to work in either the offshore petroleum industry or in military marine aviation. Comparisons were performed based on occupation, SCUBA experience, and smoking. RESULTS: In 25 degrees C pool water, the overall BHTw ranged from 5.4 to 120 s with a median of 37 s. Of the 228 subjects, 34% had a BHTw less than the 28 s required for the complete evacuation of a Super Puma helicopter under ideal conditions. No significant differences in BHTw were observed based on either smoking history (Non-Smoker, 41.5 +/- 21.6 s; Smoker, 37.2 +/- 20.2 s) or occupation (Novice, 37.5 +/- 21.1 s; Offshore, 40.5 +/- 21.1 s; Military, 45.2 +/- 20.9 s). However, SCUBA-trained individuals had a significantly longer BHT, (47.4 +/- 21.6 s) than non-SCUBA (37.6 +/- 20.6 s), as well as a greater force vital capacity (FVC), BHTa, and subjective comfort in water. CONCLUSIONS: It is concluded that the inability to breath-hold in emergency situations is a major contributor to the low survival rates of marine helicopter ditchings. Therefore, efforts must be made to both decrease escape times and to increase survival time underwater.

Antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents on human pancreatic cancer multicellular spheroids.

Devil's club (DC, Oplopanax horridus) is an important medicinal herb of the Pacific Northwest which has significant antiproliferation activity against a variety of human tumor cell lines in vitro. This study compared the antiproliferation activity of DC extract alone, and in combination with chemotherapeutic agents gemcitabine (GEM), cisplatin (CDDP), and paclitaxel (PTX) on human pancreatic cancer PANC-1 3D spheroids and 2D monolayer cells. 3D tumor spheroids were prepared with a rotary cell culture system. PANC-1 3D spheroids were significantly more resistant to killing by DC extract, GEM and PTX compared to 2D cells, with IC50 levels closer to that observed in vivo. DC extract significantly enhanced the antiproliferation activity of CDDP and GEM at some concentrations. The bioactive compound identified as a polyacetylene showed strong antiproliferation activity against PANC-1 2D cells and 3D spheroids with IC50 at 0.73±0.04 and 3.15±0.16µM, respectively. 3D spheroids and 2D cells differentially expressed a number of apoptosis related genes. Cell cycle analysis showed that the proportion of cells in S phase was increased and in G2/M phase reduced in 3D spheroids compared to 2D cells. DC extract can potentially be used to enhance the activity of chemotherapeutic agents against pancreatic cancer cells. Use of 3D spheroid model for screening of natural products can potentially increase the efficiency in discovering in vivo bioactive compounds.