BACKGROUND: Previous studies into the relevance of a putative circulating factor in the pathogenesis of minimal change nephrotic syndrome have opened the possibility that plasma hemopexin might be an important effector molecule in this disorder. Thus, intra renal infusion of isolated plasma hemopexin into rats induced minimal change like glomerular ...

It is well known that IAP elevation, even at the level of 10mmHg used for laparoscopic surgery leads to an increase in portal pressure and decrease in portal blood flow. Since hepatic hemodynamics are already disturbed in cirrhotics, we decided to investigate the possible role of chronically elevated intra-abdominal pressure ...

Experimental approaches involving the perfusion of tissues and organs offer the advantage of improved physiological relevance over the use of isolated tissues or cells while at the same time being much more controlled and tissue-specific than studies in vivo. Nevertheless, there have been few metabolic studies performed in perfused white ...

This paper reviews different investigations carried out with Long-Evans rats on the influence of age on the ototoxicity induced by styrene and on the vulnerability to noise. The first part of this article is focused on the differences in auditory susceptibility to noise (92 or 97dB octave band noise centered ...

OBJECTIVE: During biliary cirrhosis in rats, organic anion-transporting peptides (Oatps) and ATP-dependent multidrug resistance-associated protein 2 (Mrp2) that are likely to transport the contrast agent Gd-BOPTA through hepatocytes are down-regulated. However, the consequences of such down-regulation on the signal intensity (SI) enhancement are unknown. Consequently, the aim of our study ...

Liver fibrosis is characterized by abnormal accumulation of extracellular matrix (ECM), namely, fibrillar collagens in the hepatic stellate cells (HSCs). Earlier, we developed an antigene approach, using a type alpha1(I) collagen gene promoter specific triplex-forming oligonucleotide (TFO) to inhibit collagen gene expression. In this paper, to enhance overall delivery of ...

We previously reported that a lethal dose of monochloroacetate (MCA) causes severe hypoglycemia and lactic acidosis. MCA has been thought to inhibit mitochondrial aconitase; however, the exact effect of MCA on hepatic glucose metabolism is not clear. In this study, we investigated the effects of MCA on liver gluconeogenesis using ...

For more than 40 years coumarin has been successfully used in the therapy of chronic venous insufficiency (CVI). The occurrence of liver injuries is rather rare and happens predominantly when doses are administered which are significantly higher than necessary for therapeutical use. Such effects caused by high coumarin concentrations are ...

The isolated perfused rat liver (IPRL) has been extensively used as an intact organ model for determination of hepatic clearance and metabolism of drugs. The IPRL model can also be applied to determine physiologically based pharmacokinetics. Since the IPRL model avoids neural and hormonal interferences and excludes influences from absorption ...

The electroneutral, Na(+)-coupled HCO(3)(-) co-transporter (NBCn1) is expressed in the basolateral membrane of rat medullary thick ascending limb (mTAL) segments and is up-regulated strongly during metabolic acidosis. We have suggested previously that NBCn1-mediated HCO(3)(-) uptake across the basolateral cell membrane is an important buffering mechanism during the transcellular transport of ...

Using immunofluorescence and 3-dimensional confocal microscopy techniques, the present study was designed to verify if NHE-1 is present at the level of the nuclear membrane in cells that are known to express this type of exchanger. Nuclei were isolated from aortic tissues of adult human, rabbit, and rats, as well ...

BACKGROUND: The effect of the increasing thickness of the glomerular basement membrane (GBM), which is seen in ageing rats, on the effective hydraulic conductivity (k) of the glomerular capillary wall was studied in Wistar rats aged 2 and 18 months. METHODS: With the use of micropuncture techniques, ultrafiltration characteristics of ...

AIM: To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs). METHODS: HSCs isolated from the livers of adult Sprague-Dawley rats (weighing 400-500 g) by in situ perfusion and purified by single-step density gradient centrifugation with Nycodenz, became activated after 10 days' cultivation. ...

AIM: To clarify the protective effect of exogenous adenosine triphosphate (ATP) on hypothermically preserved rat livers. METHODS: Establishment of continuous hypothermic machine perfusion model, detection of nucleotides in hepatocytes with HPLC, measurement of activities of LDH and AST in the perfusate, observation of histopathological changes in different experiment groups, and ...

INTRODUCTION: The rat isolated perfused kidney (IPK) preparation is a very useful model for pharmacokinetic and pharmacologic studies. Bovine serum albumin (BSA) is the oncotic agent used most commonly in IPK models, but the protein is expensive and varies significantly in quality. The present study evaluated the use of dextran ...

The protective effect of Lactobacillus acidophilus and Lactobacillus casei, isolated from fresh cow milk, was studied in vivo. Toxicological data of rat serum revealed that the Lactobacillus isolates had liver improvement functions. Serum alanine aminotransferase (ALT) activities of the rats dosed with Lactobacillus isolates alone were lower (15.50 and 18.27 ...

PURPOSE: To develop an isolated perfused rat liver model to study the hepatic disposition of cyclosporine A (CyA) in both sexes. METHODS: Livers were isolated from male (n = 6) and female (n = 7) rats and perfused with a physiological buffer in a single-pass manner. A bolus 1-mg dose ...

It has been reported that retrograde cerebral perfusion (RCP) provides minimal capillary flow; however, the extent to which RCP can provide aerobic metabolic support is unknown. We evaluated whether perfusate composition optimization for RCP would preserve brain energy metabolism during hypothermic circulatory arrest (HCA) at 20 degrees C in rats. ...

The role of erythrocyte on the hepatic distribution kinetics of antipyrine was investigated in the in situ isolated perfused rat liver. Perfusion experiments were conducted using Krebs-bicarbonate buffer delivered via the portal vein in a single pass mode at a total flow rate of 15 ml/min. A bolus dose of ...

Utilizing push-pull perfusion, we examined secretary profiles of corticotropin-releasing hormone (CRH) in the nucleus paraventricularis (PVN) of freely moving intact (INT) and ovariectomized (OVX) rats, and in the meanwhile the effects of electroacupuncture (EA) on the release patterns of CRH were observed. The PVN was perfused with artificial cerebrospinal fluid ...

1. The metabolism of diallyl disulphide was investigated in vitro with rat and human liver cell subfractions and ex vivo with an isolated perfused rat liver. 2. Diallyl disulphide was oxidized to diallylthiosulphinate by rat liver microsomes with an apparent K(m) = 0.86 +/- 0.1 mM and an apparent V(max) ...

The disposition of digoxin and the influence of the organic anion transporting polypeptide (Oatp)2 inhibitor rifampicin and the P-glycoprotein (P-gp) inhibitor quinidine on its hepatic disposition were examined in the isolated perfused rat liver. Livers from groups of rats were perfused in a recirculatory manner after a bolus dose of ...

This unit describes a method of electrical amygdala kindling in the rat. This procedure requires mastery of stereotaxic electrode implantation which is not covered in the current unit. Also, the investigator must have a sound knowledge of electronics and computing. The text gives instructions on how to render rats epileptic, ...

Foods and complementary medicines contain phytoestrogenic isoflavones such as genistein, which undergo hepatic glucuronidation and excretion into bile and can potentially interfere with the hepatic elimination of other compounds. To investigate this potential, livers from Sprague-Dawley rats were perfused in single-pass mode with preformed gemfibrozil 1-O-acyl glucuronide (GG) (1 microM, ...

Acetylsalicylic acid (ASA) is an antiplatelet agent which has been used in treatment and prevention of stroke in humans. In the present study, the effects of ASA on perfusion deficits in the brain have been studied in an embolic model of stroke. Data showed that perfusion deficits were observed in ...

PURPOSE: To compare in the entire liver, the hepatic kinetics of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine (Gd-DTPA) and to evaluate the hepatic transport of Gd-BOPTA. MATERIALS AND METHODS: The authors studied both contrast agents in isolated perfused rat livers by measuring the magnetic resonance (MR) signal intensity (SI) in ...

This study examines the potential for the phytoestrogenic isoflavones, a type of complementary medicine, to be involved in pharmacokinetic interactions in the liver. Rat livers were isolated and perfused to steady state, in single-pass mode, with either 5 microM paracetamol (n = 6), or 5 microM paracetamol with a 50:50 ...

Metabolic zonation was assessed with the multiple indicator dilution (MID) technique in the single-pass perfused rat liver with use of moment analysis of the formed metabolite (M) data. During single-pass, retrograde rat liver perfusion with 17 Awake M benzoate, a bolus containing tracer preformed metabolite (PM) [(3)H]hippurate was injected rapidly ...

Quercetin has antioxidant, anti-inflammatory, antiproliferative and anticarcinogenic properties. In plant foods, quercetin occurs mainly bound to various sugars via a beta-glycosidic link. We hypothesized that lactase phlorizin hydrolase (LPH), an enzyme at the brush border membrane of intestinal cells, is involved in the in vivo intestinal uptake of quercetin-sugars. To ...

The aim of the present study was to evaluate the potential benefit of machine preservation with the Belzer MPS or HTK solution, compared to standard cold storage, after procurement of marginal livers from non-heart beating donors in an experimental pilot study. Livers from male Wistar rats (250-300 g bw) were ...

1. The metabolism of diallyl disulphide was investigated in vitro with rat and human liver cell subfractions and ex vivo with an isolated perfused rat liver.2. Diallyl disulphide was oxidized to diallylthiosulphinate by rat liver microsomes with an apparent K-m = 0.86 +/- 0.1 mM and an apparent V-max = ...

Vasodilating effects of topically applied lignocaine, papaverine, and chlorpromazine were compared in rats, using a PO2 tissue perfusion monitor and histological analysis. The period of vasospasm was significantly shorter with the use of either 10% lignocaine, 2% papaverine, or 0.25% chlorpromazine than with the use of 2% lignocaine. Although our ...

Kidneys of control and arthritic rats were perfused with a hemoglobin-free perfusion fluid with simultaneous monitoring of perfusion pressure and oxygen uptake. The basal values of renal perfusion pressure were 76.3 +/- 4.63 and 59.96 +/- 3.65 mm Hg in control and arthritic rats, respectively. Infusion of 100 microM Nomega-nitro-L-arginine ...

Uranium is a heavy metal which, following accidental exposure, may potentially be deposited in human tissues and target organs, the kidneys and bones. A few published studies have described the distribution of this element after chronic exposure and one of them has demonstrated an accumulation in the brain. In the ...

Intrahepatic nitric oxide (NO) production is decreased in cirrhotic livers. Our objective was to identify, in cirrhotic rat livers, intrahepatic vascular segments where the deficit of NO facilitates the effect of vasoconstrictors. By using a modified rat liver perfusion system with measurement of both the perfusion and sinusoidal (wedged hepatic ...

OBJECTIVE: The purpose of this study was to investigate and counteract dysfunctional control of capillary flow in hypercholesterolemia. Capillary flow is controlled by arteriolar tone, which in turn is influenced by mediators released from closely paired venules in a mechanism that involves nitric oxide (NO). However, venular control of capillary ...

Asthmatics are known to react to inhaled hyperosmolar solution. Therefore, the effect of hyperosmolar salt solutions on tight junctions of the airway epithelium was investigated by electron microscopy. Rat trachea was perfused with different concentrations of sodium chloride (NaCl) and then fixed from the luminal side with glutaraldehyde to which ...

The permeation characteristics of a model opioid peptide, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE), and its cyclic prodrugs [acyloxyalkoxy-based cyclic prodrug of DADLE (AOA-DADLE), coumarinic acid-based cyclic prodrug of DADLE (CA-DALE), and oxymethyl-modified coumarinic acid-based cyclic prodrug of DADLE (OMCA-DADLE)] across the blood-brain barrier (BBB) were determined using an in situ perfused rat brain ...

Trichloroacetic acid (TCA) is a contaminant of drinking water. It induces peroxisome proliferation in livers of rats and mice and is hepatocarcinogenic in the latter species. Previous experimental studies of the kinetics of TCA in the isolated perfused rat liver (IPRL) at two doses have been reported. To gain more ...

Isolated hepatic perfusion (IHP) with melphalan is used for patients with nonresectable metastases confined to the liver. To improve the efficacy of IHP and to reduce the toxicity to the liver, reversion (retrograde perfusion) of the bloodstream through the liver in a rat model was studied. For liver tumor induction ...

Currently, xenogeneic extracorporeal liver perfusion is used in the treatment of acute liver failure. In order to determine whether transgeneity for human regulatory proteins could improve the functional outcome of the ex-vivo liver in relation to the histopathological changes, we studied the effect of the humoral mechanism in xenogeneic isolated ...

Bromosulfophthalein (BSP) is a relatively nontoxic organic anion used as an in vivo indicator of liver performance. Elimination of BSP via the biliary system following iv injection requires dissociation from albumin in plasma, translocation across the sinusoidal membrane, conjugation with glutathione within the hepatocyte, translocation across the bile canalicular membrane, ...

Modified Hbs are being developed as "blood substitutes," but intravascular injection of diaspirin cross-linked Hb (DBBF-Hb) can produce venular leakage. Hb toxicity may arise from reactive oxygen species, so the antioxidant sodium selenite (Na(2)SeO(3)) was used in an attempt to reduce leak formation. In anesthetized Sprague-Dawley rats, one-half of which ...

A physiologically based pharmacokinetic (PBPK) model for trichloroethylene (TCE) in the male Long-Evans (LE) rat was needed to aid in evaluation of neurotoxicity data collected in this rodent stock. The purpose of this study was to develop such a model with the greatest possible specificity for the LE rat. The ...

BACKGROUND: The benefit of Celsior in liver graft preservation is controversial. In the isolated perfused rat liver model, we compared the effects of Celsior, University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) preservation solutions on liver cell death. METHODS: Rat livers were stored at 4 degrees C for 0, 8, 16, ...

This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides at the hepatic uptake level. Available literature data is provided and new material is presented to picture the differential transport inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in rat liver. ...

Nitroglycerin (NTG), a nitric oxide (NO) donor, has been shown to reduce portal pressure in cirrhotic patients. Using the in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP). Normal and cirrhotic livers were ...

BACKGROUND AND AIM: Hepatic stellate cells (HSC) are located in the space of Disse and are considered to participate in the regulation of sinusoidal flow. The contractility of quiescent HSC in normal liver has remained controversial, unlike activated HSC in injured liver. The aim of the present study was to ...

The aim of this study was to establish whether tooth pulp and periaqueductal central gray (PAG) stimulation affects the release of substance P (SP) into the fluid perfusing the cerebral ventricles in rats. The content of substance P in the cerebrospinal fluid and fluid perfusing cerebral ventricles was determined during ...

Liver hypoxia still represents an important cause of liver injury during shock and liver transplantation. We have investigated the protective effects of beta-alanine against hypoxic injury using isolated perfused rat livers and isolated rat hepatocyte suspensions. Perfusion with hypoxic Krebs-Henseleit buffer increased liver weight and caused a progressive release of ...