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In complicated pregnancy, fetal hypoxemia rarely occurs in isolation but is often accompanied by fetal acidemia. There is growing clinical concern about the combined effects of fetal hypoxemia and fetal acidemia on neonatal outcome. However, the effects on the fetal defense responses to acute hypoxemia during fetal acidemia are not well understood. This study tested the hypothesis that fetal acidemia affects the fetal defense responses to acute hypoxemia. The hypothesis was tested by investigating, in the late-gestation sheep fetus surgically prepared for long-term recording, the in vivo effects of acute fetal acidemia on 1) the fetal cardiovascular responses to acute hypoxemia and 2) the neural and endocrine mechanisms mediating these responses. Under general anesthesia, five sheep fetuses at 0.8 gestation were instrumented with catheters and Transonic flow probes around the femoral and umbilical arteries. After 5 days, animals were subjected to an acute hypoxemia protocol during intravenous infusion of saline or treatment with acidified saline. Treatment with acidified saline reduced fetal basal pH from 7.35 ± 0.01 to 7.29 ± 0.01 but did not alter basal cardiovascular variables, blood glucose, or plasma concentrations of catecholamines, ACTH, and cortisol. During hypoxemia, treatment with acidified saline increased the magnitude of the fetal bradycardia and femoral vasoconstriction and concomitantly increased chemoreflex function and enhanced the increments in plasma concentrations of catecholamines, ACTH, and cortisol. Acidemia also reversed the increase in umbilical vascular conductance during hypoxemia to vasoconstriction. In conclusion, the data support our hypothesis and show that acute acidemia markedly alters fetal hemodynamic, metabolic, and endocrine responses to acute hypoxemia.
- cortisol
- catecholamines
- umbilical vascular conductance
- femoral vascular resistance
one of the most common challenges to the fetus during late gestation is an episode of O2 deprivation. Acute hypoxemia, i.e., ∼50% reduction of fetal arterial Po2 (PaO2), elicits integrated cardiovascular, metabolic, and endocrine responses that facilitate fetal survival during the period of reduced O2 availability (24, 43). In late gestation, the fetal cardiovascular defense to acute hypoxemia is triggered via a carotid chemoreflex, resulting in transient bradycardia and redistribution of the cardiac output toward essential circulations, such as those perfusing the fetal brain, heart, and adrenal glands, at the expense of peripheral vascular beds. Once initiated, the peripheral vasoconstriction is maintained by the release of vasoactive agents into the fetal circulation (6, 7, 23, 24). In addition, umbilical blood flow is maintained during acute hypoxemia or elevated when the severity of the hypoxemic challenge increases as a result of the combined effects of increased perfusion pressure and activity of nitric oxide across the umbilical vascular bed (48). The metabolic response to acute hypoxemia involves increased circulating concentrations of glucose and lactate (27, 29). The hyperglycemia during acute hypoxemia arises from the combined effects of reduced glucose consumption and increased glucose production by the fetus (27, 29); lactic acidemia results from the anaerobic metabolism of glucose in fetal peripheral tissues (9). Acute hypoxemia can also activate the pituitary-adrenal and sympathoadrenomedullary axes, peripheral effector pathways of the stress system (11). If the fall in basal PaO2 in the late-gestation fetus is greater than ∼6 mmHg, activation of the pituitary-adrenal axis leads to increased release of ACTH from the anterior pituitary and glucocorticoids from the adrenal gland (2, 10). Similarly, hypoxemia leading to activation of the sympathoadrenomedullary axis promotes secretion of catecholamines in the fetal circulation (46). The increase in circulating catecholamine concentrations in the fetus contributes to the mechanisms mediating the peripheral vasoconstrictor (32) and glucogenic responses during hypoxemia (3).
Although it is accepted that the late-gestation fetus can adapt successfully to acute hypoxemia, episodes of reduced fetal oxygenation in human pregnancy rarely occur in isolation; i.e., they are often accompanied by fetal acidemia (36). Hence, there is a growing clinical concern about the effects of the combination of fetal hypoxemia and fetal acidemia compared with the effects of fetal hypoxemia alone on neonatal outcome (14, 17, 44, 47). However, the effects on the fetal defense responses to acute hypoxemia during fetal acidemia are not well understood. The present study tested the hypothesis that fetal acidemia affects the fetal defense responses to acute hypoxemia. The hypothesis was tested by investigating, in the late-gestation sheep fetus surgically prepared for long-term recording, the in vivo effects of acute fetal acidosis on 1) the fetal cardiovascular responses to acute hypoxemia and 2) the neural and endocrine mechanisms mediating these responses. The effects of fetal acidemia on the fetal hemodynamic responses to acute hypoxemia concentrated on essential and peripheral vascular beds via continuous measurement of umbilical and femoral blood flow, respectively, via perivascular Transonic flow probes.
Surgical Preparation
All procedures were performed under the United Kingdom Animals (Scientific Procedures) Act 1986 and were approved by the Ethical Review Committee of the University of Cambridge. Five Welsh Mountain sheep fetuses were surgically instrumented for long-term recording at 125 ± 1 days of gestation (full term ∼145 days) using strict aseptic conditions (22). Food, but not water, was withheld from the pregnant ewes for 24 h before surgery. After induction with thiopentone sodium (20 mg/kg iv; Intraval Sodium, Merial Animal Health, Rhone Mérieux, Dublin, Ireland), general anesthesia (1.5–2.0% halothane in 50:50 O2-N2O) was maintained using positive-pressure ventilation. Midline abdominal and uterine incisions were made, the fetal hindlimbs were exteriorized, and, on one side, femoral arterial (0.86 mm ID, 1.52 mm OD) and venous (0.56 mm ID, 0.96 mm OD) catheters (Critchly Electrical Products, NSW, Australia) were inserted. The catheter tips were advanced to the descending aorta and inferior vena cava, respectively. Another catheter was anchored onto the fetal hindlimb for recording of the reference amniotic pressure. Transonic flow transducers were also positioned around the contralateral femoral artery (2R or 3S) and around one of the umbilical arteries, inside the fetal abdomen, close to the common umbilical artery (4SB). The uterine incisions were closed in layers, the dead space of the catheters was filled with heparinized saline (80 IU heparin/ml in 0.9% NaCl), and the catheter ends were plugged with sterile brass pins. The catheters were then exteriorized via a keyhole incision in the maternal flank and kept inside a plastic pouch sewn onto the maternal skin.
Postoperative Care
During recovery, ewes were housed in individual pens in rooms with a 12:12-h light-dark cycle; they had free access to hay and water and were fed concentrates twice daily (100 g of sheep nuts no. 6, H & C Beart, Kings Lynn, UK). Antibiotics were administered daily: penicillin G procaine (0.20–0.25 mg/kg, Depocillin; Mycofarm, Cambridge, UK) intramuscularly to the ewe and ampicillin intravenously to the fetus and into the amniotic cavity (150 mg/kg, Penbritin; SmithKline Beecham Animal Health, Hertfordshire, UK). The ewes also received 2 days of postoperative analgesia with phenylbutazone (10–20 mg/kg po; Equipalazone paste, Arnolds Veterinary Products, Shropshire, UK). Generally, normal feeding patterns were restored within 48 h of recovery. After 72 h of postoperative recovery, ewes were transferred to metabolic crates, where they were housed for the remainder of the protocol. The arterial, venous, and amniotic catheters were connected to sterile pressure transducers (COBE, Argon Division, Maxim Medical, Athens, TX), and calibrated mean fetal arterial blood pressure (corrected for amniotic pressure) and fetal heart rate (triggered via a tachometer from the pulsatility in the arterial blood pressure signal) were recorded continually using a computerized data acquisition system (Department of Physiology, Cambridge University, UK). While the animals were in the metabolic crates, the patency of the fetal catheters was maintained by a slow continuous infusion of heparinized saline (80 IU heparin/ml at 0.1 ml/h in 0.9% NaCl) containing antibiotic (1 mg/ml benzylpenicillin; Crystapen, Schering-Plough, Animal Health Division, Welwyn Garden City, UK).
Experimental Protocol
After ≥5 days of postoperative recovery, all fetuses were subjected to two experimental protocols that were carried out on consecutive days in a randomized order (Fig. 1). Each protocol consisted of a 3-h period consisting of 1.5 h of normoxia, 0.5 h of hypoxemia, and 1 h of recovery, during a slow intravenous infusion of heparinized saline vehicle (80 IU heparin/ml in 0.9% NaCl) or treatment with heparinized saline acidified with HCl (pH 0.9, 0.3 ± 0.1 ml·kg−1·min−1 iv) with infusion rates titrated to achieve a reduction in fetal arterial pH (pHa) to ∼7.29. The doses of HCl were calculated retrospectively from the fetal weights (2.9 ± 0.2 kg) obtained postmortem. All treatments started 1 h before the onset of hypoxemia and ran continuously through the hypoxemic challenge and 15 min into recovery (Fig. 1). Acute hypoxemia in the fetus was induced by maternal inhalational hypoxia. Briefly, a large transparent respiratory hood was placed over the ewe's head, and air was passed into the hood at a rate of ∼50 l/min for the 1.5-h period of normoxia. After this control period, acute fetal hypoxemia was induced for 30 min by changing the concentrations of gases breathed by the ewe to 6% O2 in N2 with small amounts of CO2 (15 l/min air, 35 l/min N2, and 1.5–2.5 l/min CO2). This mixture was designed to reduce fetal PaO2 to ∼10 mmHg and maintain arterial Pco2 (PaCO2). After 0.5 h of hypoxemia, the ewe was returned to breathing air for the 1-h recovery period. At the end of the experimental protocol, the ewes and fetuses were euthanized with a lethal dose of pentobarbitone sodium (200 mg/kg iv; Pentoject, Animal Ltd, York, UK). Autopsy was carried out at 128 ± 1 days of gestation. Each fetus was weighed, and the positions of the implanted catheters and the flow probes were confirmed.
In pilot experiments, acidified saline was infused at different concentrations, infusion rates, and durations to obtain the most suitable infusion regimen to achieve a reduction in basal fetal pHa to the required mean value. An infusion of acidified (pH 0.9) saline at a rate of 0.3 ± 0.1 ml·kg−1·min−1 led to a decrement from baseline in fetal pHa of ∼0.07 and persistently maintained the pH at this level for up to 3 h. During these pilot experiments, there was no change in any of the hemodynamic variables measured in the fetus or in fetal blood gases during 3 h of acid infusion under baseline conditions.
Blood Sampling Regimen
During the acute hypoxemia protocol, descending aortic blood samples (0.3 ml) were taken using sterile techniques from the fetus at set time intervals to determine arterial blood gas and metabolic status (Fig. 1). Arterial blood gas and acid-base measurements were determined using a blood gas analyzer (model ABL5, Radiometer, Copenhagen, Denmark; measurements corrected to 39.5°C), percent saturation of Hb with O2 (Sat Hb) and blood Hb concentration ([Hb]) were determined using a hemoximeter (model OSM3, Radiometer), and blood glucose and lactate concentrations were measured by an automated analyzer (2300 Stat Plus Glucose/Lactate Analyser, Yellow Springs Instrument, Farnborough, UK). An additional 4 ml of arterial blood were withdrawn at set intervals for hormone analyses (Fig. 1). The samples were collected under sterile conditions into chilled heparin tubes (2 ml Li+/heparin tubes; LIP, Shipley, West Yorkshire, UK) containing reduced glutathione (4 nmol per tube; catalog no. G-4251, Sigma Chemical) and EGTA (5 nmol per tube; catalog no. E-4378, Sigma Chemical) for catecholamine (epinephrine and norepinephrine) analysis or into chilled EDTA tubes (2 ml K+/EDTA; LIP) for ACTH and cortisol analysis. All samples were centrifuged at 4,000 rpm for 4 min at 4°C. The plasma was dispensed into prelabeled tubes, and the samples were stored at −80°C until analysis. All hormone measurements were performed within 2 mo of sample collection.
Hormone Analyses
Catecholamine assay.
Fetal plasma epinephrine and norepinephrine concentrations were measured by HPLC using electrochemical detection, as previously described in detail (18). The samples were prepared by absorption of 250 μl of plasma onto acid-washed alumina, and 20-μl aliquots of the 100-μl perchloric acid elutes were injected onto the column. Dihydroxybenzylamine was added as the internal standard to each plasma sample before absorption. The limit of sensitivity for the assay was 20 pg/ml for epinephrine and norepinephrine. Recovery ranged from 63% to 97%, and all catecholamine values were corrected for their respective recovery. The interassay coefficients of variation (CV) for epinephrine and norepinephrine were 7.3% and 6.2%.
ACTH assay.
Fetal plasma ACTH concentrations were measured using a commercially available double-antibody 125I-RIA kit (DiaSorin, Stillwater, MN), as previously described (42). The kit contained a set of ACTH standards (porcine; range 20–500 pg/ml), ACTH quality control samples, lyophilized rabbit anti-ACTH antiserum, 125I-labeled synthetic ACTH, and a second antibody-precipitating complex (goat anti-rabbit γ-globulin serum and polyethylene glycol in buffer). Reagents were reconstituted in deionized water and kept on crushed ice. Duplicate 100-μl aliquots of the ACTH standards, quality controls, and unknown plasma samples (taken from previously unthawed K+/EDTA-treated plasma aliquots) were incubated overnight at 5°C with 200 μl of anti-ACTH antiserum and 200 μl of 125I-labeled ACTH. Bound and free ACTH fractions were separated by immunoprecipitation with the second antibody-precipitating complex (500 μl). After centrifugation (3,600 rpm for 20 min at 20–25°C), the supernatant was rapidly decanted and discarded, and the residue pellets were allowed to dry. A gamma scintillation counter (Cobra II Auto-Gamma, Packard Bioscience, Pangbourne, Berks, UK) was used to count the radioactivity of each pellet for 2 min, together with that of duplicate nonspecific binding samples (anti-ACTH antiserum omitted) and that of total-counts tubes (200 μl of 125I-labeled ACTH). A standard curve was produced by the computer using a logistic curve fit, and ACTH concentrations were calculated for each pellet.
The lower limit of detection of the assay (90% bound/free) was 10–25 pg/ml. The intra-assay CV for three plasma pools (mean concentration = 69, 281, and 600 pg/ml) were 12.5, 6.3, and 8.1%, respectively. The interassay CV for two plasma pools (mean concentration = 36 and 136 pg/ml) were 6.0 and 6.7%, respectively. The anti-ACTH antiserum showed <0.01% cross-reactivity against α-melanocyte-stimulating hormone, β-endorphin, β-lipotropin, leucine enkephalin, methionine enkephalin, bombesin, calcitonin, parathyroid hormone, follicle-stimulating hormone, AVP, oxytocin, and substance P.
Cortisol assay.
Fetal plasma cortisol concentrations were measured by RIA using [3H]cortisol as tracer, as previously described (20). Duplicate 20-μl plasma samples were taken from previously unthawed K+/EDTA-treated sample aliquots and extracted twice in 300 μl of ethanol. After each extraction, the aliquots were centrifuged and the ethanol layer was decanted into a bacteriological test tube. The combined ethanol extracts were evaporated in a drier (Speedvac Concentrator, SVC 200H, Stratech Scientific, Luton, UK) overnight. Residues were reconstituted in 100 μl of PBS (pH 7.0) and allowed to stand at 5°C for ≥2 h. Samples in which cortisol concentration values were predicted to be in the upper range of the standard curve were diluted using PBS to reduce the concentration to within the most sensitive range (1–10 ng/ml) of the standard curve. Values for these samples were subsequently corrected for the dilution factor used in each case. The plasma extracts, quality control samples, and working standards (1, 2.5, 5, 10, 25, 50, and 100 ng/ml) were incubated overnight (5°C) with 100 μl of antiserum (Tenovus Institute, Cardiff, UK) and 100 μl of [1,2,6,7-3H]cortisol (TRK407, Amersham Pharmacia Biotech UK, Little Chalfont, Bucks, UK). Bound and free cortisol fractions were separated using stirred dextran-coated charcoal suspension (300 μl, 0.075 g% dextran and 0.75 g% activated charcoal in PBS). After immediate centrifugation (3,600 rpm for 7 min at 4°C), the supernatant was rapidly decanted into scintillation vial inserts, and 4 ml of scintillant (OptiPhase HiSafe, Fisons Chemicals, Loughborough, UK) were added to each insert. The inserts were capped, and the contents were thoroughly mixed. After a 1-h equilibration period, a scintillation counter (1216 RackBeta Liquid Scintillation Counter, LKB Wallac) was used to count the radioactivity of each insert for 5 min, including the radioactive content of duplicate nonspecific binding samples (antiserum omitted) and total-counts tubes (100 μl of [3H]cortisol). Recoveries averaged 90%. A standard curve was produced by the computer using a spline curve fit, and cortisol concentrations were calculated for each sample.
The lower limit of detection of the assay was 1.0–1.5 ng/ml. The intra-assay CV was 5.3% for a mean value of 13 ng/ml. The interassay CV for two plasma pools (mean concentration = 13 and 28 ng/ml) were 13.6 and 11.4%, respectively. The cross-reactivities of the antiserum at 50% binding with other cortisol-related compounds were 0.5% for cortisone, 2.3% for corticosterone, 0.3% for progesterone, and 4.6% for deoxycortisol.
Data and Statistical Analyses
Values are means ± SE. Fetal arterial blood pressure, heart rate, femoral blood flow, femoral vascular resistance (FVR), umbilical blood flow, and umbilical vascular conductance were recorded continually at 1-s intervals using the computerized data acquisition system. The concentration of protons ([H+]) was calculated using the following equation: [H+] = 10−pH. The fetal arterial blood O2 content (mmol/l) was calculated as follows: {([Hb] × Sat Hb)/100} × 0.62, where [Hb] (g/dl) is the blood concentration of Hb, Sat Hb is the percent O2 saturation of Hb, and 1 mol of Hb (64,450 mol wt) binds 4 mol of O2. The contribution of O2 dissolved in plasma is regarded as negligible (21).
For the acute hypoxemia experiment, values for all arterial blood gas and metabolic variables are expressed at 0 (N0) and 75 (N75) min of normoxia, 5 (H5), 15 (H15), and 30 (H30) min of hypoxemia, and 30 (R30) and 60 (R60) min of recovery. Values for all endocrine variables are expressed at 0 (N0) and 75 (N75) min of normoxia, 15 (H15) and 30 (H30) min of hypoxemia, and 60 (R60) min of recovery. Summary measure analysis was applied to the serial cardiovascular data to focus the number of comparisons (34). The area under the curve was calculated at 30-min intervals (N1, N2, N3, H, R1, R2) for the absolute data and for the change from mean normoxic baseline data describing the hemodynamic responses. All measured variables were assessed statistically using a two-way ANOVA with repeated measures comparing the effect of time and treatment and interactions between time and treatment. Functional chemoreflex analysis was performed to assess the effects of acidemia on fetal cardiac and vasomotor chemoreflex responses. For this analysis, linear regression lines were plotted for the cardiovascular chemoreflex response of each fetus, and a comparison between the slopes was conducted according to Armitage and Berry (4). The relationship between parallel measurements of plasma concentrations of ACTH and cortisol in all individual fetuses was assessed using the Pearson product moment correlation coefficient test. The mean change in adrenocortical responsiveness to ACTH (gradient and intercept of the cortisol-ACTH relationship) was assessed statistically using Student's t-test for paired data.
Where a significant effect of time or treatment was indicated using an ANOVA with repeated measures, Tukey's post hoc test was used to isolate the statistical differences. For all comparisons, statistical significance was accepted when P < 0.05.
Fetal Arterial Blood Gas and Metabolic Status
Basal values for fetal arterial blood gas status and fetal concentrations of blood glucose and lactate were similar in all fetuses and were within the normal range for the Welsh Mountain sheep fetus at ∼125 days gestation (Table 1, Fig. 2). Infusion with saline had no effect on basal arterial blood gas or metabolic status, but it produced a significant decrease in fetal pHa with a corresponding increase in [H+] (−0.06 ± 0.01 and 0.74 ± 0.08 × 10−8, respectively, P < 0.05; Table 1). In all fetuses, acute hypoxemia induced significant falls in pHa, PaO2, Sat Hb, and O2 content and a significant increment in fetal [Hb] but did not change PaCO2 (Table 1). The magnitude of these responses was similar in all fetuses. The increment in fetal [H+] by the end of hypoxemia relative to the corresponding basal value at N75 in fetuses infused with heparinized saline was not significantly different from that in fetuses treated with acidified saline (0.92 ± 0.09 × 10−8 and 1.21 ± 0.11 × 10−8, respectively; Table 1). Acute hypoxemia during saline infusion induced significant increments in blood glucose (0.76 ± 0.25 mmol/l) and lactate (4.74 ± 0.40 mmol/l) concentrations (Fig. 2). Treatment with acidified saline significantly enhanced the glycemic response (2.08 ± 0.38 mmol/l) but had no significant effect on the lactic acidemic response (5.95 ± 0.95 mmol/l) to acute hypoxemia compared with saline-infused controls (Fig. 2). During recovery, pHa remained significantly depressed, and blood glucose and lactate concentrations were significantly elevated above basal values in all fetuses, whereas PaO2, Sat Hb, and [Hb] returned toward basal values (Table 1, Fig. 2).
Fetal Cardiovascular Responses to Acute Hypoxemia
Basal values for fetal arterial blood pressure, heart rate, femoral blood flow, and FVR were similar in all fetuses (Fig. 3). Infusion with saline or treatment with acidified saline had no effect on basal cardiovascular function (Fig. 3). Acute hypoxemia during saline infusion induced significant increments in fetal arterial blood pressure (8.8 ± 0.8 mmHg) and FVR (4.32 ± 0.91 mmHg·ml−1·min) and significant falls in fetal heart rate (−20 ± 3 beats/min) and femoral blood flow (−26 ± 3 ml/min; Fig. 3). Treatment with acidified saline had no effect on the pressor increment during acute hypoxemia (9.3 ± 2.1 mmHg); however, it significantly enhanced the magnitude of the changes from baseline in the femoral vasoconstrictor (10.68 ± 1.60 mmHg·ml−1·min) and bradycardic (−57 ± 10 beats/min) responses to acute hypoxemia (Fig. 3). Interestingly, there was a rebound hypertensive response in all fetuses treated with acidified saline during the first 15 min of recovery following the hypoxemic challenge (P < 0.05; Fig. 3). During recovery, all cardiovascular variables returned toward basal values in saline-infused controls. In contrast, in fetuses treated with acidified saline, all cardiovascular variables remained significantly elevated above or reduced below both basal and control values by the end of the experimental protocol (Fig. 3).
Basal values for umbilical blood flow and umbilical vascular conductance were similar in all fetuses: in saline-treated fetuses, umbilical blood flow was 196 ± 29 ml/min and umbilical vascular conductance was 4.02 ± 0.46 ml·min−1·mmHg−1; in acidified saline-treated fetuses, umbilical blood flow was 222 ± 30 ml/min and umbilical vascular conductance was 4.40 ± 0.40 ml·min−1·mmHg−1. Acute hypoxemia during saline infusion induced significant increments in fetal arterial blood pressure, umbilical blood flow (43 ± 9 ml/min), and umbilical vascular conductance (0.15 ± 0.22 ml·min−1·mmHg−1; Fig. 4). In marked contrast, treatment with acidified saline not only abolished the umbilical vasodilator response to acute hypoxemia, but it resulted in a significant decrement from baseline in umbilical vascular conductance during the challenge (−0.97 ± 0.28 ml·min−1·mmHg−1; Fig. 4). During recovery, umbilical blood flow and vascular conductance remained significantly elevated above basal values in saline-infused fetuses but returned toward basal values by the end of the experimental protocol in fetuses treated with acidified saline (Fig. 4).
Functional Chemoreflex
Acute hypoxemia reduced fetal PaO2 to a similar level in all fetuses during infusion with saline or acidified saline (Table 1). Within the first 15 min of the onset of acute hypoxemia, the fall in PaO2 was associated with a significant reduction in fetal heart rate and a significant increase in FVR in both groups. However, the nadir for fetal heart rate and the maximum increase in FVR during the first 15 min of hypoxemia were greater when fetuses were treated with acidified saline (−75 ± 7 beats/min and 12.48 ± 1.39 mmHg·ml−1·min) than when they were infused with normal saline (−35 ± 7 beats/min and 3.97 ± 0.99 mmHg·ml−1·min). Consequently, when individual values for heart rate and FVR were plotted against corresponding values for PaO2 during normoxia and the first 15 min of acute hypoxemia (data not shown), the slopes for all individual data points representing the cardiac (−7.0× vs. −2.8x) and femoral vasoconstrictor (1.2x vs. 0.3x) chemoreflex function were greater in fetuses during treatment with acidified saline than during infusion of normal saline (P < 0.05).
Fetal Endocrine Responses to Acute Hypoxemia
Basal values for fetal plasma concentrations of epinephrine, norepinephrine, ACTH, and cortisol were similar in all fetuses (Figs. 5 and 6). Infusion with saline or treatment with acidified saline had no effect on basal catecholamine concentrations or basal pituitary-adrenocortical function (Figs. 5 and 6). Acute hypoxemia during saline infusion induced significant increments from baseline in plasma concentrations of epinephrine (414 ± 89 pg/ml), norepinephrine (2,665 ± 353 pg/ml), ACTH (303 ± 70 pg/ml), and cortisol (11 ± 6 ng/ml; Figs. 5 and 6). Treatment with acidified saline resulted in a marked enhancement in the plasma epinephrine (10,412 ± 5,541 pg/ml), norepinephrine (9,474 ± 3,689 pg/ml), ACTH (572 ± 154 pg/ml), and cortisol (37 ± 2 ng/ml) responses to acute hypoxemia (Figs. 5 and 6). During recovery, plasma concentrations of all hormones returned toward basal values in all fetuses (Figs. 5 and 6).
Correlation analysis of paired plasma ACTH and cortisol values for all individual fetuses under basal and hypoxemic conditions during saline infusion (r = 0.62, n = 20, P < 0.01) or treatment with acidified saline (r = 0.79, n = 20, P < 0.01) revealed significant linear relationships (Fig. 7). Treatment with acidified saline did not affect the intercept or the slope of the steroid-peptide relationship compared with saline infusion (Fig. 7; P > 0.05), thereby suggesting no change in the set point or the sensitivity of the adrenal cortex to ACTH stimulation.
This study tested the hypothesis that fetal acidemia affects the fetal defense responses to acute hypoxemia by investigating the in vivo effects of acute fetal acidemia on the fetal cardiovascular, metabolic, and endocrine responses to acute hypoxemia in the late-gestation ovine fetus. The data support the hypothesis tested and show that acute acidemia had no effect on basal cardiovascular, metabolic, or endocrine function but markedly enhanced the bradycardia, femoral vasoconstriction, and metabolic and endocrine responses to acute hypoxemia in the fetus. In marked contrast, acute acidemia not only prevented the dilator response of the umbilical vascular bed to acute hypoxemia, but it also reversed the response to constriction. Greater carotid chemoreflex function and an enhanced increase in plasma catecholamines may contribute to the physiological mechanisms underlying the altered cardiovascular and metabolic responses to acute hypoxemia in acutely acidemic fetuses.
The fetal bradycardia and peripheral constrictor response to acute hypoxemia are established carotid chemoreflexes, since bilateral section of the carotid sinus nerves abolishes the reduction in heart rate and the initial increase in FVR during acute hypoxemia (5, 25). As the hypoxemic episode continues, catecholamines are released into the fetal circulation and act to maintain the peripheral vasoconstriction (30, 32). The origin of the increase in epinephrine and norepinephrine in fetal plasma during acute hypoxemia has been shown to be primarily from the fetal adrenal gland, inasmuch as adrenal demedullation completely abolished the rise in plasma epinephrine concentration and reduced the norepinephrine response to 10% of normal (31). Since a large component of the increase in total catecholamine output from the fetal adrenal gland during acute hypoxemia is mediated via activation of the splanchnic nerves (31), elevations in plasma concentrations of epinephrine and norepinephrine in the fetal sheep circulation are good indexes of increased sympathetic outflow during stimulated conditions.
Data in the present study show that acute acidemia enhanced the bradycardic and femoral vasoconstrictor response to hypoxemia, possibly by sensitizing the carotid chemoreflex. During hypoxemia, the glomus cells of the carotid body become uncoupled, leading to a decrease in their junctional conductance, which results in the release of transmitters toward the carotid sinus nerve sensory terminals (15). The junctional channel proteins between glomus cells are directly regulated by pH, with acidemia shown to increase their uncoupling (1). Hence, acute acidemia could sensitize the fetal carotid body, thereby promoting a greater increase in autonomic outflow for any given fall in PaO2. The enhanced bradycardic response to acute hypoxemia supports this notion, suggesting a greater vagal outflow in acidemic fetuses. Evidence of an enhanced increase in sympathetic outflow during acute hypoxemia in acidemic fetuses is derived from the marked augmentation of the plasma epinephrine and norepinephrine responses to acute hypoxemia. Similarly, Lewis and Sadeghi (33) demonstrated that acidemia significantly potentiated the magnitude of the plasma catecholamine response to acute hypoxemia in the ovine fetus in response to splanchnic nerve stimulation. In vitro studies using the rat adrenal medulla showed that acidemia can directly stimulate catecholamine secretion, in isolation (19) or as an additive effect with hypoxemia (41). The enhanced plasma catecholamine response to acute hypoxemia in acidemic fetuses may also act to maintain the greater overall peripheral vasoconstrictor response.
In marked contrast to the effects on the peripheral circulation, further data reported in the present study show that acute acidemia reversed the umbilical hemodynamic response to hypoxemia from dilatation to constriction. In a previous investigation of the effects of acute acidemia on basal cardiovascular and endocrine function in the ovine fetus, Wood and Chen (49) reported that infusion of acid into the fetal circulation increased fetal PaCO2. In the adult animal with spontaneous ventilation, arterial acidemia increases ventilation via reflex mechanisms, correcting any increase in PaCO2. However, in the fetus, gas exchange is controlled by alterations in umbilical-placental blood flow. Wood and Chen, therefore, concluded that the increase in fetal PaCO2 following acute acidemia in their study may represent failure of the umbilicoplacental vascular bed to increase flow to buffer this effect, but they did not measure umbilical blood flow. The results of our study support this prediction and confirm that umbilical vascular conductance not only fails to increase, but it actually decreases, during acute acidemia. The reduction of fetal pHa reported in the present study (an average of −0.05) was significantly less than that reported previously (−0.4) (49). The comparatively milder acidemia may not only explain the lack of an increase in fetal PaCO2 in the present study during basal conditions, but it also highlights how sensitive the umbilical vascular bed may be to increases in fetal catecholamine levels, outweighing any vasodilator effects during stressful conditions. Several studies have shown that the umbilical vasculature does constrict in response to adrenergic receptor stimulation (8, 53). Taken together, past and present evidence, therefore, suggests that fetuses compromised by acidemia may be at greater risk during acute hypoxemic episodes, whereby augmented stimulated plasma catecholamine responses in the fetus may compromise umbilicoplacental perfusion, triggering a vicious cycle.
Interestingly, although acute acidemia had no effect on the magnitude of the arterial blood pressure response to acute hypoxemia, there was a "rebound" hypertension at the beginning of the recovery period. During hypoxemia, the effects of increasing plasma catecholamine levels on the fetal heart are opposed by increased vagal discharge. The sudden increase in fetal arterial blood pressure during recovery in acidemic fetuses may result from the augmented catecholamine drive, in the absence of any vagal outflow, on fetal heart rate and cardiac output. Greater circulating levels of catecholamines will also require a longer duration for their metabolic disposition, thereby prolonging the duration of their effects, as demonstrated by the maintained elevation of fetal arterial blood pressure and femoral vasoconstriction throughout recovery in the acidemic fetus.
It is well established that activation of the sympathetic nervous system and an increase in circulating concentration of catecholamines are responsible for the fetal glycemic response to acute hypoxemia (3, 28). Data from the present study support this theory and show that although acute fetal acidemia had no effect on basal metabolic function and basal plasma catecholamine concentrations, it enhanced the glycemic and catecholaminergic responses to acute hypoxemia in the late-gestation fetus. However, since acidemia has been shown to also enhance glucose-stimulated insulin release (39), the overall effect of acidemia on fetal circulating glucose concentrations is likely to be partially offset by increased insulin release. In contrast to the glycemic response, acute fetal acidemia did not significantly affect the lactic acidemic response to acute hypoxemia, despite the elevated fetal peripheral vasoconstrictor response. This may be attributed to acidemia-enhanced uptake of lactate by various organs, as has been shown for the liver (45). In addition, the placenta can act as a major site of lactate clearance from the fetal circulation, especially during periods of adverse intrauterine conditions (26). This effect may be enhanced by acidemia, inasmuch as the reduction in umbilical arterial perfusion would slow the transit time of circulating lactate through the umbilicoplacental vascular bed, thereby favoring placental lactate uptake.
Previous studies have shown that acute acidemia in the late-gestation fetus stimulates the hypothalamus-pituitary-adrenal (HPA) axis under basal conditions, resulting in an increase in ACTH release from the pituitary and an increase in cortisol release from the adrenal cortex (49, 51). In contrast, results from the present study show that acute fetal acidemia had no effect on basal concentrations of plasma ACTH and cortisol. This difference may again be due to failure to attain the threshold of acidemia required to stimulate ACTH and cortisol secretion, since the degree of acidemia induced in fetuses in the present study was significantly less than that reported previously (49, 51). During acute hypoxemia, fetal acidemia markedly increased the magnitude of the plasma ACTH and cortisol responses, but it had no effect on the intercept or the slope of the steroid-peptide relationship, thereby demonstrating that there was no change in the set point or sensitivity of the adrenal cortical response to ACTH. This in agreement with previous studies that reported no effect of acidemia on ACTH-stimulated cortisol secretion (38). The sensitizing effects of acute acidemia on the fetal HPA axis may therefore be at the level of the hypothalamus and/or the pituitary. At the level of the hypothalamus, acidemia may increase the release of corticotropin-releasing hormone (CRH) and/or AVP, since both hormones have been shown to stimulate the release of ACTH from the fetal anterior pituitary (16, 52). Although there is no available evidence for an effect of acidemia on the release of hypothalamic CRH, Wood and Chen (49) reported that acidemia directly stimulates the release of AVP in fetal sheep, whereas Gardner and colleagues (20) showed a markedly enhanced AVP response to acute hypoxemia in spontaneously acidemic fetuses. Furthermore, since catecholaminergic neurons in the hypothalamus have been shown to be functional in the sheep fetus during late gestation under conditions of acute hypoxemic stress (35), it is possible that acidemia could increase the release of CRH from hypothalamic neurons by enhancing sympathetic activity (33). At the level of the pituitary, acidemia can directly stimulate the secretion of ACTH in the sheep fetus (51), but whether this is a direct effect on pituitary corticotroph cells or occurs higher up the axis remains unknown, and the mechanism mediating this effect in the adult appears different from that in the fetus. For instance, in the adult, but not the fetus, acidemia stimulates the release of ACTH via thromboxane (12, 13, 50).
Perspectives and Significance
The data in the present study show that acute acidemia markedly affects the fetal hemodynamic, metabolic, and endocrine responses to an episode of acute hypoxemia in the late-gestation ovine fetus. Components of these findings are of clinical relevance. For instance, spinal anesthesia is widely used in clinical practice, inasmuch as it is commonly considered to be more practical and safer than other techniques for the mother and unborn child (37). A recent meta-analysis concluded that spinal anesthesia induces fetal metabolic acidosis, an effect that is exacerbated by ephedrine when used to manage maternal blood pressure (40). Although acidemia enhances the fetal cardiovascular, metabolic, and endocrine defense to acute hypoxemic stress, the data in the present study show that acidemia and increased concentrations of catecholamines are associated with important constrictor effects on the umbilicoplacental circulations, particularly during fetal distress. These findings should be considered when planning the management of maternal anesthesia and when assessing cardiovascular indexes of fetal health, for instance, via Doppler blood flow velocimetry or fetal heart rate monitoring, in pregnancies with suspected fetal hypoxia and acidemia.
This work was supported by the International Journal of Experimental Pathology and the Lister Institute for Preventive Medicine.
We thank S. Gentle and S. Nicholls for invaluable help with animal maintenance and M. Bloomfield for help with the catecholamine analysis.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2009 the American Physiological Society


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There is a progression that young married couples often have; they get a dog, then decide to have a kid. Olivia Ma Corwin has made a similar leap with her business, Liv & Co.The designer started out making dog clothes and bags to carry small pets, and has now branched out into making diaper bags, onesies and accessories for babies — at the same time that she is having her first child.
The luxurious, fashionable diaper bags are made from leather, canvas, fake leather and patent leather.They look great, but are also designed with functionality in mind. The bags are lined in water-resistant nylon, good for soggy baby clothes or bottles, and have removable shoulder and stroller straps, giving mom more options. Each includes a matching changing pad, lots of pockets, and a detachable coin purse (which can double as an evening clutch).
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The new clothing line includes the sweet outfits that aunts and uncles often pick up for their nieces: tiny crocheted dresses, smocked pants, and ruched leggings. The soft baby blankets would look great tucked around an infant in his stroller.
Corwin plans to further expand the company to include vintage-inspired organic bedding.
Liv & Co. diaper bags and clothes are available at Coquette Kidswear, Z Baby Company, and Pumpkin, or at www.livandco.com.
Here's What You Need to Know About Smart Toy Safety
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text: Same as all the others, 3 days Retrieved from "http://answers.wikia.com/wiki/If_the_residents_of_underworld_become_hostile,_how_long_before_they_reset_to_friendly_will_they_reset?oldid=6765053" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Fallout series Answered questions Page titles not starting with an interrogative word Add category Cancel Save


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"ward 8"
Posted by Anonymous
Anything else?
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Toyota of Puyallup
Review for Toyota of Puyallup
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"close to home and consistent good service"
My service technician was friendly and helpful. Consistently over deliver on wait time. No prea sure sales staff.
Vehicle: SCION XD
Category: Service
Service Date: 01/19/2015
Review Created: 01/20/2015 06:28 PM


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Vogue 5029; ©1960; Suit Dress. Easy fitting jacket buttons below notched collar. Patch pockets. Below elbow length sleeves with buttoned trimmed extension tab. Two styles of skirt included in pattern - slim, straight and all around box pleated.
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JAPAN: Mitsubishi to enter Iran with CKD SUV assembly
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text: Home Inn (Shanghai Xujiahui University of Communications Yishan Road) is 6 km from Shanghai South Railway Station. The hotel boasts easy access to local attractions and airport. Free Wi-Fi and free parking lot are provided at the hotel. All rooms here are equipped with domestic direct-dial telephone, free toiletries, electric kettle, slippers, chairs, indoor washroom, indoor bathroom. Opened in 2011, the 5-storey hotel houses 100 rooms and suites.


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Agility Photos
Finally found some time to gather recent photos from agility trials, mostly by Maja, partly by Iztok, Jana, Monika, Janja - thank you all! I just love the agility photos because of all those intense expressions on their faces 🙂 Too cute!
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Work Support Pressure, and Mental Health in BuildingPosted by John C on Nov 9, 2014 in Mental Health | Comments Off on Work Support Pressure, and Mental Health in Building
Workplace Pressure
There's no one universally accepted definition of pressure. In the
Australia, for instance, the National Institute for Occupational
Health and Safety ?1999? defined work-related anxiety "as
The dangerous psychological and physical reactions that happen when the
Demands of the job don't fit the abilities, resources,
Or needs. Occupation strain can cause poor health and even
Harm." In The Sutherland Shire of NSW, Mental Health Commission of NSW see more here ?1999? Said "pressure is the reaction people have to excessive
pressures or alternative demands put on people." The Australian Government
Comcare ?2008? defined work-related anxiety as "a kind
Of stress, a state of arousal, and negative emotions experienced in
Relationship to the work function."
There exists a should come up with a better understanding of how
Pressure is experienced in the building industry, the procedures by
Which it may be minimized efficiently or ameliorated and the
Variables that predict why some professionals experience stressrelated
States? Edwards 2005 and Love?. A theory
provide some insight into these problems is the Lazarus and Folkman1984? theory of anxiety assessment. Lazarus ?1991? Supplied a conceptualization
of pressure that focused on work-related stress as a
Procedure, affecting a trade between a person and their
work environment. Based on Lazarus and Folkman ?1984?,
This pressure is cyclical and completely recursive in the results of
the pressure procedure ?strains? Possess the potential to affect future
Results by depleting the or by becoming added resources
Managing resources and skill supports that exist to the
Person. In conditions that are serious or constant, stress can lead
To mental ill health, which affects farther on anxiety and
Stress. Thus, pressure is a circular and always transforms
Procedure that consists of stressors ?i.e., the state that causes
Stress physically?, consequences, and resources, which raises important
Consequences for measurement and Treatment
Lazarus and Folkman ?1984? proposed the subjective assessment
by a person makes their scenario essential to their own wellbeing.
A scenario is unable to be considered trying until the
Person has identified it as such. Stressful conditions are
those appraised as threatening or dangerous to the person, and
those that the person considers they'll be unable to handle
or control. Thus tension resides in the man nor workplace,
but is a reflection of the individual's exceptional result to their
Conditions. In compliance with all the pressure-procedure definition,
Work pressure was described as an incompatibility
Person as well as their work environment which is perceived as trying
?Humphy 1998?.
The most critical stressors identified by building supervisors
have been work overload, role ambiguity and conflict, outstanding
Overtime the varied variety of prohibitive career advancement,
Characters encountered in their own work environment, traveling,
Shifting technology, redundancy, customer demands, small resources,
Fiscal pressures, budget solving little, and constraints
But pressing and Davidson and irksome issues?Sutherland
1989; CIOB 2006?. Based on Langford and Sommerville
?1994? the common factors behind anxiety may be categorized as the physical
environment, the organization the physical, the manner in which work in
Handled, the person's job the relationships together with the organization,
Inside the corporation, societal and private relationships,
Gear, and stress that is individual.


text:
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Upcoming events appear below as soon as they are confirmed.
As a club member, you receive discounted invitations to all paid club events. The club's operating budget, which enables us to sponsor events, relies on annual membership dues. Annual club dues support our club's student send off and provide scholarships to students from Western New York attending Syracuse University.
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SCHOLARSHIP PROGRAM: The Club has supported scholarships for outstanding SU students from Western New York area each year and support for these scholarships continues to grow. SUofWNY has two scholarship funds established for Syracuse University. Together, the Fred E. Machemer Scholarship Fund and the Buffalo Endowed Scholarship Fund help us provide nearly $10,000 each year to SU students from the Western New York area.
DONATE TO ONE OF OUR SCHOLARSHIP FUNDS: To request additional information or if you have any questions about our scholarship fund, please contact us at firstname.lastname@example.com. Thank You for your Support!
Syracuse University Alumni Club of WNY
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text:
sE Electronics sE5
- Description
- Additional Information
sE Electronics sE5 Product Description
Small Diaphragm Condenser Microphone With Free Custom Shockmount
Introducing the sE5, the newest small-diaphragm condenser microphone. We've taken the sE5's predecessor, the sE4, and redesigned it from the capsule right through to the chassis. sE5 sets the new standard for small diaphragm microphones at its price, and is perfect for studio and live use.
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Creating free ebooks Winston?
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|Better Cotton Initiative
The Better Cotton Initiative (BCI) is a voluntary program who's vision is to enable millions of farmers around the world to grow cotton in a way that is healthier for the farming communities and the environment, and more economical
BCI encourages the adoption of better management practices in cotton cultivation to achieve measurable reductions in key environmental impacts, while improving social and economic benefits for cotton farmers, small and large, worldwide.
This global multi-stakeholder initiative recognizes the wide array of issues connected to cotton cultivation, each of different importance depending on regional circumstances. In order to effectively address the key negative impacts of cotton cultivation, BCI will act on the most significant issues, within certain cotton growing regions, while striving for continuous improvement and expansion of its activities to additional regions over time.
BCI's approach is to define 'Better Cotton' by establishing global principles and criteria that are applied through regionally specific implementation strategies and tools. BCI will use regionally-based indicators to measure the impact of the implementation strategies and tools as well as the overall success of BCI.
BCI's philosophy is to develop a market for a new mainstream commodity, where the boundary of its work is at the farm gate. BCI will not directly address global policy & trade issues but focus on building capacity rather than policing. BCI is not designed with a product label in mind and is complementary to Certified Organic and Fairtrade cotton.
Currently BCI is governed by a Steering Committee comprising of 20 global organisations including, but not limited to, producer organisations, trade & industry organisations, civil society, and international institutions. Current participating organisations are Adidas, Gap Inc., H&M, ICCO, IKEA, Organic Exchange, Pesticide Action Network UK and WWF.
BCI will engage with all stakeholders that support BCI's vision and mission as part of the process to establish global principles and criteria for 'Better Cotton'.
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|Unico Hommes <un...@apache.org>
|Re: [vote] Give Max Pfingsthorn temporary and restricted commit privileges to our code repository
|Sun, 10 Jul 2005 12:44:34 GMT
-----BEGIN PGP SIGNED MESSAGE----- Hash: SHA1 Reinhard Poetz wrote: > > As you all know, Max Pfingsthorn is one of our Google Summer of Code > students and he will work on the implementation of the cforms library. > > In order to make his life and the life of his two mentors (Sylvain and > I) easier, I want to give him *temporary* and *restricted* > (http://svn.apache.org/repos/asf/cocoon/whiteboard/forms/**) commit > privileges to our SVN code repository. > > After the project Max' account will be closed and he has to go the usual > way of becoming a regular Apache Cocoon committer. > (http://www.apache.org/foundation/how-it-works.html#roles). > > Please cast your votes! > +1 - -- Unico -----BEGIN PGP SIGNATURE----- Version: GnuPG v1.4.1 (Darwin) iD8DBQFC0Rgxcuec8tVNKAwRAgYkAJ9igJOcqGEPfDeOrRlvhdzxsoO3BACgj5UQ y7XHv8DPnXiefGIN75LUOGI= =SDuL -----END PGP SIGNATURE-----
|View raw message


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My girlfriend and I are coming from Australia to see the Packers play on October 27 and Minneapolis and then against the Bears at Lambeau on November 4. We are spending the week in between at the Dells.
I love the idea of indoor water parks (we don't have anything like that in Queensland, Australia) and I really want to go to one. They all seem to be mad for children though. I was just wondering if you guys could give me advice on which park would be best to visit if you don't have children?
Also, any other suggestions for what we can do while we are there? We will be there for Halloween and I'm hoping there will be some festivities for this?
Thanks guys!!!


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Dec 12, 2009
Might be a repost but what the hell
If i had done that my wife would have got one of my shotguns and, well you cant make the rest up.
Haha, awesome.
Very funny although my wife didn't see the funny side.:icon_thumright:
Legend! that is fab.
haha, that's brilliant! I am going to try that. However, my wife is a bit of a sleep walker/ talker, and one night she thought I was another man in bed with her. She didn't kick me out of bed either, just wouldn't let me spoon her, haha! Maybe i should be worried about this?
Too funny man!
Na, I wouldn't worry.... It could of been worse!
How so??
She does some brilliant stuff in her sleep, she once jumped out of bed to catch a light which was falling from the ceiling. I was laid in bed laughing so hard at her. She has also got dressed for work a few times too.
Come to think of it, she thought I was someone else another time too. This time though she started texting me, getting all annoyed as I wasn't home from work yet (obviously I was as I was laid next to her, but she thought I was another man). She sent the text, and an "oh ****" was suddenly blurted out as she regained control of her brain and realised the foolishness!
Gotta love sleep-walkers/ talkers
Well, she could of thought you were another bloke AND let you spoon her....
I used to have a bird like that, I used to have to guide her back to bed when she was sleep walking. It was actually a pain in the ass to be fair
haha, that is a fair point, hadn't thought of it like that! Maybe one day she'll think i'm another woman and ravish me...that'd be awesome!
Haha, Wouldnt it just....
Separate names with a comma.


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Tuesday, June 02, 2015 4:33 pm
Even if a millennial has a long way to go to retirement, an annuity can still make sense.
Wednesday, May 13, 2015 3:36 pm
A 25-year-old who gives up one latte a day and saves the money for retirement will hit the jackpot.
Thursday, February 26, 2015 11:18 am
A new survey shows that young military members are positioning themselves for long-term personal finance success.
Thursday, October 16, 2014 6:30 pm
A new survey reveals some surprising findings about millennials and their banking preferences. Should big banks be worried?
Wednesday, July 16, 2014 4:05 pm
Workers younger than 35 are doing a remarkably good job of saving for retirement.
Thursday, June 20, 2013 6:11 pm
New research reveals some serious problems for young banking customers.


text:
Chicken Tortilla Soup
Recipe by Corkaline
The longer you let this one simmer the better it tastes and the better your house smells. This is great for a cold rainy day, or even a bad day (this is my comfort soup). This soup has helped me through a few rough weeks in the past year and I hope it can help you to.
Top Review by Heavens Kitchen
This is an interesting recipe. The ease and quickness of putting it together is what drew me to it in the first place. It is certainly easy to make. The flavors of the soup really do have to meld together before you can eat this, and even still, the gumbo soup flavor is definitely apparent. I thought the flavor of the soup was good, actually, and my family enjoyed it as well. Unfortunately, I probably wouldn't make this again unless I was able to find low-sodium versions of the ingredients.
See Discussion:1 Review
Ingredients Nutrition
- 2 (10 1/2 ounce) cans chicken gumbo soup
- 1 (10 ounce) can enchilada sauce
- 1 cup salsa (any brand)
- 4 cups chicken stock
- 1 chicken breast (chunked or shredded)
Directions See How It's Made
- Combine your chicken gumbo, enchilada sauce, salsa and stock.
- Cook and shred or chunk you chicken breast. *you can use canned chicken it works just as well and you can add more or less to your liking.
- Add chicken and let cook in a crock pot for at least 2 hrs *the longer the better.
- Serve up with shredded cheddar cheese and crushed tortilla chips. You'll love this for years to come.


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Laurel, MDUSA
January 5, 2012
Help support your Meetup
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Technologists, entrepreneurs, investors, government, or corporate employees are encouraged to join in this exciting and very promising world of open source cloud computing called OpenStack (http://openstack.org/). Let's OpenStack & learn together. We will be known as the OpenStackers.
Are you interested in deploying a Private, Community, Public and/or a Hybrid cloud in the Washington, DC metro area or do you just want to learn or teach? Then let's make this a possibility by participating and collaborating in meetups, presentations, installfests and possibly hackathons.
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Zigoton: The Game is the first game in the Zigoton (series). It will be released for the PSP and the DS on February 7th, 2011. It shows the story of Patapon from the Zigoton's side.
The gameplay is similar to the Patapon gameplay, only you can see the entire army over the battlefield. Your actions affect the Zigotons over the entire area. Here is the list of rhythms.
- ZigoZigoZigoTon (Move forward)
- TonTonZigoTon (Attack)
- DidileeDidileeZigoTon (Defend)
- TonZigoTonZigo(Retreat)
- Mira, MiraMira, MiraMira (Miracle)
- TonTonDidileeDidilee (Charge)
Mission 1 – Scouting in the Patapon Valley (Journey)
The Zigoton have been forever keeping the Patapon unmoving in the small valley below to prevent the Zigoton prophecy from unfolding. Today, two Hataton are going to the right of their posts to scan for strange occurrences. You simply go from right to left, using the Zigoton's two pianos (Zigo piano and Ton piano) to move. Soon after, you encounter some Patapon moving toward some old ruins. The pianos flip around and you must run away from them, as well as a big beast chasing after them all. You must run past the Obeliskian Ruins and back to your posts.
Mission 2 – Ruins of the General Chang (Journey)
You are again the two Hataton. In this mission, you are going through the fields to go report to General Chang the Chagaton. On the way you meet some Yariton. Use their attack powers to hunt. You then find four statues. You must do the rhythm printed on them 3 times on the first three statues to defeat them. The fourth statue is faded and will disappear when you get near. After the statues you get back to Zigoton Central.
- Mission 2B – Ruins of the Hunt (Hunting)
You can come here with an army at any time after beating Mission 2. It has the same map as Mission 2, only with more things to hunt and the only statue is the fourth one which still disappears.
- Mission 2C – Ruins of the Secret Fourth Statue (Journey)
This mission is playable once after acquiring the Didilee Piano. You play as the Hatatons and start next to the fourth statue. After playing the defense song as Helpaton suggests, the statue will spin around revealing a new rhythm. Play it five times and the statue will explode, revealing the Ancestral Compass. You win the level!
Mission 3 – Basin of the Patapon Borders (Army)
The Patapon are uprising! In this mission, you can see the entire battlefield and using ZigoZigoZigoTon will make the forces hop to the next battle station, not move forward. TonTonZigoTon works like normal. To win you must manage to hold of the forces long enough for a Hataton to report back to General Chang. After that, the Zigoton get backup and push the Patapon away.
Mission 4 – Battle for the Basin of the Patapon Borders (Army)
This mission plays similar to Mission 3, only there are more Patapon fighting. You must try to defeat as much of the Patapon army you can before they charge into a tower and get the soul of a legendary warrior. After this, General Chang shows up. You now control him moving past the Zigoton forces toward the Patapon to fight. You must then hold off the Patapon until the rest of the Zigoton have escaped. After that General Chang makes a sacrifice to save the Zigoton.
Mission 5 – War at the Basin of the Patapon Borders (Army)
In this level you play as Gong the Hawkeye, leader of the Zigoton. You must move towards the left past Zigoton towers, until you run into two legendary heroes. You then have to push them back with your whirlwind attack, used when you attack in Rage mode. Push them back until they lose their energy. The Patapon army will advance on you. Defeat half the army and you will get a message from you assistant, Helpaton. He says the Oasis area is ready for inhabitants. Time to journey there!
Mission 6 – Desert of the Didilee Piano (Beast)
In this mission, you play as a small army. In the beginning, you find the Didilee Piano and learn the Defense song, Didilee Didilee Zigo Ton. You soon run into a big beast, Nonnom. Nonnom is a large dinosaur-type creature with wings that only let it fly short distances. You must defeat it as it flaps around from place to place.
- Mission 6B – Flying Beast Nonnom Second Battle (Beast)
You can play this after beating Mission 6. It's another fight with Nonnom, only he has 1.2x health.
- Mission 6C – Flying Beast Nonnom Third Battle(Beast)
You can play this after beating Mission 6B. Nonnom has 1.5x health and does 1.2x damage from the original!
- Mission 6D – Flying Beast Nonnom Fourth Battle (Beast)
You can play this after beating Mission 6C. Nonnom has 2.0x health and does 1.3x damage from the original!
- Mission 6E – Demonic Flying Beast Demo-Nonnom(Beast)
You can play this after beating Mission 6D. Demo-Nonnom actually flies around a lot, only landing after you do enough damage. He spews demon fire which can lock Zigoton into a hypnotic state for a while. Defeating him gives you the Nonnom Essence, allowing you to create Nonnomton for use in armies (you can only put one Beaston in an army for an army level.)
- Mission 6F – Ruins of the Giant Flying Beast Zonnom (Beast)
You can play this after beating Mission 2C. Unless you bring the Ancestral Compass, it is empty. After you bring it, ruins will appear with Zonnom in it. Zonnom is only slightly stronger than Nonnom (about as strong as Nonnom's second battle). After beating Zonnom, you obtain the Calm Wind Flute.
- Mission 6G – Giant Flying Beast Zonnom Second Battle (Beast)
You can play this after beating Mission 6F. Zonnom has 1.2x health and does 1.2x damage than the original battle.
- Mission 6H – Giant Flying Beast Zonnom Third Battle (Beast)
You can play this after beating Mission 6G. Zonnom has 1.3x health and does 1.3x damage than the original battle.
- Mission 6I – Giant Flying Beast Zonnom Fourth Battle (Beast)
You can play this after beating Mission 6H. Zonnom has 1.5x health and does 1.5x damage than the original battle.
- Mission 6J – Giant Flying Demonic Beast Demo-Zonnom (Beast)
Demo-Zonnom has 2.0x the damage and health of Demo-Nonnom and has all of Zonnom's new moves. Beating him gives you the ability to recruit Zonnomoton in armies.
Mission 7 – Desert of the Constant Sandstorms (Journey)
You begin marching past basic desert terrain. Some Zigoton Towers will wave you through. Soon the sandstorms start. They will not allow you to pass and will slowly kill you unless you have brought the Calm Wind Flute. If you to, Helpaton will construct the Mira Piano. Play the Mira song Mira, MiraMira, MiraMira while in Rage mode with the Calm Wind Flute with you to unleash the Disaster Dance. Complete the dance to make a flute appear that will blow some calm winds in. You can now progress to the end.
- Mission 7B – Hunting in the Sandy Lands (Hunting)
You can play this mission after beating Mission 7. It is a basic hunting mission only with rarer animals. It is the same length as Mission 7, and there are no sandstorms or Zigoton Towers, only the ruins. It appears they have been demolished by Patapon!
Mission 8 – The Oasis Gate (Army)
The Zigoton are currently sending out scouts to scout the oasis while a small camp is posted right outside. Suddenly, the Patapon come, crossing the desert, making it rain! The Zigoton have a harder time seeing units to attack in the rain, and can use the Calm Wind Flute to blow the clouds away for a small amount of time. Hold off the Patapon until it is safe to enter the oasis!
Mission 9 – The Dried-Up Dondon Basin (Journey)
In this mission you have to scout the area for Patapon. There are not any. Then the pianos flip and you have to bring Zigoton to their stations in case the Patapon do decide to visit.
Mission 10 – Box of Enlightenment (Journey)
The newborn Zigoton children were chosen to enter the Box of Enlightenment and learn about the Zigoton prophecy. However, it appears they have not returned. One of the two Hataton decides to bring a small army into the box. After journeying around a bit, a voice from deep within the room stirs, blasting the army. The Hataton, the only survivor, is relayed the prophecy and told that he shall one day unleash this beast from his prison. The Hataton disagrees, but the beast forces him to or die. The Hataton is also told he must tell nobody else about this.
workin' on it...


text:
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irTactical Products Now CE Certified
The complete line of tactical training equipment from irTactical is now CE certified. CE certification, or European Conformity, is the European Union's approval of consumer products. This is similar to the FCC in the United States. This certification allows all iCOMBAT systems to be more easily sold and used throughout Europe and other places in the world.
In addition to the CE certification, irTactical equipment is categorized as a non-ITAR product and non-gun by the ATF. The combination of these certifications allows irTactical to grow very easily around the world and provides peace of mind to business owners and other buyers.
ETU – Elite Tactical Unit featuring irTactical
The irTactical Training system for police and security forces in action
The US TV-show "ETU – Elite Tactical Unit" by the Outdoor Channel shows the battle between several SWAT teams. They are supposed to solve problems during the show to win a larger amount of money in the end.
In all the shows (except from the first one) the irTactical training system is used to create the most realistic situations and training for the teams. In the excerpt er are showing her the SWAT teams need to enter a restaurant where an active shooter is threatening the guests. The victims inside the restaurant wear irTactical vests as well – so any shot hostage is exactly identified by the system and gives negative points to the teams.
Such trainings are normally hard to implement in the daily business of police and security forces as the police and others are training with paint-ammo in general. This is why the training normally takes place in special places – built to be trained in. Some of these places have almost nothing in common with real scenarios. When using the irTactical Trainings system you can train literally anywhere as this systems does not leave marks, needs no protection and is set up easily.
Also you can decide to use it as a game – everything is possible..


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My Librarian: Craig Graziano
My booklists | My reviews & blog posts
Growing up in the Fredericksburg area, I adored visiting the public library. The Salem Church Branch opened when I was in third grade. My mom picked my sister and me up from school. Watching the odometer, we cheered as we pulled into the parking lot. "Only 1.3 miles!"
It was an escape, a chance to learn more about what we were interested in or to discover something completely new. I was hooked, tearing through comic books, science fiction, and anything with a wicked streak of humor. Plus, there was a fantastic selection of movies and music. I dove right in and began working at Salem Church in high school.
While earning a B.A. in English from the University of Mary Washington, I listened to much of my required reading while shelving books at the Headquarters Library. Audio books do count...but only if you're paying attention! I earned an MLIS from the University of Pittsburgh and made it back just in time for our England Run Branch to open. I love books for every age level, whether it is a zany picture book, an angst-ridden young adult novel, or a great biography. If I like it, you'll probably hear about it from me sooner or later.
See what I'm reading | Check out all the My Librarians
Recent Booklists
Reviews & Blog Posts
"We've come because of the baby," she said. "We've come to help."
The Nest appeared soon after Steve's baby brother came home from the hospital, hanging from the eaves of the roof. Steve did not know exactly what was wrong with his new sibling, but he overheard his parents use words like "poor prognosis" and "degenerative." It was not long until Steve saw the wasps in his yard . . . and in his dreams.
"Horrible Bear!" shouts a girl after her kite is destroyed by a slumbering beast. It was not intentional. Bear simply rolled over in his sleep, and the kite went CRUNCH!
This red-haired young lady is fuming though. She stomps back to her house, yelling the phrase over and over. Bear figures if he is going to be blamed for an accident, then maybe he should do something really horrible.
Robo-Sauce is a strange and wondrous concoction. Its neon-orange glow hints at limitless possibilities. Oh, you've never had the pleasure of seeing this extraordinary mixture in action? Well, prepare to be robotomized!


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Interactive Art Director 2010 Stockholm student group Lap of Luxury consists of Swedes Kenneth Larsen, Simon Schlyter, Maira Serra from Spain, and Sougwen Chung from Canada.
The group is currently working on cutting-edge social media concepts for furniture giant, IKEA.
To follow the group's progress as well as daily task challenges as a group, such as the video below, visit:
http://lapofluxury.tumblr.com/ - or follow them on Twitter.
Monday, October 12, 2009
Right now at Hyper Island: Interactive Art Director students' blog
Upplagd av Hyper Island kl. 3:45 PM
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This property is no longer available.Search for Available Property.
34.7 acres in Fauquier County, Virginia
Charming old farm house situated on gorgeous rolling land with large pond, scenic vistas and lots of privacy. House has 3 bedrooms, large living room, dining room, kitchen and deck. Barn has huge loft upstairs that could be apartment or studio. Perfect property for vineyard, traditional farm, weekend retreat or family home. Diamond in the rough with many opportunities!
From Warrenton: 211 West to Right on 688 (Leeds Manor Rd), approx. 6 miles to property on right.
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NOTE: The information contained herein is provided as general information only and has been obtained from sources deemed reliable. It is provided without any guaranty, warranty or representation, expressed or implied, made by Lands of America, or any related entity, as to the accuracy or completeness of the information. The information is presented subject to errors, omissions, change of price or conditions, prior sale or withdrawal without notice. Prospective purchasers should make their own investigations, projections and conclusions concerning the information.


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Doctor insights on:
Reasons For Colon Cancer
If a colon needs to be removed because of colon cancer are their alternatives to a external bag?
Bag is rarely needed: Colostomy( external bag ) is rarely needed for elective cancer surgery. It is more frequently used if the cancer is located very close to the anus, Also, a temporary colostomy may be used for emergency surgery when cancer is obstructing colon completely and the bowel cannot be cleaned prior to the surgery. ...Read moreSee 1 more doctor answer
Cancer (Definition)
Cancer is a group of diseases that is characterized by uncontrolled cell growth leading to invasion of surrounding tissues that spread to other parts of the body. Cancer can begin anywhere in the body and is usually related to one or more genetic mutations that allow normal cells to become malignant by interfering with internal cellular control mechanisms, such as programmed cell death or by preventing ...Read more
Could you tell me what is the reason behind colon cancer?
Colon cancer: Colon cancer is a result of interaction between genetic factors and environmental factors, resulting in an abnormal and uncontrolled proliferation of gut cells. Environmental factors include diet, alcohol, smoking, certain bacterial infection, etc. Genetic change include mutations in tumor suppressor genes and dnr repair genes, both of which normal safeguard out genome. ...Read more
How do I find out what is the reason behind colon cancer?
Mostly unknown: Most colon cancers start as polyps. A minority of the colon cancers are hereditary and the cause is not known in most. Risk factors including low fiber diet, intake of saturated fats, obesity and increasing age. See this site for more info. http://www.mayoclinic.com/health/colon-cancer/ds00035. ...Read more
Is metastic colon cancer cause of enteritis ? Or would there be Another reason ?
Something else: Most likely something else, like a viral infection or reaction to chemotherapy. It's a complex situation however, so it's difficult to give much more info based on limited information. Hope this helps! ...Read more
How likely is colon cancer in a 15 year old girl? My daughter keeps thinking she has it for some reason What about are the chances?
Very very rare: Other for congenital situations colon cancer under 30 yrs of age is rare. Under 20 years of age is even rarer. The polyoma virus that initiates many of the cases requires a series of steps including the development of telomerase to initiate the malignant transformation process with mutation in p53 and the APC gene taking place. This takes years and why colon cancer appears at middle age. ...Read moreSee 2 more doctor answers
If i've been told there's a pretty good chance I have colon cancer would that be the reason when i go to the restroom that my legs always go numb?
Maybe: First off, if you've been told you probably have colon cancer, check it out right away, get treated. Numbness after going to the restroom suggests you are sitting in one position too long. This can occur if you have a partial blockage from a cancer which makes it hard to eliminate the feces. It could also be totally unrelated perhaps some spinal problem. As always, let your physician evaluate. ...Read more
What is colon cancer?
Cancer of the colon: Cancer that forms in the tissues of the colon (the longest part of the large intestine). Most colon cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids). There are estimated 103, 170 (colon); 40, 290 (rectal) new cases and 51, 690 (colon and rectal combined) deaths from colon cancer in us in 2012. Screening with colonoscopy started at age of 50. ...Read moreSee 2 more doctor answers
What is colon cancer?
Cancers: Cancers are abnormal, rapidly growing cells that do not know when to stop growing. These abnormal cells can damage local tissues, can attach to nearby organs or structures, can spread to lymph nodes, or can spread to other organs through the blood stream. Their growth damages what they are attached to, and often cancers encourage new blood flow to themselves. Cancer can grow in the colon. ...Read moreSee 1 more doctor answer
Colon cancer any signs?
Not always: Colon cancer tends to not have any signs or symptoms when it is early (when it is easiest to treat). That is why screening colonoscopies are so important, to remove any polyps that may become cancer, and to directly look for cancers. Colon cancer can cause bleeding from the rectum, tiredness from anemia, stool changes, or abdominal pain. Other things can cause this too. Best to be seen if ?S. ...Read moreSee 1 more doctor answer
Does colon cancer hurt?
Usually not: Early stages of colon cancer often have no symptoms. Colon cancer has long developmental stages starting out as polyps and can take yrs to develop, hence screening colonoscopy is done every 10 yrs for normal folks. Polyps can be removed during colonoscopy. Advanced cancer can cause pain by obstructing bowel, spread to liver, bone, brain, lung etc. See doc regulalry. Good luck. ...Read moreSee 2 more doctor answers
Colon Cancer (Definition)
Final few yards of your intestine, between the terminal ileum (small bowell) and rectum. It squeezes water and solidifies waste to stool. It is subject to outpouching (divertics) polyps, and these can become cancers. The cells are abnormal, invade into the muscle and travel ...Read more
Colon (Definition)
The colon is another term for the large intestine. This is the final portion of the digestive system, responsible for absorbing water and storing stool before evacuation. It is divided into sections described as cecum; ascending, transverse, descending and ...Read more


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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
Date Field>>Properties>>Time>>Time Format: The 24 hours format is not correct.Asked by 45mip19lot on February 19, 2017 at 10:12 AM
Your date format 24 hour in the drop down menu is wrong.
In the current design, if you select 24 hour format, the drop down options list 0-9 as a single digit.
This causes confusion because the 24 hour format is designed to stop any ambiguity between am and pm.
For example:
4 oclock in the afternoon is displayed as 16:00 & 4 0clock in the morning should be displayed as 04:00
12 hour format is 4:00am & 4:00pm
Your 24 hour format displays the early morning hours as 4:00, 7:00 etc, which to the untrained eye could be perceived as 4pm, 7pm etc
To correct this, you need to add a zero to the am digits.
Thanks, Mike
JotForm Support
Thanks for letting us know, I have forwarded this to our back-end team.
JotForm Developer
Hello Mike,
Thanks for the feedback!
Time format confusion is now fixed, please check it and let me know if you need anything further.
Thank you.