Metabolic alkalosis in models of primary and secondary hyperparathyroid states

1983 ◽  
Vol 245 (4) ◽  
pp. F450-F461 ◽  
Author(s):  
H. N. Hulter ◽  
R. D. Toto ◽  
L. P. Ilnicki ◽  
B. Halloran ◽  
A. Sebastian
Keyword(s):  
Steady State ◽  
Intravenous Infusion ◽  
Metabolic Alkalosis ◽  
Extracellular Fluid ◽  
Chronic Administration ◽  
Systemic Circulation ◽  
Acute Administration ◽  
Group Iii ◽  
Group I ◽  
Renal Origin

Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional adaptation to reduced renal mass in early development

1982 ◽  
Vol 242 (2) ◽  
pp. F190-F196 ◽  
Author(s):  
R. L. Chevalier
Keyword(s):  
Renal Mass ◽  
Left Kidney ◽  
Extracellular Fluid ◽  
Functional Adaptation ◽  
Fluid Loss ◽  
Group Iii ◽  
Arterial Blood ◽  
India Ink ◽  
Group I ◽  
Group Ii

To determine whether reduced renal mass in the newborn results in acceleration of normal renal development, the response to unilateral nephrectomy (N) before 36 h of age was compared with sham-operated (S) guinea pigs during the period of most rapid nephron maturation. Studies were performed at 7-13 days (group I) and 19-25 days (group II). Mean arterial blood pressure (AP), left kidney glomerular filtration rate (LKGFR), and urine sodium excretion (UNaV) were measured. Superficial single nephron GFR (sSNGFR) and proximal fractional water reabsorption (FRH2O) were measured by micropuncture, and the number of glomeruli (NG) was determined by India ink perfusion. In view of the susceptibility of the neonate to extracellular fluid loss, groups I and II were plasma infused to maintain euvolemia and group II was compared with 19- to 25-day-old hydropenic animals (group III). Increase in body weight with age was unaffected by neonatal N. In group IN, the compensatory increase in sSNGFR was greater than SNGFR for deeper nephrons, which normally contribute most to GFR at this age. In group IIN there was an 80% adaptive increase in LKGFR that could not be entirely explained by the rise in SNGFR. Since NG in group IIN was greater than in group IIS and similar to that in adulthood, the enhanced adaptation in LKGFR in group IIN may be due in part to earlier recruitment of a population of underperfused glomeruli. FRH2O did not change significantly with age and did not differ in N and S groups. Animals in group III developed a rise in hematocrit during the experiment, and AP, LKGFR, and UNaV were lower in group IIIN than in group IIN. It is concluded that following N at birth, the sequence of renal functional maturation is accelerated while glomerulotubular balance is preserved. As a result of these adaptative changes, homeostasis is maintained and body growth proceeds without impairment.

Distribution of H+ and HCO3 minus between CSF and blood during metabolic alkalosis in dogs

1975 ◽  
Vol 228 (4) ◽  
pp. 1141-1144 ◽  
Author(s):  
EG Pavlin ◽  
ttf Hornbein
Keyword(s):  
Cerebrospinal Fluid ◽  
Steady State ◽  
Metabolic Alkalosis ◽  
Extracellular Fluid ◽  
Ion Distribution ◽  
Brain Extracellular Fluid ◽  
Dc Potential ◽  
Arterial Plasma ◽  
Lumbar Cerebrospinal Fluid

In anesthetized, paralyzed dogs ventilated to maintain a normal PaCO2, metabolic alkalosis was induced and held constant over 6 h by infusion of sodium bicarbonate. Determination of pH, PCO2, (HCO3 minus), and (lactate) in cisternal and lumbar cerebrospinal fluid (CSF) and in arterial plasma together with measurement of the CSF/plasma DC potential differences permitted calculation of the electrochemical potential difference (mu) for H+ and HCO3 minus; measurements were made prior to induction of metabolic alkalosis at pHa equal to 7.40, as soon after induction as stable arterial values were achieved and 3, 4.5, and 6 h thereafter. A steady state for ion distribution was reached by 4.5 h. Values of mu for H+ and HCO3 minus returned to +0.1 and +0.9 mV of control at 6 h for cisternal CSF and +0.6 and minus 0.4 mV for lumbar CSF. This return of muH+ and muHCO3 minus close to control in the steady state is compatible with passive distribution of these ions between brain extracellular fluid and blood.

scholarly journals Influence of chronic administration of zearalenone on the processes of apoptosis in the porcine ovary

2012 ◽  
Vol 50 (No. 12) ◽  
pp. 531-536 ◽  
Author(s):  
K. Wasowicz ◽  
M. Gajecka ◽  
J. Calka ◽  
E. Jakimiuk ◽  
M. Gajecki
Keyword(s):  
Body Weight ◽  
Estrogen Receptors ◽  
Chronic Administration ◽  
Nuclear Antigen ◽  
Endocrine Regulation ◽  
Proliferating Cells ◽  
Inhibition Of Proliferation ◽  
Group Iii ◽  
Group I ◽  
Fusarium Sp

Zearalenone (ZEA), a micotoxin produced by Fusarium sp. is regarded as a phytoestrogen. Although cytotoxic and genotoxic activity of ZEA was detected, the majority of its toxic influence is related to the ability of binding to estrogen receptors and disrupting the endocrine regulation of the reproductory functions in females. It was previously found that ZEA inhibits proliferation of cells in porcine ovaries, as detected with immunostaining for proliferating cells nuclear antigen (PCNA). The number of PCNA-positive cells was inversely proportional to the dose of ZEA. We decided to answer the question of whether ZEA induces apoptosis in porcine ovaries. Experimental gilts (before first estrus) were fed ZEA in a dosage of 20 (group II) or 40 (group III) µg/kg of body weight/day for 63 days. Control animals (group I) were fed a placebo. After that period animals were sacrificed, ovaries were extirpated, fixed in paraformaldehyde solution, cut into sections with a cryostat and studied for apoptosis with TUNEL kit, and for the presence of apoptosis-promoting protein Bax with immunohistochemistry. It was found that apoptosis was detected with TUNEL only in medium-sized antral ovarian follicles in animals of groups I and II. No apoptosis signal was found in the ovaries of animals in group III. No differences in the distribution and intensity of staining for Bax were found between animals of all investigated groups. The results indicate that ZEA do not induce apoptosis in porcine ovaries, and the inhibition of proliferation must be associated with other mechanisms.

Spectrum of orthostatic disorders: Classification based on an analysis of the short-term circulatory response upon standing

1991 ◽  
Vol 81 (2) ◽  
pp. 241-248 ◽  
Author(s):  
W. Wieling ◽  
A. D. J. ten Harkel ◽  
J. J. van Lieshout
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Steady State ◽  
Maximum Heart Rate ◽  
Circulatory Response ◽  
Group Iii ◽  
Additional Information ◽  
Postural Tachycardia ◽  
Group I ◽  
Circulatory Control

1. In 31 consecutively referred patients (20 females, 11 males) with overt or suspected orthostatic disorders, the changes in blood pressure and heart rate that occur in the first 2 min of standing were analysed. 2. Blood pressure was measured continuously by Finapres. The blood pressure and heart rate responses after 1–2 min of standing (early steady-state response) were used to classify the patients as follows: group I (n = 17, age 42 ± 17 years), normal early steady-state blood pressure and heart rate responses; group II (n = 5, age 40 ± 14 years), combination of normal early steady-state blood pressure and postural tachycardia; group III (n = 9, age 51 ± 14 years), hypotensive orthostatic response with (4/9) or without (5/9) postural tachycardia. We examined whether additional information could be obtained by beat-to-beat analysis of the initial circulatory response (first 30 s). It was quantified by identifying the blood pressure trough and overshoot and the maximum heart rate and relative bradycardia. 3. The initial drop in systolic and diastolic blood pressures did not differ between the three groups. A recovery of blood pressure with a systolic and/or diastolic blood pressure overshoot was present in all group I and II patients, but was absent in all except two patients in group III. The initial maximum heart rate increase did not differ between the three groups. The relative bradycardia was less in groups II and III than in group I. 4. We conclude that analysis of the beat-to-beat blood pressure changes in the first 30 s after the onset of standing provides almost all the information that is necessary to determine abnormalities in orthostatic circulatory control.

Effects of glucocorticoid steroids on renal and systemic acid-base metabolism

1980 ◽  
Vol 239 (1) ◽  
pp. F30-F43 ◽  
Author(s):  
H. N. Hulter ◽  
J. H. Licht ◽  
E. L. Bonner ◽  
R. D. Glynn ◽  
A. Sebastian
Keyword(s):  
Steady State ◽  
Acid Production ◽  
Chronic Administration ◽  
Acid Excretion ◽  
Acid Base ◽  
Unmeasured Anion ◽  
Urine Ph ◽  
Group I ◽  
Potassium Clearance ◽  
Net Acid Excretion

Clinical states of hyperglucocorticoidism are associated with renal metabolic alkalosis, yet the systemic and renal acid-base response to chronic administration of glucocorticoid steroids (dexamethasone, triamcinolone) possessing little or no mineralocorticoid activity has not been investigated. In balance studies studies in dogs administration of triamcinolone (Tcn), 1.0 mg. kg-1. day-1 for 6–9 days (group I, n = 5), resulted in a persistent reduction in urine pH and increase in net acid excretion (NAE), and in the excretion of urinary unmeasured anions (C+NH4,Na;K minus A-Cl,HCO3,Pi), which were identified as organic anions and sulfate. A significant degree of metabolic acidosis occurred initially (delta [HCO3-]p, -3.4 meq/liter, P less than 0.05, day 1). As Tcn administration was continued, the cumulative increment in net acid excreted exceeded the cumulative increment in urinary unmeasured anion excreted and [HCO-3]p returned to pre-Tcn control values and remained stable thereafter. In the steady state of Tcn administration plasma potassium concentration and renal potassium clearance were not significantly different from pre-Tcn control, in contrast to the findings of hypokalemia and increased renal potassium clearance during chronic administration of deoxycorticosterone (DOC). Triamcinolone did not result in antinatriuresis or antichloruresis. Chronic administration of a 10–fold smaller dose of Tcn (0.1 mg . kg-1 . day-1) in an additional group (group III) also resulted in a persisting reduction in urine pH and an increase in net acid excretion that exceeded unmeasured anion excretion and resulted in a small increase in steady-state plasma bicarbonate concentration. These results suggest that chronic administration of potent glucocorticoid steroids results in 1) a persisting increase in endogenous acid production, and 2) stimulation of renal hydrogen ion secretion that was of greater degree than accounted for by the increment in endogenous acid production and that was not accompanied by renal mineralocorticoid effects on sodium and potassium transport.

scholarly journals The Hepatoprotector Effect of Uncaria gambir Roxb Extract in Wistar Rats Induced by Paracetamol

2020 ◽  
Vol 10 (6-s) ◽  
pp. 61-66
Author(s):  
, Suparni ◽  
, Musthari ◽  
Liza Mutia ◽  
Mangoloi Sinurat ◽  
Siti Syarifah ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Chronic Administration ◽  
Liver Cells ◽  
Group Iv ◽  
Drug Induced ◽  
Significant Differentiation ◽  
Group Iii ◽  
Hepatoprotector Activity ◽  
Group I ◽  
Group Ii

Background: Drug induced liver injury (DILI) is known as the damage of liver cells due to chronic administrations of drug. The chronic administration of paracetamol could be trigger the damage of liver cells.The hepatoprotector agents are still limited worldwide.  Gambier(Uncaria gambir Roxb) is an Indonesia’traditional medicine which have many benefits as antioxidant, antiseptic, antidiarrhoea, etc  that commonly used in society.  Method: The present study was conducted to investigate the hepatoprotector effect ofgambier in wistar rats induced by paracetamol.  The wistar rats were divided into seven groups and received the treatment orally for 12 days. Group I (aquadest), II(curcuma,400 mg/kgBW),III (gambier,26 mg/200gr), IV(gambier, 53 mg/200gr), V(gambier,106 mg/200gr),VI(gambier,212 mg/200gr) and VII(gambier,424mg/200gr). Termination, blood and liver organ collection were done after all group induced by paracetamol for two days. Histopatology changes of liver were examined using Hematoxycilline (HE) staining. AST and ALT levels were analyzed. Results: There were significant differentiation of AST levels among the groups, especially between group I and group IV and between group II and group IV. The ALT levels were statistically significant between group II and group V using Mann-Whitney test (p<0,05). In histopatology examination, there were significant differentiation between group I with another group, not only group II but also group III-VII (p<0,05). In the treatment group, group III and IV had been showed the improvement of liver cells damage than group I by using One-way Annova, post hoc Bonferroni (p<0,05). Conclusion: Uncaria gambir Roxb has hepatoprotector activity start at dose 53 mg/200grBWin rats.  The hepatoprotector activity was not superior than curcuma.  Keywords: hepatoprotector, Uncaria gambir Roxb, AST,ALT,histopatology

Juxtamedullary nephrons during acute metabolic alkalosis in the rat

1985 ◽  
Vol 249 (1) ◽  
pp. F107-F116
Author(s):  
J. P. Frommer ◽  
D. E. Wesson ◽  
M. E. Laski ◽  
N. A. Kurtzman
Keyword(s):  
Metabolic Alkalosis ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Group Iv ◽  
Renal Handling ◽  
Group Iii ◽  
Contralateral Kidney ◽  
Group I ◽  
Papillary Collecting Duct

The renal handling of bicarbonate during acute metabolic alkalosis was examined in Munich-Wistar rats using micropuncture techniques. Group I received an acute bicarbonate load, and fractional delivery of total CO2 (tCO2) (FDtCO2) to the superficial late distal tubule (LD) was significantly lower than to the base of the papillary collecting duct (B) (18.4 +/- 1.7 vs. 22.9 +/- 1.5%; P less than 0.01), indicating net addition of bicarbonate between LD and B. When acutely bicarbonate-loaded rats had their deep nephrons destroyed with bromoethylamine hydrobromide (BEA) (group II), net addition of tCO2 between LD and B was abolished and net reabsorption uncovered (FDtCO2 LD: 28.0 +/- 3.6 vs. B: 17.5 +/- 2.5%; P less than 0.01). The infusion of amiloride (2.5 mg/kg body wt) to alkalotic rats treated with BEA (group III) completely inhibited distal bicarbonate reabsorption but did not reestablish addition (FDtCO2 LD: 27.6 +/- 1.6 vs. B: 26.1 +/- 3.7%; P = NS). The values obtained for sham-operated animals (group IV) were the same for group I. The patterns that were observed between LD and B were reproduced for the four groups of animals when FDtCO2 LD was compared with the fractional excretion of bicarbonate in the urine of the intact contralateral kidney. These studies suggest that juxtamedullary nephrons contribute a higher load of bicarbonate than superficial nephrons to the final urine during acute metabolic alkalosis in the rat.

Effects on tissue and electrolytes of a mineralocorticoid blocker during DOCA-induced potassium depletion

1976 ◽  
Vol 54 (1) ◽  
pp. 59-65 ◽  
Author(s):  
David Z. Levine ◽  
Kiriti Sarkar
Keyword(s):  
Metabolic Alkalosis ◽  
Myocardial Necrosis ◽  
Blocking Agent ◽  
Dose Ratio ◽  
Group Iii ◽  
Group I ◽  
Daily Dose ◽  
Histological Abnormality ◽  
Group Ii ◽  
Electrolyte Effects

Chronic experiments were carried out on three groups of rats to evaluate tissue and electrolyte effects of a mineralocorticoid blocker canrenoate potassium (SC-14266) during DOCA-induced hypokalemic metabolic alkalosis. Group I animals received DOCA alone, group II received DOCA plus canrenoate, while group III received canrenoate alone. The daily dose ratio (per kilogram of body weight) was 180 mg canrenoate – 0.45 mg DOCA. All animals ate a synthetic diet and drank 0.15 N NaHCO3 Group II animals demonstrated a lesser degree of metabolic alkalosis and a higher muscle potassium content when compared with group I rats. The most conspicuous histological abnormality was myocardial necrosis, the degree and extent of which was impressively reduced by the blocking agent.

scholarly journals Pharmacokinetics and Safety of Oral Posaconazole in Neutropenic Stem Cell Transplant Recipients

2006 ◽  
Vol 50 (6) ◽  
pp. 1993-1999 ◽  
Author(s):  
Paul O. Gubbins ◽  
Gopal Krishna ◽  
Angela Sansone-Parsons ◽  
Scott R. Penzak ◽  
Li Dong ◽  
...  
Keyword(s):  
Stem Cell ◽  
Steady State ◽  
Maximum Plasma ◽  
Cell Transplant ◽  
Once Daily ◽  
Daily Group ◽  
Group Iii ◽  
Group I ◽  
Dosing Frequency ◽  
Group Ii

ABSTRACT The pharmacokinetics of posaconazole oral suspension in neutropenic patients undergoing high-dose chemotherapy and stem cell transplantation were evaluated, and the association of plasma posaconazole exposure with the presence and severity of oral mucositis was explored in this nonrandomized, open-label, parallel-group, multiple-dose pharmacokinetic study. Thirty patients were enrolled and received one of three regimens (group I, 200 mg once daily; group II, 400 mg once daily; group III, 200 mg four times daily) for the duration of neutropenia. The mean total exposure for day 1, as shown by the area under the concentration-time curve from 0 to 24 h (AUC0-24), was 1.96 mg · h/liter in group I and was 51% higher in group II and in group III. Increases in AUC0-24 and maximum plasma concentration (C max) in groups II and III were dose related. The AUC0-24 and C max values on day 1 were similar between groups II and III. There was interpatient variability of up to 68% in the pharmacokinetic values for our study population. Steady state was attained by days 5 to 6. Average steady-state plasma posaconazole trough values were 192, 219, and 414 ng/ml in groups I, II, and III, respectively. The AUC0-24 and apparent oral clearance increased by increasing dose and dosing frequency. Mucositis appeared to reduce exposure but did not significantly affect mean total posaconazole exposure (AUC and C max) at steady state (P = 0.1483). Moreover, this reduction could be overcome by increasing the total dose and dosing frequency. Posaconazole was safe and well tolerated.

Changes in brain ECF pH during metabolic acidosis and alkalosis: a microelectrode study

1983 ◽  
Vol 55 (6) ◽  
pp. 1849-1853 ◽  
Author(s):  
S. Javaheri ◽  
A. De Hemptinne ◽  
B. Vanheel ◽  
I. Leusen
Keyword(s):  
Cerebrospinal Fluid ◽  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Extracellular Fluid ◽  
Acid Base ◽  
Brain Extracellular Fluid ◽  
Group I ◽  
Venous Pco2 ◽  
Anesthetized Dogs ◽  
Acute Metabolic Acidosis

We used pH-sensitive double-barreled microelectrodes to measure brain extracellular fluid (ECF) pH in anesthetized dogs during isocapnic infusion acidosis (HCl) and alkalosis (Na2CO3) of 45-60 min duration. The diameter of the tips of these electrodes varied from less than 1 to 27 micron and were placed 5 mm below the surface of the parietal cortex. In group I (metabolic acidosis, n = 5) mean plasma and brain ECF pH fell significantly by 0.221 and 0.025, respectively, with changes in brain ECF pH being 11.3% of those noted in plasma. In group II (metabolic alkalosis, n = 5) mean plasma and brain ECF pH rose significantly by 0.170 and 0.049, respectively, with changes in brain ECF pH being 28.8% of those noted in plasma. Mean arterial and sagittal venous PCO2 and cisternal cerebrospinal fluid (CSF) acid-base variables did not change significantly during acid or base infusion. We conclude that during transients of isocapnic metabolic acid-base perturbations ionic gradients exist between brain ECF and CSF and that changes in brain ECF pH measured by microelectrodes follow the changes in plasma pH. These pH changes may play an important role in respiratory adaptations of acute metabolic acidosis and alkalosis.

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