Protection of chickens against experimental fowl typhoid using a nuoG mutant of Salmonella serotype Gallinarum

A nuoG mutation in NADH dehydrogenase I was introduced into a virulent strain of Salmonella serotype Gallinarum, the causative agent of fowl typhoid, using gene replacement with a nuoG open reading frame inactivated by insertion of DNA encoding a kanamycin resistance determinant. The S. Gallinarum nuoG mutant, named SG9NGK, was highly attenuated in chickens. SG9NGK colonized the caeca of chickens less efficiently than the S. Gallinarum parental strain, was less invasive and showed no evidence of multiplication in the liver or spleen. Using a single oral immunization with live bacteria SG9NGK reduced mortality in 2-week-old chickens following challenge with virulent S. Gallinarum from 75% to less than 8%.     

The influence of antenatal corticosteroids on hypoglycemia in newborn rats with intrauterine growth retardation

This study examines the effect of maternally injected glucocorticoid on the pattern of hypoglycemia exhibited by rat pups with intrauterine growth retardation (IUGR). The majority of surgical procedures designed to produce small-for-gestational age (SGA) newborns for biochemical studies were carried out on days 18 and 19 of gestation because of favorable vields of pups with IUGR at those operative days. At birth, normal controls showed a mean +/- SE plasma glucose value of 63 +/- 2 mg/dl; mean glucose for the group with IUGR was significantly lower at 43 +/- 2 mg/dl. There was a further decrease in the plasma glucose concentration of pups with IUGR at 2-4 hr of age, whereas values in the control littermates did not fall during this interval. Through the first 2 hr of neonatal life, 46% of the pups with IUGR exhibited plasma glucose values less than 40 mg/dl, whereas only 18% of the control littermates manifiested hypoglycemia. During the 2-4-hr interval, the incidence of hypoglycemia in animals with IUGR increased to 91%; however, the incidence in control remained at 18% from 2-4 hr and fell to 4% at 4-6 hr of age. At birth, the pups with IUGR had a lower mean liver weight compared to their control littermates, but glycogen concentration of liver was similar to the control mean +/- SE of 25.7 +/- 1.8 (IUGR = 22.2 +/- 1.3 mg/g wet weight). Total hepatic glycogen stores, however, were markedly lower in dysmature rat pups (IUGR = 2.96 +/- 0.17 mg; control = 7.23 +/- 0.43 mg). Concentrations of plasma glucose at birth of individual control and IUGR animals were found to correlate significantly (r = 0.64, p less than 0.001) with total liver glycogen content. The decline in plasma glucose values in pups with IUGR was not present in animals whose dams received glucocorticoid injection 24 and 48 hr before delivery. At 4-6 hr of age, for instance, the mean plasma glucose concentration in the corticoid-treated IUGR group (70.1 +/- 6.9 mg/dl) approximated that of the control group. Instead on the 91% incidence of hypoglycemia noted in the nontreated dysmature pups, an incidence of 55% was found at 2-4 hr of age in offspring of mothers given glucocorticoid. At 4-6 hr, the treated group showed an incidence of 18% compared to a 67% figure in the nontreated IUGR animals. The concentration of liver glycogen in these animals also differed in that the treated IUGR pups showed significantly higher values (26.9 +/- 1.7 mg/g wet weight, mean +/- SE) than nontreated progeny. It is concluded that antenatally administered corticosteroid influence the development of neonatal hypoglycemia in the dysmature rat pup and that the major effect is not at birth, but during the 2-4-hr period of neonatal life.     

Free and total malondialdehyde assessment in biological matrices by gas chromatography-mass spectrometry: what is needed for an accurate detection

A method to determine free and total (free and bound) malondialdehyde (MDA) in fresh human plasma, or in rat liver microsomes, using selected ion monitoring (SIM) gas chromatography-mass spectrometry in the electron impact mode was set up. The dideuterated internal standard, 3-hydroxy[1, 3-2H2]-2-propenal (dMDA), was added to the biological samples before their analytical manipulation. To detect free MDA the samples were reacted under mild conditions (25 degreesC, pH 4.0, 30 min) with phenylhydrazine (PH), affording 1-phenyl-1H-pyrazole and its 3, 5-dideuterated isotopomer. For the evaluation of total MDA level the plasma or microsomes were subjected, before the derivatization step, to hydrolysis in the presence of 1 M NaOH under preestablished conditions. This method offers several advantages such specificity, precision (within-day CV 2.0%, between-day CV 2.1%), linearity (0. 01-15 microM) and high sensitivity (5 pmol injected). The recovery of known added MDA amounts from plasma and microsomes, hydrolyzed or not, accounted for 98 +/- 0.6%. The free MDA levels found in the plasma and microsomes were 0.14 +/- 0.03 microM and 0.048 +/- 0.006 nmol/mg protein, respectively. The total MDA levels were 1.3 +/- 0. 07 microM in plasma and 0.36 +/- 0.04 nmol/mg protein in the microsomes.     

Hereditary neuralgic amyotrophy

Using a new ion-selective electrode, plasma concentration of ionized magnesium was measured in nine adult patients undergoing orthotopic liver transplantation. Baseline plasma ionized magnesium (IMg2+) concentration (0.49 +/- 0.07 mmol/L) was slightly below normal values (0.55-0.66 mmol/L, 95% CI): Six patients had ionized hypomagnesemia and two of these had total hypomagnesemia. Ionized IMg2+ concentration progressively decreased during the dissection (0.45 +/- 0.07 mmol/L, p < 0.05) and anhepatic stage (0.38 +/- 0.07 mmol/L, p < 0.05) and returned toward baseline values by 2 hours after graft reperfusion. Plasma ionized calcium levels and acid-base status were maintained within normal limits during surgery. Serum citrate concentration increased during the dissection (0.58 +/- 0.60 mmol/L) and anhepatic stages (1.18 +/- 0.78 mmol/L), the result of transfusion of citrate-rich blood products in the absence of adequate hepatic function, and gradually returned toward baseline values after graft reperfusion. IMg2+ concentration inversely correlated with the plasma citrate concentration (r2 = 0.54). The results of this study demonstrate that ionized hypomagnesemia invariably occurs during liver transplantation and suggest that this derangement may be a clinical concern, because magnesium is an important cofactor for the maintenance of cardiovascular homeostasis. The data further suggest the clinical importance of supplementation with magnesium based on the monitoring of plasma IMg2+ concentration.     

Change in serum hyaluronan: a simple index of short-term drug-induced changes in hepatic sinusoidal perfusion

BACKGROUND: Hyaluronan is an endogenous polysaccharide whose clearance from the plasma is predominantly by liver sinusoidal cells and is sinusoidal flow dependent. This study was designed to determine if a change in serum hyaluronan might reliably reflect short-term drug-induced changes in sinusoidal perfusion. METHODS: Hemodynamic changes following an oral dose of ketanserin were compared with changes in serum hyaluronan levels in 12 patients with alcoholic liver disease and portal hypertension. Indices determined comprised heart rate, mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance, hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and extraction, and total hepatic blood flow. Measurements were made in a basal state 1 hour after ketanserin ingestion and expressed as a ratio of values post- to pre-ketanserin administration. RESULTS: Ketanserin had variable effects comprising both increases and decreases in all indices. On univariate and multivariate analysis, changes in serum hyaluronan concentration (1.05 +/- 0.13, mean +/- SD) significantly correlated with only one index: changes in ICG clearance (0.93 +/- 0.17, r = -0.65, P = 0.02). CONCLUSIONS: Changes in serum hyaluronan levels reflect short-term drug-induced changes in sinusoidal perfusion in patients with alcoholic liver disease and portal hypertension. Serial measurement of serum hyaluronan levels may offer a simple method of screening vasoactive drugs for their short-term effects on sinusoidal perfusion.     

Observations on the transmissibility of lentogenic strains of Newcastle disease virus: significance of variables

Virus strain and age of chicken influenced the transmissibility of lentogenic strains of Newcastle disease virus (NDV). The ability of LaSota, B1, V4, CT, F, and Ulster strains to spread from cages of oronasally inoculated chickens to adjacent cages of susceptible chickens was assessed by virus isolation, serology, and immunity to challenge with virulent NDV. Although all inoculated chickens were immune to challenge, the immunity of contact chickens ranged from 100% for LaSota and CT strains to 0% for Ulster strain. The transmissibility of B1 and V4 strains for chickens 1, 4, 8, and 16 weeks old was assessed by within-cage contact infection, exposure to contaminated food and water containers, and exposure to air from infected chickens. Serology and immunity to challenge with virulent virus were used as criteria. Differences in transmissibility were observed for the strain of virus used, route of exposure, and age of chickens. Care must be used in interpreting the significance of strain differences until the effect of variables can be minimized by further improvements in design of the test procedure.     

Methods for estimating HIV prevalence: A comparison of extrapolation from surveys on infection rate and risk behaviour with back-calculation for the Netherlands

SUBJECTS AND METHODS: 227 of subjects with a 2-hour plasma glucose concentration of 120-199 mg/dl were selected from 413 participants who had two or more 75 g OGTT in health examinations from 1987-1995. From these subjects we established 8 groups according to initial 2-hour plasma glucose concentration 120-199 mg/dl stratified by 10 mg/dl, and calculated the total percentages of participants whose 2-hour plasma glucose concentration reached 200 mg/dl or greater over a 1-8 years (2.7 +/- 1.7 years, mean +/- SD) observation period. In 36 subjects who were tested annually over a four year period (4 times), the mean values of their 4 values were analyzed for relationships to coefficients of variation of the 2-hour plasma glucose. RESULTS: By stratified groups (from lowest to highest) of those with an initial plasma glucose concentration of 120-159 mg/dl, 7.4%, 12.1%, 16.1%, and 15.0% attained values of 200 mg/dl and higher, respectively in 1-8 years. On the other hand, 29.6%, 29.6%, 39.1%, and 47.4% of those with an initial plasma glucose concentration of 160-199 mg/dl moved to a diabetic type after 1-8 years, respectively. The percentages of those who ended up with levels of 200 mg/dl and greater at 2-hours tended to increase in subjects whose initial 2-hour plasma glucose concentration was over 160 mg/dl in comparison with patients below that initial level. CONCLUSIONS: From these results, it appears that subjects with 160-199 mg/dl 2-hour glucose concentration, which is considered a borderline status, are at high risk for future abnormal levels (> 200 mg/dl at 2-hours) and should be managed as a high risk level group for prevention of diabetes.     

Corticosteroid-binding globulin synthesis regulation by cytokines and glucocorticoids in human hepatoblastoma-derived (HepG2) cells

Plasma corticosteroid-binding globulin (CBG) concentrations decrease dramatically in patients with septic shock or burn injury. This decrease suggests that mediators of the acute phase response, such as cytokines and glucocorticoid hormones, might influence clearance as well as liver synthesis of CBG in humans. The present study investigated the effects of interleukin-6 (IL-6), IL-1 beta, and dexamethasone on CBG synthesis by a clone of human hepatoblastoma-derived (HepG2) cell line. In culture medium from HepG2 cells, the immunoconcentration of CBG and the levels of CBG messenger ribonucleic acid (mRNA) were dose dependently decreased in the presence of IL-6 concentrations ranging from 0.1-10 ng/mL. The percent decrease in CBG immunoconcentration was quantitatively similar to the percent decrease in CBG mRNA levels (29 +/- 6% and 39 +/- 15%, respectively, of control values). In contrast, and as expected, IL-6 dose dependently increased the mRNA levels (164 +/- 22% of control values) of alpha 1-antitrypsin, a positive acute phase protein, but did not affect the immunoconcentration of sex hormone-binding globulin, another liver protein. Dexamethasone alone did not significantly affect CBG secretion or mRNA levels, but did dose-dependently increase tyrosine amino-transferase mRNA levels, which increased to 252 +/- 16% of the control values. However, in combination with IL-6, dexamethasone had a significant additive effect on IL-6 inhibition of CBG secretion and mRNAs in HepG2 cells. IL-1 beta dose-dependently stimulated CBG secretion (156 +/- 10% of control values) with no significant effect on CBG mRNA levels. In addition, IL-1 beta significantly decreased the inhibitory effect of IL-6 on CBG secretion, but had no effect on the inhibitory effect of IL-6 on CBG mRNA levels. These results suggest that IL-1 beta acts on the posttranslation processing and/or secretion mechanisms of CBG in HepG2 cells. Together, the present results strongly support the hypothesis that the decrease in plasma CBG concentrations is associated with the increase in IL-6 and glucocorticoid levels reported in patients with septic shock and burn injury.     

Simultaneous flow cytometric measurement of Streptococcus suis phagocytosis by polymorphonuclear and mononuclear blood leukocytes

A simple flow cytometric method was used to study simultaneously the phagocytosis of Streptococcus suis serotype 2 by polymorphonuclear and mononuclear blood leukocytes from swine and humans. Using this method with a bacteria-to-leukocytes ratio of 10:1 and after 60 min of incubation, 80.2 +/- 2.8% of swine granulocytes and 77.0 +/- 2.8% of swine monocytes were shown to contain FITC-labelled S. suis serotype 2 strain 735. Using the same strain, FITC-labelled bacteria were found in 95.5 +/- 3.2% of human granulocytes and in 92.8 +/- 3.6% of human monocytes. The phagocytosis rates of avirulent and virulent strains of S. suis were not significantly different.     

Connections between the tendons of the musculus flexor digitorum profundus involving the synovial sheaths in the carpal tunnel

We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased in weight four times reaching 30% of the original liver mass, the transplant-bearing rats expired due to inability of the regenerating liver to support the rat.     

Influence of age and health on immune functions and trace elements

Apparently healthy elderly donors were screened according to a simple protocol that included clinical examination and the determination of hematological and biochemical values. This screening was performed to detect subclinical alterations which might interfere with immune responses and trace element status. The elderly were divided into two groups. The first group consisted of 22 (age 76 +/- 1 years) positively selected elderly (PSE), i.e. healthy subjects with no hematological and laboratory alterations, the second one comprised 13 (age 75 +/- 1 years) negatively selected elderly (NSE). Data were then compared with those obtained from 40 (age 35 +/- 2 years) healthy young controls. In both groups of elderly donors, plasma zinc levels were normal, while plasma copper concentrations were increased. Intracellular values of zinc and copper in mono- and polymorphonuclear cells from both groups of elderly were within reference limits. After in vitro activation, granulocyte chemiluminescence activity was impaired only in NSE. A decrement in the number of circulating CD3 lymphocytes and an increase in CD8d, CD57 cells were found in PSE, while NSE showed an increased number of CD3,DR cells and CD8d, CD57, CD8b,CD57 and CD16,CD56 positive cells. Our results indicate that only plasma copper levels were affected by age, whereas subclinical alterations in hematological or biochemical values appear to impair immune responses in the elderly.     

Human isosporiasis in an AIDS patient--report of first case in Malaysia

Splanchnic and systemic hemodynamics and plasma levels of aldosterone, glucagon and plasma renin were investigated in 12 patients with advanced cirrhosis before and 2 wk (14.6 +/- 2.8 days) and 2 mo (60.8 +/- 10.5 days) after orthotopic liver transplantation. Liver transplant was followed by significant (p < 0.01) changes in systemic hemodynamics at 2 wk, with a marked reduction in cardiac index (4.9 +/- 0.8 vs. 3.7 +/- 0.7 L/min.m2) and increases in mean arterial pressure (79 +/- 8 vs. 101 +/- 11 mm Hg) and peripheral vascular resistance (721 +/- 149 vs. 1,274 +/- 253 dyn.sec.cm-5). Two months after liver transplant, we saw further significant increases in peripheral vascular resistance (1,700 +/- 341 dyn.sec.cm-5; p < 0.05) without changes in cardiac index. Hepatic venous pressure gradient, very high before transplantation, was normal 2 wk after liver transplant (18.7 +/- 3.0 vs. 2.1 +/- 0.8 mm Hg; p < 0.01). Hepatic blood flow rose markedly from 1.03 +/- 0.46 to 2.25 +/- 0.79 L/min (p < 0.01) and was still elevated at 2 mo (1.84 +/- 0.74 L/min). Azygos blood flow had not changed after 2 wk with respect to pretransplant values (0.65 +/- 0.26 vs. 0.69 +/- 0.39 L/min) but had decreased significantly at 2 mo (0.39 +/- 0.16 L/min; p < 0.05). The elevated aldosterone, plasma renin and glucagon levels found in our cirrhotic patients before transplantation decreased to near-normal values 2 wk after the procedure. These results suggest that most of the hemodynamic and humoral abnormalities characteristic of advanced cirrhosis are reversed after liver transplant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of hepatocyte growth factor in the liver, kidney and lung following total body irradiation in rat

Hepatocyte growth factor (HGF) has been shown to have a pleiotropic function to act as a potent organotropic factor in the regeneration of injury in various organs, including the liver, kidney and lung. To examine the involvement of HGF in radiation injury, the authors analysed the changes in HGF mRNA and HGF protein levels in the rat organs (liver, lung, kidney) and plasma following 6 Gy of total body irradiation. Expression of HGF mRNA in the liver and kidney increased 6-48 h after total body irradiation and returned to previous values 1 week later. HGF protein levels in lung and liver showed 1.3-2-fold elevations 1-2 weeks after irradiation (P < 0.05). HGF levels in plasma stayed at undetectable levels up to 1 month after total body irradiation. The labelling index determined 2 weeks and 1 month after total body irradiation indicated no enhancement of regeneration. Thus, total body irradiation induced transient HGF elevation in these organs without enhancement of regeneration.     

Articular chondrocytes and synoviocytes in culture: influence of antioxidants on lipid peroxidation and proliferation

AIMS: Clozapine (CLZ), an atypical neuroleptic with a high risk of causing agranulocytosis, is metabolized in the liver to desmethylclozapine (DCLZ) and clozapine N-oxide (CLZ-NO). This study investigated the involvement of different CYP isoforms in the formation of these two metabolites. METHODS: Human liver microsomal incubations, chemical inhibitors, specific antibodies, and different cytochrome P450 expression systems were used. RESULTS: Km and Vmax values determined in human liver microsomes were lower for the demethylation (61 +/- 21 microM, 159 +/- 42 pmol min(-1) mg protein(-1) mean +/- s.d.; n = 4), than for the N-oxidation of CLZ (308 +/- 1.5 microM, 456 +/- 167 pmol min(-1) mg protein(-1); n = 3). Formation of DCLZ was inhibited by fluvoxamine (53 +/- 28% at 10 microM), triacetyloleandomycin (33 +/- 15% at 10 microM), and ketoconazole (51 +/- 28% at 2 microM) and by antibodies against CYP1A2 and CYP3A4. CLZ-NO formation was inhibited by triacetyloleandomycin (34 +/- 16% at 10 microM) and ketoconazole (51 +/- 13% at 2 microM), and by antibodies against CYP3A4. There was a significant correlation between CYP3A content and DCLZ formation in microsomes from 15 human livers (r=0.67; P=0.04). A high but not significant correlation coefficient was found for CYP3A content and CLZ-NO formation (r=0.59; P=0.09). Using expression systems it was shown that CYP1A2 and CYP3A4 formed DCLZ and CLZ-NO. Km and Vmax values were lower in the CYP1A2 expression system compared to CYP3A4 for both metabolic reactions. CONCLUSIONS: It is concluded that CYP1A2 and CYP3A4 are involved in the demethylation of CLZ and CYP3A4 in the N-oxidation of CLZ. Close monitoring of CLZ plasma levels is recommended in patients treated at the same time with other drugs affecting these two enzymes.     

Decreased production and increased catabolism of apolipoprotein B-100 in apolipoprotein B-67/B-100 heterozygotes

Apolipoprotein (apo) B-67 is a truncated form of apoB-100 due to deletion of an adenine at cDNA 9327. Heterozygotes have one allele making apoB-100; therefore, plasma apoB levels would be predicted to be at least 50% of normal. However, apoB-67 heterozygotes have total plasma apoB levels that are 24% of normal. To determine the mechanisms responsible for the lower-than-expected levels of apoB, in vivo kinetics of apoB-100 were performed in three apoB-67/apoB-100 heterozygotes and compared with those of six control subjects by using a primed-constant infusion of [5,5,5-2H3]leucine in the fed state. Kinetic parameters were calculated by multicompartmental modeling of the data. The mean total apoB plasma concentration of the apoB-67 subjects was 21.8+/-6.1 mg/dL, or 24% of that of control subjects (89.6+/-24.1 mg/dL, P=.002). ApoB-67 subjects had lower mean VLDL apoB-100 production rates (3.6+/-1.2 versus 13.9+/-3.5 mg x kg(-1) x d(-1), P=.002) and lower mean transport rates of apoB-100 into LDL (3.5+/-1.4 versus 12.6+/-4.1 mg x kg(-1) x d(-1), P=.008) compared with control subjects. The transport rate into IDL was not significantly different (1.2+/-0.5 versus 6.2+/-4.0 mg x kg(-1) x d(-1), P=.07). The fractional catabolic rate of VLDL apoB-100 was significantly higher in apoB-67 subjects than in control subjects (18.1+/-8.6 versus 7.6+/-1.6 mg x kg(-1) x d(-1), P=.017). ApoB-100 IDL and LDL fractional catabolic rates were not significantly different. VLDL apoB-100 pool size in apoB-67 subjects was 11% of that of control subjects (15.8+/-7.7 versus 141.6+/-33.7 mg, P=.0004) due to a 74% lower production rate (26% of control values) and a 2.4-fold higher fractional catabolic rate. LDL apoB-100 pool size in apoB-67 subjects was 22% of that of control subjects (665.3+/-192.4 versus 2968.3+/-765.2 mg, P=.002) due primarily to a lower production rate (27% of control values). Thus, both decreased production of VLDL and LDL apoB-100 and increased catabolism of VLDL apoB-100 are responsible for the low levels of apoB-100 in apoB-67 subjects.     

Using ethnography to investigate life scientists'' information needs

Although several liver diseases of childhood, particularly biliary atresia (BA) and cystic fibrosis (CF) liver disease (CFLD) are characterized by hepatic fibrosis, the pathogenesis of this process is incompletely understood. The cytokine transforming growth factor-beta1 (TGF-beta1) has been implicated in hepatic fibrosis in experimental animals, in which both the hepatic expression and plasma concentration of this cytokine are increased. The objective of our study was to determine whether there are similar alterations of TGF-beta1 in patients with hepatic fibrosis secondary to either BA and/or CFLD. The study design was as follows. In study 1, plasma TGF-beta1 was assessed by ELISA in 9 children with BA undergoing liver transplantation, 11 patients with CFLD, and appropriate control subjects. In study 2, hepatic expression of TGF-beta1 protein (assessed immunohistochemically) and hepatic fibrosis were scored semiquantitatively, on a 1-3 scale, by blinded investigators, in archival liver biopsy specimens from 10 children with BA, 10 with CFLD, and from 10 older children with normal hepatic histology, as well as in 4 patients with liver diseases of various etiologies. Simultaneous plasma and liver TGF-beta1 studies were performed in 8 patients with liver disease. Results were as follows. Plasma TGF-beta1 values were inversely correlated with age in healthy subjects (r=-0.54, p < 0.0001). The plasma TGF-beta1 protein of children with BA was decreased (13+/-2 ng/mL) compared with values for healthy children (42+/-6 ng/mL, n=10, p < 0.005). Similarly, the plasma TGF-beta1 concentration in patients with CFLD was also decreased compared with values for children with CF and normal serum liver profiles (n=14) (2+/-1 ng/mL versus 12+/-1, p < 0.05). However, the plasma TGF-beta1 concentration was increased in two patients with other types of liver disease. The hepatic expression of TGF-beta1 was increased in the presence of hepatic fibrosis in all types of liver diseases studied. Forty-six percent of patients had both marked hepatic fibrosis and marked TGF-beta1 labeling; 86% of samples without fibrosis showed no TGF-beta1 labeling, p=0.007. In conclusion, these studies have established the association of hepatic TGF-beta1 protein and hepatic fibrosis in several common liver diseases of childhood. Our data also suggest that, in children, plasma TGF-beta1 does not appear to be a useful marker of hepatic expression of this cytokine.     

Endothelin 1-21 plasma levels on the first and fourth postpartum day in normal full-term neonates

Endothelins (ETs), recently discovered and highly vasoactive substances, have been implicated in the pathogenesis of various perinatal problems, such as preeclampsia, intrauterine growth retardation, intraventricular hemorrhage, pulmonary hypertension and necrotizing enterocolitis. Although fetal ET levels have been measured at birth, reference ET values for healthy newborns in the first days of life have not been established. The purpose of this study was to determine in normal healthy neonates ET 1-21 plasma values on day 1 and 4 postpartum and to investigate possible changes after adaptation of the newborn to extrauterine life. The study comprised 20 healthy full-term neonates, born after vaginal delivery (n = 10), or cesarean section (CS; n = 10) because of a previous CS. Venous blood was drawn on day 1 and 4 from all neonates and ET 1-21 levels were determined in the plasma by radioimmunoassay (Amersham kit RPA 5559). ET 1-21 values were on day 1 11.83 +/- 2.39 pmol/l (n = 20) and on day 4 9.45 +/- 1.88 pmol/l (n = 20). The statistical analysis showed a significant reduction of plasma ET levels on day 4 (p = 0.004), but no influence of the mode of delivery on plasma ET levels. In conclusion irrespective of the mode of delivery the high ET 1-21 plasma levels on day 1 postpartum are significantly reduced on day 4 of life.     

Blood pressure levels in diabetes mellitus

Levels of fasting plasma glucose, body mass index, serum total lipids, serum total cholesterol, serum triglycerides and blood pressure of 177 Libyan diabetic patients were determined. The respective mean values were 212.4 +/- 5.6 mg/dl, 26.6 +/- 0.45 kg/m2, 825.7 +/- 20.5 mg/dl, 176.4 mg/dl, 144 +/- 5.8 mg/dl and 135.3 +/- 1.7/83 +/- 0.89 mm Hg. The mean levels of all variables except plasma glucose are significantly higher in the female patients than their male counterparts. Correlations were present between blood pressure levels and age/body mass index/serum total lipids. There was a significant correlation between systolic pressure levels and the duration of diabetes. Serum cholesterol and serum triglyceride levels correlated with diastolic blood pressure levels only.     

Plasma levels of atrial natriuretic peptide and brain natriuretic peptide following intravenous saline infusion in oedematous chronic obstructive pulmonary disease and non-oedematous chronic obstructive pulmonary disease

Some patients with chronic obstructive pulmonary disease (COPD) develop oedematous COPD (oCOPD) with peripheral oedema and have a poor prognosis. The cause of the fluid retention is poorly understood but could be due to defective release of a natriuretic factor. We investigated this hypothesis by measuring levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) before and after a 0.1 ml/kg/min 2.7% saline infusion in 6 patients with hypoxemic COPD but no history of oedema and 7 COPD patients with oCOPD. Vasopressin, aldosterone, plasma and urinary urea and electrolytes and osmolality were measured. Arterial blood gases and spirometry were also recorded. The two groups were similar in terms of age, weight, PaO2, PaCO2 and FVC. FEV1 was significantly lower in the oCOPD group. The oCOPD group excreted less urine (202 +/- 23 vs. 364 +/- 48 ml; p < 0.05) and less sodium (32 +/- 3 vs. 68 +/- 9 mmol/l; p < 0.01) as a percentage of the saline load given (18 +/- 2 vs. 30 +/- 4%; p < 0.05). Pre-infusion BNP and ANP levels were similar in both groups. BNP and ANP had an exaggerated increase in the oCOPD group on saline loading. In the oCOPD group, ANP levels were significantly greater 1 h after the saline load compared to the pre-infusion values (30 +/- 7 vs. 11 +/- 2; p < 0.05). BNP did not reach significantly greater levels than baseline values until 3 h after the infusion had ended (45 +/- 6 vs. 27 +/- 2; p < 0.05). At 1 h after the saline load, BNP and ANP levels were significantly greater in the oCOPD group (BNP 32 +/- 2 vs. 24 +/- 1; p < 0.01 and ANP 30 +/- 7 vs. 7 +/- 2; p < 0.05) when compared to COPD controls. BNP levels remained significantly different from the COPD control group 3 h after the infusion ended (45 +/- 6 vs. 26 +/- 2; p < 0.05). Although aldosterone levels were greater in the oCOPD group before the saline infusion, the hormone level was suppressed appropriately by the infusion. In conclusion, the cause of oedema in oCOPD and the inability to excrete a saline load is not due to a failure of release of BNP or ANP.