Transhepatic absorption and biliary excretion of insulin

1987 ◽  
Vol 65 (9) ◽  
pp. 1982-1987 ◽  
Author(s):  
Walter Zingg ◽  
Aron M. Rappaport ◽  
Bernard S. Leibel
Keyword(s):  
Intravenous Administration ◽  
Biliary Excretion ◽  
Venous Blood ◽  
Intraperitoneal Administration ◽  
Liver Cells ◽  
Insulin Concentration ◽  
Secretory Process ◽  
Insulin Administration ◽  
Hepatic Cells ◽  
Liver Surface

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.

scholarly journals Pharmacokinetics of Intermittent Intravenous Cefazolin and Tobramycin in Patients Treated with Automated Peritoneal Dialysis

2000 ◽  
Vol 11 (7) ◽  
pp. 1310-1316
Author(s):  
HAROLD J. MANLEY ◽  
GEORGE R. BAILIE ◽  
REGINALD FRYE ◽  
LORRAINE D. HESS ◽  
M. DONALD MCGOLDRICK
Keyword(s):  
Peritoneal Dialysis ◽  
Intravenous Administration ◽  
Intraperitoneal Administration ◽  
Intravenous Dose ◽  
Urine Samples ◽  
Pharmacokinetic Parameters ◽  
Single Intravenous Dose ◽  
Automated Peritoneal Dialysis ◽  
Minimum Inhibitory Concentrations ◽  
Monoexponential Model

Abstract. There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler : 10.67 ± 4.66 h ; cefazolin off cycler : 23.09 ± 5.6 h ; P = 0.001 ; tobramycin on cycler : 14.27 ± 4.53 h ; tobramycin off cycler : 68.5 ± 26.47 h ; P < 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg) ; however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients.

scholarly journals Intercellular Communication between Hepatic Cells in Liver Diseases

2019 ◽  
Vol 20 (9) ◽  
pp. 2180 ◽  
Author(s):  
Keisaku Sato ◽  
Lindsey Kennedy ◽  
Suthat Liangpunsakul ◽  
Praveen Kusumanchi ◽  
Zhihong Yang ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Therapeutic Target ◽  
Liver Diseases ◽  
Cell Communication ◽  
Liver Cells ◽  
Small Particles ◽  
Hepatic Cells ◽  
Donor Cells ◽  
Parenchymal Cells ◽  
Novel Therapeutic

Liver diseases are perpetuated by the orchestration of hepatocytes and other hepatic non-parenchymal cells. These cells communicate and regulate with each other by secreting mediators such as peptides, hormones, and cytokines. Extracellular vesicles (EVs), small particles secreted from cells, contain proteins, DNAs, and RNAs as cargos. EVs have attracted recent research interests since they can communicate information from donor cells to recipient cells thereby regulating physiological events via delivering of specific cargo mediators. Previous studies have demonstrated that liver cells secrete elevated numbers of EVs during diseased conditions, and those EVs are internalized into other liver cells inducing disease-related reactions such as inflammation, angiogenesis, and fibrogenesis. Reactions in recipient cells are caused by proteins and RNAs carried in disease-derived EVs. This review summarizes cell-to-cell communication especially via EVs in the pathogenesis of liver diseases and their potential as a novel therapeutic target.

Differences in specific activity of calcium in blood and urine of dogs

1964 ◽  
Vol 206 (4) ◽  
pp. 755-761 ◽  
Author(s):  
E. J. Miller ◽  
W. F. Neuman ◽  
P. M. Bazerque
Keyword(s):  
Intravenous Administration ◽  
Specific Activity ◽  
Intraperitoneal Administration ◽  
Kidney Tissue ◽  
Early Time ◽  
Calcium Excretion ◽  
Urine Calcium ◽  
Activity Ratios ◽  
Tissue Calcium ◽  
Stable Calcium

Following intravenous administration of radioactive calcium, no differences were observed between blood and urine calcium specific activities even at early time periods. Following intraperitoneal administration of similar isotope solutions, however, a considerable discrepancy was noted between the specific activity in the two compartments, the urine specific activity remaining lower than that of the blood for as long as 5 hr. This same phenomenon was apparent after intravenous administration of radioactive calcium if a solution were injected intraperitoneally at the time of isotope administration. Blood/urine specific activity ratios exceeding unity were associated with periods of low calcium excretion. Adrenergic drugs, injected intravenously, were found to mimic intraperitoneal injections of isotope solutions. The response to intraperitoneal injections could not be blocked by atropine, but was absent in the presence of Dibenamine. It was concluded that an intraperitoneal injection had altered renal hemodynamics through a neural response which appeared to be sympathetically mediated. No evidence was found for a nonhomogeneous distribution of exogenous labeled calcium among the plasma calcium fractions. It is suggested that kidney tissue calcium is the source of the disproportionate amount of stable calcium appearing in the urine.

SECRETION OF TESTOSTERONE BY THE EUTOPIC AND THE CRYPTORCHID TESTES IN THE SAME DOG

1966 ◽  
Vol 44 (4) ◽  
pp. 629-633 ◽  
Author(s):  
Kristen B. Eik-Nes
Keyword(s):  
Intravenous Administration ◽  
Venous Blood ◽  
Cryptorchid Testis ◽  
Secretion Rates

The concentration of testosterone has been measured in spermatic venous blood from eutopic and cryptorchid testes in the same anesthetized dog in experiments lasting for 90 minutes. Both testes secreted testosterone and increased production of the hormone following intravenous administration of gonadotrophin. The production of testosterone by the cryptorchid testis was, however, lower than that by the eutopic organ thus demonstrating that the condition of cryptorchism is associated with decreased secretion rates of testosterone in the canine.

scholarly journals Intraperitoneal administration of mesenchymal stem cells is effective at mitigating detrusor deterioration after pBOO

2020 ◽  
Vol 318 (3) ◽  
pp. F549-F556 ◽  
Author(s):  
Bridget Wiafe ◽  
Rutuja Kadam ◽  
Peter D. Metcalfe
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intravenous Administration ◽  
Transforming Growth Factor ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Intraperitoneal Administration ◽  
Outlet Obstruction ◽  
Systemic Exposure ◽  
Transforming Growth Factor Β

Partial bladder outlet obstruction (pBOO) results in bladder fibrosis that is initiated by an inflammatory cascade and the decompensation after smooth muscle hypertrophy. We have been using an animal model to develop the hypothesis that mesenchymal stem cells (MSCs) are able to mitigate this cytokine cascade and prevent bladder deterioration. We hypothesized that intraperitoneal administration of MSCs can produce the same effects as intravenously administered cells but may require higher dosing. Intraperitoneal treatment will provide insights into the mechanisms of action and may offer advantages over intravenous administration, as it will permit allow higher doses and potentially reduce systemic exposure. Rats underwent a surgical induction of pBOO and instillation of either 1 × 106 or 5 × 106 commercially acquired MSCs into the peritoneum. RT-PCR, immunohistochemistry, and urodynamics were used to compare treatment groups with controls. pBOO resulted in a marked, statistically significant, upregulation of inflammatory markers in the bladder, including transforming growth factor-β, hypoxia-inducible factor-1α, hypoxia-inducible factor-3α, mammalian target of rapamycin, and collagen types I and III. Moderate but inconsistent levels of downregulation were seen with 1 × 106 MSCs, but excellent and reliable downregulation was seen with 5 × 106 MSCs ( P < 0.05). Immunohistochemistry confirmed that protein levels were affected in accordance with mRNA upregulation. Urodynamics demonstrated MSC treatment resulted in whole organ physiological benefits, as they prevented elevations in detrusor pressure. In conclusion, intraperitoneal administration of MSCs resulted in a similar effect as intravenous administration; however, this required a higher dose. This has significant implications for determining the mechanism of action and potential clinical application for human therapy.

scholarly journals The Effect of Intravenous Histamine Administration on the Level of the White Blood Count in the Peripheral Blood

Blood ◽  
1951 ◽  
Vol 6 (10) ◽  
pp. 926-935 ◽  
Author(s):  
HOWARD R. BIERMAN ◽  
KEITH H. KELLY ◽  
NICHOLAS L. PETRAKIS ◽  
FAUNO CORDES ◽  
MARILEE FOSTER ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Peripheral Blood ◽  
Pulmonary Circulation ◽  
White Cell Count ◽  
Venous Blood ◽  
Peripheral Circulation ◽  
White Blood Count ◽  
Clotting Time ◽  
Arterial Blood ◽  
Leukocyte Number

Abstract 1. By simultaneously sampling venous and arterial blood by cardiac catheterization or vessel cannulation, the number of leukocytes entering and leaving the lungs was observed in 12 patients on 14 occasions. 2. The intravenous administration of histamine phosphate in doses of 0.1 to 0.3 mg. (as base) over 10 to 60 seconds, was accompanied by a prompt decrease in leukocyte number in the arterial blood 20 to 60 seconds before the venous white cell count fell. This was interpreted as demonstrating that the leukocytes were removed from tine peripheral blood in the pulmonary circulation. The granulocytic series appeared to be more involved in the leukopenia, although a similar but less apparent change was noted in the agranulocytes. 3. The leukopenia persisted for 40 to 180 seconds following which the arterial leukocyte count exceeded that in the venous blood indicating a return of leukocytes from the lungs into the peripheral circulation. 4. The intravenous administration of histamine also resulted in an immediate decrease in clotting time as determined both by glass and siliconed tube technics. 5. The intravenous injection of histamine affords a relatively simple technic to study one type of leukocyte removal mechanism present in the pulmonary circulation.

scholarly journals Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Chi Liu ◽  
Ryosuke Kurokawa ◽  
Masayuki Fujino ◽  
Shinichi Hirano ◽  
Bunpei Sato ◽  
...  
Keyword(s):  
Hydrogen Concentration ◽  
Intravenous Administration ◽  
Molecular Hydrogen ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intraperitoneal Administration ◽  
Hydrogen Gas ◽  
Rat Blood ◽  
Beneficial Effects ◽  
Rat Tissue

Abstract Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS) and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen.

scholarly journals Biliary excretion of [14C]succinylsulphathiazole in the rat and rabbit

1967 ◽  
Vol 105 (3) ◽  
pp. 1295-1299 ◽  
Author(s):  
M M Abou-el-Makarem ◽  
P Millburn ◽  
R L Smith
Keyword(s):  
Intravenous Injection ◽  
Biliary Excretion ◽  
Concentration Gradient ◽  
Bile Salts ◽  
Liver Cells ◽  
Simultaneous Administration ◽  
The Poor ◽  
Two Factors

1. After intravenous injection about 30% of the dose (20mg./kg.) of succinylsulphathiazole is excreted unchanged in the bile in 3hr. by the rat, whereas only about 1% is excreted by the rabbit. When the renal pedicles are ligated the biliary excretion of succinylsulphathiazole in the rat increases to about 80% of the dose, but in the rabbit under these conditions the biliary excretion is only 2% of the dose. 2. In the rat, the sulphonamide readily enters the liver and biliary excretion occurs against a concentration gradient from liver to bile; further, the excretory process can be saturated, and can be depressed by the simultaneous administration of phenolphthalein glucuronide or bile salts. 3. In the rabbit, these conditions have not been found; succinylsulphathiazole does not readily enter the liver from the plasma, there is no transfer of the drug from the liver cells to the bile against a concentration gradient, and no saturation or depression of the biliary excretion of succinylsulphathiazole is found. 4. It is suggested that two factors responsible, at least partly, for the low biliary excretion of succinylsulphathiazole in the rabbit are the poor entry of the sulphonamide into the liver in this species and a deficiency of the concentrative mechanism for its excretion in the bile.

Biliary excretion of radioactivity after intravenous administration of [3H]25-hydroxyvitamin D3 in man

1986 ◽  
Vol 31 (4) ◽  
pp. 361-368 ◽  
Author(s):  
Julia E. Ledger ◽  
Graham J. Watson ◽  
Juliet E. Compston
Keyword(s):  
Intravenous Administration ◽  
Biliary Excretion
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