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Increased capillary permeability to albumin in diabetic rat myocardium.

To clarify the mechanism for the well-known increase in microvascular permeability that occurs with diabetes mellitus, we investigated capillary permeability to albumin in diabetic rat myocardium by electron microscopy using albumin-gold (Alb-Au) complexes as a tracer. Diabetes was induced by an intravenous injection of streptozotocin. After 24-32 weeks, hearts from diabetic rats and age-matched control rats were perfused with Krebs-Henseleit bicarbonate buffer containing Alb-Au for 5 or 20 minutes and then fixed and processed for electron microscopy. The binding and transport of Alb-Au by capillary endothelium was quantitatively evaluated. In control rats, Alb-Au particles were found preferentially bound to the luminal plasmalemmal vesicles. In diabetic rats, the labeling of luminal vesicles was more extensive and more pronounced after 5 minutes of perfusion when compared with control vesicles. The plasma membrane proper was also heavily labeled in diabetic rats. After 20 minutes, Alb-Au particles were transported across the capillary endothelium via plasmalemmal vesicles, but they did not penetrate the intercellular junctions in either control or diabetic rats. The vesicular transport of Alb-Au across the capillary endothelium was significantly increased in the diabetic myocardium when compared with control myocardium (percentage of abluminal labeled vesicles, 25.9 +/- 5.5% versus 1.3 +/- 0.5%; p < 0.01). The study on food-restricted rats with body weights close to those of diabetic rats suggested that caloric deficiency alone did not have much effect on capillary permeability. The data indicate that capillary permeability to albumin is markedly increased in diabetic myocardium because of enhanced vesicular transport. This may play an important role in the pathogenesis of diabetic cardiomyopathy.

Animals↗

Arachidonic acid metabolites mediate the radiation-induced increase in glomerular albumin permeability.

Radiation-induced renal injury is characterized by proteinuria, hypertension, and progressive decline in renal function. We have previously shown that in vivo or in vitro irradiation of glomeruli with a single dose of radiation (9.5 Gy) increases glomerular albumin permeability (P(alb)) within 1 hr. The current studies tested the hypothesis that this early radiation-induced increase in P(alb) is caused by the release of arachidonic acid and by the generation of specific arachidonic acid metabolites. Glomeruli obtained from WAG/Rij/MCW rats and cultured rat glomerular epithelial and mesangial cells were studied after irradiation (9.5 Gy, single dose). Arachidonic acid release and eicosanoid synthesis by glomeruli or cultured glomerular cells were measured after irradiation, and the effect of inhibitors of phospholipase A2 (PLA2) and cyclooxygenase (COX) on the irradiation-induced increase in P(alb) was assessed. Arachidonic acid release was demonstrated within 10 mins of irradiation of isolated glomeruli and monolayer cultures of glomerular epithelial and mesangial cells. Prostaglandin F(2alpha) (PGF(2alpha)) and PGE2 release was increased after irradiation of isolated glomeruli. Blocking arachidonic acid release or COX activity before irradiation completely prevented the increase in P(alb). COX inhibition immediately after irradiation also diminished the radiation-induced increase in P(alb). We conclude that arachidonic acid and its COX metabolites play an essential role in the early cellular changes that lead to the radiation-induced increase in P(alb). Understanding of the early epigenetic effects of irradiation may lead to new intervention strategies against radiation-induced injury of normal tissues.

Albumins↗

Modification of immune function through exposure to dietary aflatoxin in Gambian children.

Aflatoxins are immunotoxins that frequently contaminate staple foods in The Gambia and other parts of sub-Saharan Africa, resulting in high exposure throughout life. Impaired infant immune system development may be a key predictor of mortality from infectious disease. In this study we aimed to determine the effect of dietary aflatoxin exposure on a number of immune parameters in Gambian children. A cohort of 472 Gambian children 6-9 years of age was recruited. Serum aflatoxin-albumin (AF-alb) adducts were analyzed to provide a measure of exposure. Immune parameters included secretory IgA (sIgA) in saliva, cell-mediated immunity (CMI), determined using the CMI multitest where test antigens are applied to the skin, and antibody responses to both rabies and pneumococcal polysaccharide vaccines. Birth weight, current anthropometry, and micronutrient status were also recorded. AF-alb adducts were detected in 93% of the children (geometric mean level 22.3 pg/mg; range 5-456 pg/mg). AF-alb level was strongly influenced by month of sampling. In a multivariable analysis, sIgA was markedly lower in children with detectable AF-alb compared with those with nondetectable levels [50.4 micro g/mg protein (95% confidence interval [CI] 48.0-52.8) and 70.2 micro g/mg protein (95% CI 61.1-79.2), respectively; p < 0.0001]. Antibody response to one of four pneumococcal serotypes, but not rabies vaccine, was weakly associated with higher levels of AF-alb. There was no association between CMI responses to test antigens and AF-alb. These data confirm that children in rural Gambia are frequently exposed to high levels of aflatoxin. The study provides evidence that sIgA in saliva may be reduced because of dietary levels of aflatoxin exposure. Given the high burden of infection-related mortality in West Africa, further investigation of the immune effects of aflatoxin exposure in children is merited.

Aflatoxins↗

Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa.

Aflatoxins are dietary contaminants that are hepatocarcinogenic and immunotoxic and cause growth retardation in animals, but there is little evidence concerning the latter two parameters in exposed human populations. Aflatoxin exposure of West African children is known to be high, so we conducted a longitudinal study over an 8-month period in Benin to assess the effects of exposure on growth. Two hundred children 16-37 months of age were recruited from four villages, two with high and two with low aflatoxin exposure (50 children per village). Serum aflatoxin-albumin (AF-alb) adducts, anthropometric parameters, information on food consumption, and various demographic data were measured at recruitment (February) and at two subsequent time points (June and October). Plasma levels of vitamin A and zinc were also measured. AF-alb adducts increased markedly between February and October in three of the four villages, with the largest increases in the villages with higher exposures. Children who were fully weaned at recruitment had higher AF-alb than did those still partially breast-fed (p < 0.0001); the major weaning food was a maize-based porridge. There was no association between AF-alb and micronutrient levels, suggesting that aflatoxin exposure was not accompanied by a general nutritional deficiency. There was, however, a strong negative correlation (p < 0.0001) between AF-alb and height increase over the 8-month follow-up after adjustment for age, sex, height at recruitment, socioeconomic status, village, and weaning status; the highest quartile of AF-alb was associated with a mean 1.7 cm reduction in growth over 8 months compared with the lowest quartile. This study emphasizes the association between aflatoxin and stunting, although the underlying mechanisms remain unclear. Aflatoxin exposure during the weaning period may be critical in terms of adverse health effects in West African children, and intervention measures to reduce exposure merit investigation.

Benin↗

Blood-brain barrier permeability of the demented elderly as studied by cerebrospinal fluid-serum albumin ratio.

Blood-brain barrier (BBB) permeability in the demented elderly was investigated by use of the ratio of cerebrospinal fluid (CSF) albumin (Alb) to serum Alb (Q-Alb). Subjects with Alzheimer type dementia (AD), vascular dementia (VD), and controls without dementia (C) were investigated. Patients with AD were divided into mild AD (mAD) and severe AD (sAD) by the use of Hasegawa's dementia scale. The Q-Alb and the ratio of CSF alpha1-antichymotrypsin (ACT) to serum ACT (Q-ACT) were evaluated. Correlations between Q-Alb and Q-ACT were compared among the groups (mAD, sAD, VD, C). Correlations between Q-Alb and major monoaminergic neurochemicals were also analyzed. It was suggested that BBB permeability was preserved in C group, while it was impaired in the patients with VD. In AD group it appeared to be rather well preserved in mAD, while it seemed to be disturbed in a graded manner according to the progression of dementia.

Aged↗

Macular edema reflects generalized vascular hyperpermeability in type 2 diabetic patients with retinopathy.

OBJECTIVE: Diabetic maculopathy (DMa) is the most prevalent sight-threatening type of retinopathy in type 2 diabetes and a leading cause of visual loss in the western world. The disease is characterized by hyperpermeability of retinal blood vessels and subsequent formation of hard exudates and macular edema, the degree of which can be estimated by measurement of retinal thickness. We examined associations between retinal thickness as evaluated by optical coherence tomography scanning (OCT), glomerular leakage as evaluated by urinary albumin excretion rate (UAE), and general vascular leakage as evaluated by the transcapillary escape rate of albumin (TER(alb)) in type 2 diabetic patients with and without DMa. RESEARCH DESIGN AND METHODS: In 20 type 2 diabetic patients with DMa and 20 type 2 diabetic patients without retinopathy matched for age, sex, and duration of diabetes, we performed OCT, fundus photography, fluorescein angiography, and 24-h ambulatory blood pressure measurement. UAE was determined by radioimmunoassay. TER(alb) was determined as the initial disappearance of intravenously injected (125)I-labeled human serum albumin. RESULTS: Patients with diabetic maculopathy had higher HbA(1c) (8.5 +/- 1.5 vs. 7.4 +/- 1.2%, P < 0.05) and higher total cholesterol (5.8 +/- 0.7 vs. 5.2 +/- 0.9 mmol/l, P < 0.05) than patients without retinopathy. UAE was higher in the DMa group than in the group with no retinopathy (9.3 x// 3.1 vs. 3.9 x// 1.9 micro g/min, P < 0.01). There was no difference in TER(alb) between the two groups (6.0 +/- 1.6 vs. 6.6 +/- 1.5%, NS). In the group with DMa, OCT, TER(alb), and UAE correlated significantly (OCT versus TER(alb): r = 0.55, P < 0.05; OCT versus UAE: r = 0.58, P < 0.01; UAE versus TER(alb): r = 0.81, P < 0.01). Conversely, there were no correlations between these three parameters in the group without retinopathy. CONCLUSIONS: Macular edema seems to reflect a generalized vascular leakage in type 2 diabetic patients.

Albuminuria↗

Increased heating efficiency of hyperthermia using an ultrasound contrast agent: a phantom study.

It is known that there are large temperature elevations in proximity to air bubbles during US (ultrasound) heating. The existence of tiny air bubbles in the target tissue may enhance the temperature elevation in US hyperthermia. To examine this hypothesis, phantom tissue experiments using an US contrast agent consisting of tiny air bubbles surrounded by a 5% (w/v) human albumin shell (Alb) were performed. As a phantom tissue, a 2 cm cube of beef was used. The phantom tissue was heated with or without the US contrast agent by an US hyperthermia device for 3 min. The heating device was operated at 1.5 MHz with the US intensity of 0.9 W/cm2. Physiological saline solution, iodized oil, and ethanol were used for control experiments. The effect of multiple needle punctures to the beef phantom was also examined. The temperature elevation rate (TER) was defined as the ratio of temperature elevation by heating with Alb or control materials to the temperature elevation by US heating alone. The TER of Alb was 1.7, whereas the TERs of the control materials and of the multiple needle punctures were approximately 1. The administration of Alb significantly increased the temperature in US hyperthermia. In addition, the heating efficiency of Alb was compared to the effect of an increase in the US intensity. Phantom tissue was heated at various US intensities. When the US intensity was increased from 0.9 to 1.8 W/cm2, the temperature elevated by approximately 1.7-fold. Thus, the effect of the administration of Alb was almost equivalent to the effect of increase in US power intensities from 0.9 to 1.8 W/cm2 in the present experimental settings. The results suggest that the US contrast agent can be a potential enhancer in US hyperthermia.

Hyperthermia, Induced↗

Myocardial fluid balance in acute hypertension.

OBJECTIVES: We hypothesized that (1) acute arterial hypertension increases myocardial microvascular fluid filtration and (2) the combination of acute arterial hypertension and coronary sinus pressure elevation may increase myocardial microvascular filtration sufficiently to estimate the osmotic reflection coefficient of the myocardial exchange vessels. METHODS: In nine mechanically ventilated dogs we cannulated the prenodal major cardiac lymph trunk. With the use of central venous phenylephrine infusion, mean arterial pressure (MAP) was raised progressively to 120, 160, and 180 mm Hg. In five dogs we additionally raised coronary sinus pressure (CSP) to 20 and 40 mm Hg. At each manipulation of MAP and/or CSP, we measured indexes of myocardial lymphatic function and lymph-to-plasma concentration ratios for total protein (CL(TP)/CP(TP) and albumin (CL(alb)/CP(alb)). RESULTS: Myocardial lymph flow rate (QL; microL/min) increased exponentially (QL = 10.9.e0.014.(MAP) and myocardial lymph driving pressure (PL; mm Hg) increased linearly (PL = 2.30 + 0.20 + 0.20 . MAP) following increases, whereas CL(TP)/CP(TP) and CL(alb)/CP(alb) decreases from 0.67 +/- 0.07 (SD) to 0.56 +/- 0.10 and from 0.91 +/- 0.05 to 0.75 +/- 0.11, respectively. Adding CSP elevation increased QL up to 12 times control associated with further CL(TP)/C(TP) and CL(alb)/CP(alb) decreases to 0.49 +/- 0.05 and 0.59 +/- 0.02, respectively. CONCLUSIONS: We conclude that hypertensive arterial pressures are, at least in part, transmitted to the myocardial microvascular exchange vessels in the intact animal leading to increased microvascular fluid filtration. However, the combination of acute arterial hypertension and coronary sinus pressure elevation is not sufficient to produce filtration independence required for myocardial osmotic reflection coefficient determination.

Animals↗

Differentiation of human umbilical cord blood stem cells into hepatocytes in vivo and in vitro.

AIM: To study the condition and potentiality of human umbilical cord blood stem cells (HUCBSC) to differentiate into hepatocytes in vivo or in vitro. METHODS: In a cell culture study of human umbilical cord blood stem cell (HUCBSC) differentiation, human umbilical cord blood mononuclear cells (HUCBMNC) were separated by density gradient centrifugation. Fibroblast growth factor (FGF) and hepatocyte growth factor (HGF) and the supernatant of fetal liver were added in the inducing groups. Only FGF was added in the control group. The expansion and differentiation of HUCBMNC in each group were observed. Human alpha fetoprotein (AFP) and albumin (ALB) were detected by immunohistochemistry. In the animal experiments, the survival SD rats with acute hepatic injury after carbon tetrachloride (CCL4) injection 48 h were randomly divided into three groups. The rats in group A were treated with human umbilical cord blood serum. The rats in group B were treated with HUCBMNC transplantation. The rats in group C were treated with HUCBMNC transplantation followed by intraperitoneal cyclophosphamide for 7 d. The rats were killed at different time points after the treatment and the liver tissue was histopathologically studied and human AFP and ALB detected by immunohistochemistry. The human X inactive-specific transcript gene fragment in the liver tissue was amplified by PCR to find human DNA. RESULTS: The results of cell culture showed that adherent cells were stained negative for AFP or ALB in control group. However, the adherent cells in the inducing groups stained positive for AFP or ALB. The result of animal experiment showed that no human AFP or ALB positive cells present in the liver tissue of group A (control group). However, many human AFP or ALB positive cells were scattered around sinus hepaticus and the central veins of hepatic lobules and in the portal area in group B and group C after one month. The fragment of human X chromagene could be detected in the liver tissue of groups B and C, but not in group A. CONCLUSION: Under certain conditions HUCBSC can differentiate into liver cells in vivo and in vitro.

Albumins↗

[Fluorescent labelling of rhodamine-labelled albumin in rabbit incisor dentine].

Incorporation of rhodamine-labelled serum albumin (R-ALB) into the developing dentine was investigated by fluorescent microscopy. Male Japanese white rabbits were injected with R-ALB at a dose of 50 mg/kg and the undecalcified section of the incisor dentine was obtained 11 days after the injection. The orange-red fluorescent labelling of R-ALB was observed in the internal dentine. The labelling consisted of several periodic stripes and decreased its intensity toward the predentine-dentine junction. Serum concentration of R-ALB rapidly decreased after the injection and 10% of the initial value was present after 12 hours. The concentration gradually decreased thereafter. No relationship was observed between the fluorescent labelling pattern and the change in the concentration of serum R-ALB. These results suggest that R-ALB fluorescent labelling is related to the diurnal dentine formation by the odontoblasts in the rabbit incisor.

Animals↗

Measurement of S-nitrosoalbumin by gas chromatography-mass spectrometry. I. Preparation, purification, isolation, characterization and metabolism of S-[15N]nitrosoalbumin in human blood in vitro.

S-Nitrosoalbumin (SNALB) and S-[15N]nitrosoalbumin (S[15N]ALB) were prepared by various methods, purified and isolated by a novel selective extraction procedure using HiTrapBlue Sepharose affinity columns and characterized by various techniques including SDS-PAGE electrophoresis, UV-Vis spectroscopy and gas chromatography-mass spectrometry (GC-MS). S-Nitrosylation of albumin in freshly obtained human plasma by unlabeled and 15N-labeled butylnitrite at neutral pH revealed the purest preparations. For GC-MS analysis, SNALB and S[15N]ALB were treated with HgCl2 to obtain nitrite and [15N]nitrite, respectively, which were then analysed as their pentafluorobenzyl derivatives. S[15N]ALB preparations were standardized by GC-MS using nitrite as internal standard. S[15N]ALB was prepared and isolated at concentrations of 188+/-43 microM (mean +/- SD, n = 8) at a final yield of about 45%, an isotopic purity of 98%, and SDS-PAGE electrophoretic purity of 90%. 15N-Labeled SNALB was used to study its metabolism in human blood. The half-life of S[15N]ALB (25 microM) in human heparinized blood in vitro was determined by GC-MS as 5.5 h. The GC-MS method described here could be useful for the quantitative determination of SNALB in human plasma using S[15N]ALB as an internal standard.

Blood↗

Quantification and characterization of protein loss in continuous ambulatory peritoneal dialysis.

BACKGROUND/AIMS: Dialysate protein loss is involved in the etiology of hypoalbuminemia and malnutrition on CAPD. There is no information regarding the peritoneal transport of proteins in neither Mexican nor LatinAmerican CAPD patients. Therefore, the aim of this study was to quantify and characterize the peritoneal membrane transport of albumin (Alb), IgG, IgA, and IgM in CAPD patients. In addition, factors associated to protein losses were investigated. METHODS: Thirty-seven CAPD patients were randomly selected and subjected to a standard peritoneal equilibration test (PET). Alb, IgG, IgA, and IgM were measured during the PET in both serum and dialysate. RESULTS: Dialysate IgM was not detected with the employed nephelometry method. A significant continuous and gradual increasing pattern in Alb, IgG and IgA losses was observed throughout the PET. During the PET, patients with the fastest transport type displayed the lowest serum concentration of Alb (but not Igs) and the greatest dialysate loss of all the assayed proteins. The strongest predictor for Alb, IgG, and IgA losses was peritoneal transport rate in both the univariate and multivariate analyses. CONCLUSIONS: Peritoneal Alb, IgG, and IgA losses in Mexican CAPD patients are mainly dependent on peritoneal transport rate and dialysate dwell-time.

Adult↗

[Directional development and differentiation of mouse embryonic stem cells into hepatocytes in vitro].

OBJECTIVE: To investigate the mechanism and regulation of differentiation from embryonic stem (ES) cells to hepatocytes in vitro and to find a new source of cell types for hepatocytes replacement therapies in the treatment of hepatic failure. METHODS: ES cells of BALB/c mice were cultured and maintained undifferentiated in gelatin-coated dishes in Dubecco's modified Eagle's medium (DMEM) containing 1 000 U/L leukaemia inhibitory factor (LIF). Then, the ES cells were cultured in DMEM without LIF so as to develop into embryonic bodies (EBs). For directional differentiating, EBs were put into 24-well tissue culture dish and differentiate into cells with different forms. On day 7 to day 11 acid fibroblast growth factor (aFGF) with terminal concentration of 100 ng/ml was added, and on day 11 to day 15 hepatocyte growth factor (HGF) terminal concentration of 20 ng/ml was added. EBs in culture without growth factor was used as controls. The development and differentiation status was observed by inversion microscope dynamically. The concentrations of alpha-fetoprotein (AFP) and albumin (ALB) in the supernatants were determined by radioimmunoassay on the 1st to 15th day since the ES cells were inoculated. Immunocytochemistry (ICC) was used to detect the expression of hepatic proteins such as AFP, ALB, cytokeratin 8 (CK8) and cytokeratin 18 (CK18) in the cells on the days 7, 8, 9, 10, 11, 12, 13, 14, and 15. The number of ALB positive cells was counted. The ALB positive rate was calculated as the differentiation ratio of hepatic cells. RESULTS: ES cells remained undifferentiated and grew to ES clones in the DMEM containing LIF and developed to EBs in the medium without LIF. AFP was detected firstly in the medium on day 8 with a concentration of 3.4 ng/ml and the concentration increased to be 22.8 ng/ml at day 15; ALB was detected firstly in the medium on day 11 with a concentration of 0.2 microg/ml and the concentration increased to be 2.2 microg/ml on day15. ICC showed that AFP, ALB, CK8, and CK18 began to be expressed on day 8, day 10, day 10, and day 11 respectively. The ICC-positive cells have the ultrastructures consistent with those of the normal mouse hepatocytes. The ratio of hepatic differentiation was 30%. CONCLUSION: ES cells can differentiate directionally into hepatocytes when cultured in gelatin-coated dish and medium with aFGF and HGF. This ES cell differentiating system provides enough functional hepatocytes and may be a good new source of differentiated cell types for hepatocytes replacement therapies in treatment of hepatic failure.

Albumins↗

The in vitro effect of albendazole, ivermectin, diethylcarbamazine, and their combinations against infective third-stage larvae of nocturnally subperiodic Brugia malayi (Narathiwat strain): scanning electron microscopy.

Scanning electron microscopy (SEM) was employed to observe the effects of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) alone, and the drugs in combination (ALB+IVM and ALB+DEC) against infective third stage larvae (L3) of nocturnally subperiodic (NSP) Brugia malayi (Narathiwat strain) in vitro. IVM, at a concentration of 10(-4) M, killed L3 within 1-2 h. The SEM data showed damage to the L3 surface and loss of regular cuticular annulations. The cuticles were grooved in the middle region of the body. In comparison with normal L3 before treatment with IVM, the cuticular surface showed transversed striations with periodic annulations. The result demonstrated that IVM showed a larvicidal activity against L3 of NSP B. malayi cultivated in vitro. Compared with those larvae in the control group, the treated larvae had no morphological changes in the cuticular surface at the head, body, and tail regions after cultivation with all drugs alone, and in their combinations at a concentration of 10(-5) M for 7 d. In this system, and at that concentration, only the larvae cultured with ALB alone remained highly motile. Although no morphological changes had been observed by SEM, those drugs used alone (IVM and DEC) and in combinations (ALB+IVM and ALB+DEC), reduced larval motility throughout the experiments at a concentration of 10(-5) M. The minimum lethal concentration (MIC) of IVM against NSP B. malayi was 10(-4) M.

Albendazole↗

[Human bone marrow multipotent adult progenitor cells differentiate into hepatocyte-like cells with hepatocyte growth factor plus fibroblast growth factor-4 in vitro].

OBJECTIVE: To investigate the possibility of the human bone marrow multipotent adult progenitor cells (hMAPCs) to differentiate into hepatocytes with hepatocyte growth factor (HGF)/ fibroblast growth factor-4 (FGF-4) in vitro. METHODS: (1) Obtaining the hMAPCs. Bone marrow was obtained from volunteers and then centrifuged through density gradient centrifugation methods. The collected mononuclear cells were cultured through adheret culture to get mesenchymal stem cells (MSCs). The hMAPCs were obtained through collecting and isolating the MSCs by magnetic activated cell sorting (MACS) through depletion selection by use of CD45 and GlyA microbeads. (2) Differentiation of the hMAPCs with HGF+FGF-4. Group A: HGF (20 ng/ml) + FGF-4 (10 ng/ml) induced hMAPCs; group B (positive control group): L-02 human hepatocytes(cell lines); and group C (negative control group): the undifferentiated hMAPCs. (3) The expressions of albumin (Alb), alpha fetoprotein (AFP), cytokeratin-18 (CK-18), and cytokeratin-19 (CK-19) were detected with immunocytochemistry to identify the characteristics of the differentiated cells at different times and the ratio of the positive cells was determined. (4) ALB, AFP, CK-18, and CK-19 expressions of the differentiated cells were detected by RT-PCR assay to investigate the mRNA transcriptions of characteristic hepatic proteins. (5) Alb expressions of the differentiated cells at different times were detected by Western blot on the 21st and 35th days. RESULTS: (1) The results of immunocytochemistry. The staining of Alb, CK18 were essentially positive in group A. As an early marker of immature hepatocytes, AFP staining was positive on the 7th day but negative in later differentiating periods in group A. (2) The results of RT-PCR. On the 7th day, the differentiated hMAPCs expressed AFP mRNA but were negative in later differentiating periods. On the contrary, the mRNA of Alb and CK-18 were positive at all times. (3) The results of Western blot assay. Alb protein was positive on the 21st day and 35th day. CONCLUSIONS: Under some definite inducing conditions hMAPCs can differentiate into hepatocyte-like cells. They may serve as a potential cell source for liver engineering.

Bone Marrow Cells↗

Pentafraction-Du Pont versus albumin for resuscitation of a lethal intestinal ischemic shock in rats.

This study compares the effect of pentafraction-Du Pont 6% (PF), albumin 5% (ALB), and Ringer's lactate (RL) on plasma volume (PV) expansion and survival in a lethal intestinal ischemic shock model. Shock was induced by exteriorizing the small intestines and occluding the mesenteric vessels for 75 min. Changes in PV were estimated using hematocrit (Hct). The solutions were administered continuously for 6 hr in volumes to maintain a stable Hct, or 15 ml/100 g body weight (bwt) for PF and ALB and 44 ml/100 g bwt for RL. Hct and bwt were measured hourly during the infusion and at 24 h. Untreated animals in shock developed hemoconcentration (Hct 62%) corresponding to a PV of 41% of baseline preshock level, with 9% (3/35) of the animals surviving 72 hr. RL expanded PV to 87% of preshock level, with a 57% (20/35) 72 hr survival rate and 46% (16/35) surviving greater than 7 days. Only 34% as much ALB was needed to induce a greater PV expansion of 101% with a 72 hr survival rate of 51% (18/35) and 46% (16/35) surviving greater than 7 days. When PF was used, PV expanded to 109% of preshock level with survival rates improving to 80% (28/35) at 72 hr and 71% (25/35) greater than 7 days compared to RL and ALB (P less than 0.05). There were no significant differences in survival rates between RL and ALB treated animals. We conclude that PF improves survival following intestinal ischemic shock compared to ALB and RL. PF is a safe and effective alternative to albumin for resuscitation in this shock model.

Albumins↗

[A study of glomerular damage due to extracorporeal circulation--meaning and usefulness of measuring of urinary microalbumin].

An increase of excretion of urinary microalbumin (U-Alb) is thought to demonstrate earlier glomerular damage than deterioration of Glomerular Filtration Rate (GFR). In this study, the meaning and usefulness of measuring U-Alb before, during and after Extracorporeal Circulation (ECC) was estimated. In 25 cases of adult cardiac surgery, we measured U-Alb, and simultaneously as current indices of glomerular function, serum and urinary creatinine, blood urea nitrogen, serum beta 2-microglobulin, urine volume, and cardiac output were measured. Albumin Excretion Rate (AER) [U-Alb X urine volume] and Albumin Index (AlbI) [U-Alb/U-Cr] were calculated as indices of U-Alb, and Creatinine clearance (Ccr) was calculated as GFR. The changes of each parameter, the correlation AER and AlbI during and after ECC with parameters that relate to ECC, and the assessment of the prolongation of glomerular damage after operation that possibly progress to acute renal failure were investigated. Our results showed AER and AlbI to increase following ECC with high values maintained during and after ECC, in spite of recovery of Ccr, from 24 hours to 4 days postoperatively. AER and AlbI recovered at 7 days and 14 days after surgery, respectively. The existence of glomerular damage, not indicated by a change in Ccr, was indicated by increases of AER and AlbI. The damage was thought to be temporary glomerular dysfunction. In correlation of AER and AlbI with ECC parameters, ECC of long duration influenced the glomerular damage as indicated by an increase of AER and AlbI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cellular expression of alpha-fetoprotein gene and its relation to albumin gene expression during rat azo-dye hepatocarcinogenesis.

During hepatocarcinogenesis, alpha-fetoprotein (AFP) synthesis may be dramatically increased while albumin synthesis is frequently decreased. Therefore, a reciprocal modulation between both gene expressions has been hypothesized. In this work, we combined in situ hybridization and immunoperoxidase on parallel liver tissue sections in order to analyze at the cellular level, AFP gene expression and its relation to ALB gene expression in both early and neoplastic lesions induced by 3MeDAB in the rat. In early lesions, cell populations were heterogenous as regards AFP expression. High levels of AFP transcripts were detected both in oval type cells and in a subset of basophilic hepatocytes within preneoplastic lesions. In these two highly AFP-expressing cell populations, significant levels of ALB transcripts were concomitantly detected. In the majority of altered hepatocytes, no AFP expression was detected while the level of ALB expression was decreased. In neoplastic lesions, AFP expression was strikingly heterogenous and independent from the degree of morphological differentiation. No evidence of reciprocal modulation with ALB gene expression could be assessed. In both preneoplastic and neoplastic lesions, a few altered hepatocytes displayed significant levels of AFP transcripts while no corresponding protein could be detected; such a discrepancy was not observed for ALB. This work shows that during 3MeDAB hepatocarcinogenesis, AFP gene activation occurs in heterogenous cell populations and according to different cellular patterns. Our observations lend no support to the hypothesis of a reciprocal modulation between AFP and ALB gene expressions during rat azo-dye hepatocarcinogenesis.

Albumins↗