The effect of sodium bicarbonate on the flow-dependency of urinary prostaglandin excretion in man

1986 ◽  
Vol 70 (2) ◽  
pp. 141-145 ◽  
Author(s):  
J. Haylor ◽  
C. J. Lote ◽  
A. Thewles
Keyword(s):  
Sodium Bicarbonate ◽  
Excretion Rate ◽  
Human Subjects ◽  
Fold Increase ◽  
Urine Flow ◽  
Urine Ph ◽  
Healthy Human ◽  
Significant Difference ◽  
Fluid Load ◽  
Control Study

1. The influence of oral water loading on the excretion rate of prostaglandin (PG) E was investigated in healthy human subjects in a control study where the urine was acidic (pH 5.7) and after oral sodium bicarbonate, which made the urine mildly alkaline (pH 7.2). PGE was immediately extracted from urine and measured by a radioimmunoassay technique. 2. After sodium bicarbonate (5 g) the urinary PGE excretion rate was some three-fold higher (P < 0.01) than in the control study, in the absence of any significant difference in the urine flow (approximately 80 ml/h). 3. In the control study (urine pH 5.7) the urinary PGE excretion rate increased significantly (P < 0.01) as the urine flow rose in response to the oral fluid load. However, after sodium bicarbonate, PGE excretion did not alter after the fluid load despite a 10-fold increase in urine flow. 4. Since after bicarbonate administration PGE excretion is independent of urine flow, mildly alkaline urine may represent a condition under which renal PGE synthesis can be effectively assessed from measurements of urinary PGE excretion, in the presence of changes in urine flow. 5. In addition, the results are compatible with the hypothesis that, in man, PGE may be passively reabsorbed in the distal nephron, and a reduction in this reabsorption could contribute to or be responsible for the dependency of the excretion rate of PGE on urine flow.

BICARBONATE EXCRETION DURING HYPOTHERMIA

1963 ◽  
Vol 41 (1) ◽  
pp. 91-96 ◽  
Author(s):  
G. S. Kanter ◽  
R. H. Lubinski ◽  
I. M. Mielens
Keyword(s):  
Rectal Temperature ◽  
Plasma Levels ◽  
Excretion Rate ◽  
Artificial Respiration ◽  
Urine Flow ◽  
Urine Ph ◽  
Urinary Ph ◽  
Arterial Ph

The investigation was designed to determine whether the renal loss of bicarbonate contributes significantly to the acidosis of hypothermia. The excretion of bicarbonate during hypothermia was studied in five infused (6% creatinine in saline at 0.4 ml/minute) and five non-infused dogs. All animals were anesthetized and artificial respiration was not used. The rectal temperature was gradually reduced to the 26–27 °C range by approximately 4 hours of exposure to ice packing. After control, clearance periods of 30 minutes' duration were conducted serially and continually through the experiment. There was no significant increase in bicarbonate excretion during hypothermia in the non-infused group. The urinary pH remained at control levels of about 6.2. The fall in arterial pH was not due to urinary bicarbonate loss. The urinary pH in the infused group, which had a higher urine flow, increased to pH 6.7 due to increased excretion of bicarbonate. The urine pH in three animals with highest urine flows in this latter group approached plasma levels. The excretion rate of bicarbonate in the infused group, however, was similarly insufficient to account for the decrease in arterial pH. The hypothermic kidney is quite effective in reabsorbing bicarbonate.

BICARBONATE EXCRETION DURING HYPOTHERMIA

1963 ◽  
Vol 41 (1) ◽  
pp. 91-96 ◽  
Author(s):  
G. S. Kanter ◽  
R. H. Lubinski ◽  
I. M. Mielens
Keyword(s):  
Rectal Temperature ◽  
Plasma Levels ◽  
Excretion Rate ◽  
Artificial Respiration ◽  
Urine Flow ◽  
Urine Ph ◽  
Urinary Ph ◽  
Arterial Ph

The investigation was designed to determine whether the renal loss of bicarbonate contributes significantly to the acidosis of hypothermia. The excretion of bicarbonate during hypothermia was studied in five infused (6% creatinine in saline at 0.4 ml/minute) and five non-infused dogs. All animals were anesthetized and artificial respiration was not used. The rectal temperature was gradually reduced to the 26–27 °C range by approximately 4 hours of exposure to ice packing. After control, clearance periods of 30 minutes' duration were conducted serially and continually through the experiment. There was no significant increase in bicarbonate excretion during hypothermia in the non-infused group. The urinary pH remained at control levels of about 6.2. The fall in arterial pH was not due to urinary bicarbonate loss. The urinary pH in the infused group, which had a higher urine flow, increased to pH 6.7 due to increased excretion of bicarbonate. The urine pH in three animals with highest urine flows in this latter group approached plasma levels. The excretion rate of bicarbonate in the infused group, however, was similarly insufficient to account for the decrease in arterial pH. The hypothermic kidney is quite effective in reabsorbing bicarbonate.

Effect of imprime PGG on innate immune-activating pharmacodynamic changes in a phase I clinical study in healthy human volunteers.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 33-33 ◽  
Author(s):  
Nandita Bose ◽  
Nadine Ottoson ◽  
Ben Harrison ◽  
Jamie R. Lowe ◽  
Mark Matson ◽  
...  
Keyword(s):  
B Cells ◽  
Checkpoint Inhibitors ◽  
Human Subjects ◽  
Fold Increase ◽  
Innate Immune ◽  
Marker Genes ◽  
Beta Glucan ◽  
Healthy Human ◽  
Activation Markers ◽  
Pre Treatment

33 Background: Imprime PGG (Imprime) is currently in clinical development as combination therapy with checkpoint inhibitors. Imprime, a yeast-derived, soluble β-1,3/1,6 glucan is a Pathogen Associated Molecular Pattern (PAMP) that complexes with endogenous anti-beta glucan antibodies (ABA) and activates innate immune effector cells to trigger the anti-cancer immunity cycle. In this study, we sought to investigate the immunopharmacodynamic (IPD) responses of Imprime in healthy human subjects. Methods: Group 1 (n=12) received a single IV infusion of Imprime 4 mg/kg, Group 2 (n=12) received three weekly infusions of 4mg/kg Imprime. Group 3 (n=12) received infusions of 4 mg/kg or 2 mg/kg Imprime on weeks 1, 2 and 5. In groups 1 and 2, six subjects each received premedication with diphenhydramine 50 mg IV and dexamethasone 8 mg IV. IPD changes were measured at various times before, during and after Imprime administration. Results: Peak levels of complement activation products, C5a and SC5b-9 were detected at the end of infusion (EOI). A 2 to 3-fold increase in neutrophil and monocyte numbers were seen 4 hours post-Imprime infusion. Chemokines, especially IL-8 and MCP-1, were consistently detected at EOI. Cellular analyses showed Imprime binding to neutrophils, monocytes, subsets of DC and B cells. 24 hrs after EOI, a population of intermediate monocytes expressing higher levels of the activation markers CD86, PD-L1, and HLA-DR, was observed. Approximately one week post-Imprime, increased switched memory B cells and plasmablasts were detected. Consistent increase in expression of innate immune activation marker genes was evident as well. A substantial drop in free ABA and a concomitant increase in circulating immune complexes were seen at the EOI. Adverse events (AE) were limited to infusion related reactions. Importantly, the IPD changes and the AE were seen in subjects with higher ABA levels. The effect of pre-medications on some of the IPD will also be presented. Conclusions: These human data provide the first evidence linking pre-treatment ABA levels and Imprime IPD, substantiating the use of these pre-treatment ABA levels for patient selection.

Abstract 109: Aerosol Generation During Chest Compression and Defibrillation in a Swine Cardiac Arrest Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Cindy H Hsu ◽  
Mohamad H Tiba ◽  
Andre Boehman ◽  
Brendan M McCracken ◽  
Danielle C Leander ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Chest Compression ◽  
Respiratory Infections ◽  
Human Subjects ◽  
Healthy Human ◽  
Aerosol Generation ◽  
Significant Difference ◽  
Nose Cone ◽  
Ca Model ◽  
Particle Sizer

Introduction: Respiratory infections can occur through the transmission of virus-containing aerosols from infected individuals. It remains unclear whether cardiac arrest (CA) resuscitation generates aerosols that have the potential to transmit diseases including COVID-19. Hypothesis: In a swine CA model, chest compression and defibrillation generate aerosols (≤10 μm) that could contain respiratory viruses. Methods: To simulate witnessed CA with bystander-initiated CPR, 3 female non-intubated swine underwent 4 minutes of untreated ventricular fibrillation CA followed by ten 2-minute cycles of mechanical chest compression and defibrillation without ventilation. The diameter (0.3 - 10 μm) and quantity of aerosols generated during 45-second intervals of no-flow, chest compression, and after each defibrillation were collected via a nose cone by the TSI Optical Particle Sizer. Aerosol generated from the coughs of 4 healthy human subjects were also compared to the swine data. Results: There was no significant difference between the total aerosols generated during chest compression compared to no-flow. In contrast, defibrillation followed by chest compression generated significantly more aerosols than chest compression or no-flow alone (72.4 ± 41.6 x10 4 vs 12.3 ± 8.3 x10 4 vs 10.5 ± 11.2 x10 4 ; p < 0.0001), particularly at the larger-sized aerosols. Two consecutive human coughs generated 54.7 ± 33.9 x10 4 aerosols with a size distribution much smaller than post-defibrillation CPR (Table). Conclusion: Chest compression generated comparable aerosols to no-flow in a swine CA model. In contrast, defibrillation followed by chest compression generated significantly more aerosols than chest compression or no-flow alone, with a distribution shift toward larger aerosols. Additional research is needed to elucidate the mechanisms by which aerosol generation during chest compression is modified by defibrillation and to assess rescuer risk during CA resuscitation.

scholarly journals Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial

2011 ◽  
Vol 108 (2) ◽  
pp. 315-326 ◽  
Author(s):  
Inger Ottestad ◽  
Gjermund Vogt ◽  
Kjetil Retterstøl ◽  
Mari C. Myhrstad ◽  
John-Erik Haugen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Fish Oil ◽  
Human Subjects ◽  
Controlled Study ◽  
Healthy Human ◽  
Significant Difference ◽  
Healthy Human Subjects ◽  
Markers Of Oxidative Stress ◽  
Randomised Controlled

Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18–50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g/d of fish oil (1·6 g/d EPA+DHA; n 17), 8 g/d of oxidised fish oil (1·6 g/d EPA+DHA; n 18) or 8 g/d of high-oleic sunflower oil (n 19). Fasting blood and morning spot urine samples were collected at weeks 0, 3 and 7. No significant changes between the different groups were observed with regard to urinary 8-iso-PGF2α; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and α-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA+DHA was observed in both fish oil groups, but no significant difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short-term effects in healthy human subjects.

scholarly journals Metabolic Origin of Bold Signal Fluctuations in the Absence of Stimuli

2008 ◽  
Vol 28 (7) ◽  
pp. 1377-1387 ◽  
Author(s):  
Masaki Fukunaga ◽  
Silvina G Horovitz ◽  
Jacco A de Zwart ◽  
Peter van Gelderen ◽  
Thomas J Balkin ◽  
...  
Keyword(s):  
Resting State ◽  
Human Subjects ◽  
Blood Oxygen Level Dependent ◽  
Brain Regions ◽  
Breath Holding ◽  
Metabolic Demand ◽  
Blood Oxygen Level ◽  
Healthy Human ◽  
State Activity ◽  
Significant Difference

Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging studies have shown the existence of ongoing blood flow fluctuations in the absence of stimuli. Although this so-called ‘resting-state activity’ appears to be correlated across brain regions with apparent functional relationship, its origin might be predominantly vascular and not directly representing neuronal signaling. To investigate this, we simultaneously measured BOLD and perfusion signals on healthy human subjects ( n = 11) and used their ratio (BOLD/perfusion ratio or BPR) as an indicator of metabolic demand. BPR during rest and sleep was compared with that during a visual task (VT) and a breath-holding task (BH), which are challenges with substantial and little metabolic involvement, respectively. Within the visual cortex, BPR was 3.76 ± 1.23 during BH, which was significantly higher than during the VT (1.76 ± 0.27) and rest (1.56 ± 0.41). Meanwhile, BPR values during VT and rest were not significantly different, suggesting a similar metabolic involvement. Eight subjects showed stage 1 and 2 sleep, during which temporally correlated BOLD and perfusion activity continued. In these subjects, there was no significant difference in BPR between the sleep and waking conditions (1.79 ± 0.54 and 1.66 ± 0.67, respectively), but both were lower than the BPR during BH. These data suggest that resting-state activity, at least in part, represents a metabolic process.

Urine pH and the relationship between urine flow and urinary prostaglandin E excretion in the rat

1986 ◽  
Vol 108 (2) ◽  
pp. 247-253 ◽  
Author(s):  
J. Haylor ◽  
C. J. Lote
Keyword(s):  
Sodium Bicarbonate ◽  
Ammonium Chloride ◽  
Urine Flow ◽  
Low Flow ◽  
Common Mechanism ◽  
Prostaglandin E ◽  
Urine Ph ◽  
Alkaline Urine ◽  
Flow Dependency ◽  
The Relationship

ABSTRACT The relationship between urine flow and urinary prostaglandin E (PGE) excretion was investigated at constant urine pH in the anaesthetized rat. The urine pH was maintained at approximately pH 6 or pH 8 by the intravenous infusion of either ammonium chloride or sodium bicarbonate respectively. Two distinct patterns in the relationship between PGE excretion and urine flow were observed. The first showed a fall in urinary PGE excretion as the urine flow increased over the low flow range of 2–5 ml/h, and was common to both experiments. The second relationship, however, showed a marked difference between the ammonium chloride and sodium bicarbonate experiments since: (a) in acidic urine (pH 6), PGE excretion increased (P < 0·002) with the urine flow, attaining a rate of 87± 6 pmol/h (n = 6) at the highest level of flow achieved (12 ml/h); (b) in alkaline urine (pH 8), PGE excretion was significantly (P < 0·01) higher but did not increase with urine flow, remaining constant at approximately 90 pmol/h (n = 6). The lack of any additive effect on urinary PGE excretion between increasing the urine flow and making the urine alkaline may be explained by both stimuli acting through a common mechanism, a concept which is consistent with the hypothesis that PGE may be reabsorbed in the distal nephron. The flow-dependency of urinary PGE excretion could therefore result from a reduction in reabsorption rather than the increase in passive secretion proposed previously. In addition, PGE excretion in alkaline urine may be a more appropriate index of renal PGE synthesis, since above a urine pH of 7·5 its excretion is independent of both urine pH and urine flow. J. Endocr. (1986) 108, 247–253

scholarly journals Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol

2020 ◽  
Vol 7 ◽  
Author(s):  
Rossana Giulietta Iannitti ◽  
Alessandro Floridi ◽  
Andrea Lazzarini ◽  
Alice Tantucci ◽  
Roberta Russo ◽  
...  
Keyword(s):  
Animal Model ◽  
Water Solubility ◽  
Simulation Analysis ◽  
Human Subjects ◽  
Fold Increase ◽  
Pharmacokinetic Profile ◽  
Maximum Plasma ◽  
Healthy Human

Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo, due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.

Cardiorenal-endocrine responses to head-out immersion at night

1986 ◽  
Vol 60 (1) ◽  
pp. 176-183 ◽  
Author(s):  
K. Shiraki ◽  
N. Konda ◽  
S. Sagawa ◽  
J. R. Claybaugh ◽  
S. K. Hong
Keyword(s):  
Cardiac Output ◽  
Plasma Renin Activity ◽  
Creatinine Clearance ◽  
Response Pattern ◽  
Excretion Rate ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Urine Flow ◽  
Identical Response

Cardiorenal-endocrine responses to 3-h head-out immersion (HOI) (water temperature = 34.5 +/- 0.5 degrees C) were studied during day (0900–1400 h) and night (2300–0400 h) in six hydropenic male human subjects. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude during the day compared with night (P less than 0.05). Na excretion and osmolal clearance (Cosm) also followed the identical response pattern as urine flow, and in fact, the HOI-induced diuresis was entirely accounted for by the increased Cosm. Endogenous creatinine clearance was not different between the day and the night and remained unchanged during HOI. Both plasma renin activity and aldosterone concentration and urinary aldosterone excretion were nearly twofold greater during the day compared with night before HOI but decreased to the same level during HOI in both daytime and the nighttime series (P less than 0.05). There was no correlation between the Na excretion rate and renin-aldosterone levels either before or during HOI. Plasma antidiuretic hormone (ADH) level was comparable between day and night before HOI and decreased to a similar level during HOI in both daytime and nighttime series (P less than 0.05 for nighttime HOI). Cardiac output increased from 3.3 1/min before HOI to 5–6 1/min during HOI without showing any significant circadian difference. Hematocrit, hemoglobin, and plasma concentrations remained unchanged under all conditions. It is concluded that the renal response to HOI is subject to nocturnal inhibition, which cannot be attributed to circadian differences in the degree of HOI-induced central blood pooling, renin-aldosterone, or ADH responses.

Analgesic Effects of Different Acupoint Stimulation Frequencies in Humans

2003 ◽  
Vol 31 (01) ◽  
pp. 157-162 ◽  
Author(s):  
Anoja S. Attele ◽  
Sangeeta Mehendale ◽  
Xiongfei Guan ◽  
Lucy Dey ◽  
Chun-Su Yuan
Keyword(s):  
Pain Score ◽  
Pain Treatment ◽  
Human Subjects ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Controlled Study ◽  
Healthy Human ◽  
Pressor Test ◽  
Significant Difference ◽  
Acupoint Stimulation

Transcutaneous electrical acupoint stimulation (TEAS) provides a convenient and standardized technique for pain treatment. The cold-pressor test is a simple and reliable model in humans for the induction of tonic pain. In this controlled study, the effects of TEAS on cold pressor-induced pain were evaluated in 22 healthy human subjects. Electrical stimulation at 4 Hz and 32 Hz was applied to He-Gu (LI 4) and Nui-Guan (P 6) acupoints for 15 minutes. Pain score ratings were evaluated at four time points from 30–170 seconds during the cold-pressor test. We observed an analgesic effect at both 4 Hz and 32 Hz of stimulation, and pain score rating reductions were statistically significant compared to control (p < 0.01). Our data support the efficacy of TEAS analgesia. However, there was no significant difference between pain scores at 4 Hz and 32 Hz stimulation.

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