High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome

Activation of endothelin receptors on the vasculature can produce a variety of responses from potent vasoconstriction to mild vasodilation, depending on the receptor complement within the tissue. To elucidate the potential role of endothelin analogues as tumour blood flow modifiers, we have evaluated the effect of the ET(B) receptor agonist, IRL 1620 ([Suc-(Glu9, Ala(11,15))-ET-1(8-21)]) in CBH/CBi rats bearing an HSN fibrosarcoma. Tissue blood flow and vascular resistance were determined, 20 min following administration of IRL 1620 (bolus intravenous), using the uptake of radiolabelled iodoantipyrine (125I-IAP). Blood flow was unchanged in most tissues. However, at doses > or = 1.0 nmol kg(-1) IRL 1620, blood flow in the brain and heart was increased, whereas in the small intestine it was reduced. Blood flow in the skeletal muscle was reduced at 1.0 nmol kg(-1) only. Tumour blood flow was significantly reduced at 3.0 and 5.0 nmol kg(-1). Vascular resistance was unchanged in most tissues although it was increased in the skeletal muscle at 1.0 nmol kg(-1), in the kidney at 1.0 and 3.0 nmol kg(-1) and in the brain and heart, it was reduced at 5.0 nmol kg(-1) IRL 1620. Vascular resistance was significantly increased in the tumour and the small intestine at doses > or = 1 nmol kg(-1) IRL 1620. Pretreatment of rats with BQ-788, an ET(B) receptor antagonist, selectively attenuated the tumour vascular response to 3 nmol kg(-1) IRL 1620 with no changes observed in the normal tissue responses. Our results demonstrate that the HSN tumour vasculature is selectively responsive to IRL 1620 at doses > 1 nmol kg(-1) compared with the majority of normal tissues with the exception of the small intestine, and that only the tumour response is highly sensitive to BQ-788 antagonism, under the experimental dosing regime investigated. These differences may be exploitable for therapeutic benefit.     

Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: changes in pulmonary hypertension

Phosphodiesterase (PDE) activity was determined in pulmonary arteries removed from control and chronic hypoxia-induced pulmonary hypertensive rats. The main, first-branch, intrapulmonary and resistance pulmonary arteries were studied. We measured total cAMP PDE activity and cGMP PDE activity, as well as that of individual isoforms (PDE1-5). cAMP PDE activity in chronic hypoxic rats was increased in first-branch and intrapulmonary arteries from hypoxic rats. No changes were observed in the main or resistance pulmonary arteries. Similarly, cGMP PDE activity was increased in the main, first-branch and intra-pulmonary arteries of the hypoxic rats. No changes in cGMP PDE activity were observed in resistance arteries. There was evidence for PDE1-5 activity in all pulmonary arteries. The increased cAMP PDE activity in first-branch and intrapulmonary vessels was associated with an increase in cilostimide-inhibited PDE (PDE3) activity. Increased total cGMP PDE in main pulmonary artery was associated with increases in Ca++/calmodulin-stimulated (PDE1) activity. An increase in zaprinast-inhibited (PDE5) activity was observed in first-branch and intrapulmonary arteries. Our results suggest that decreases in intracellular cyclic nucleotide levels in pulmonary arteries from pulmonary hypertensive rats are associated with increased PDE activity. Further, these changes may reflect alterations at the level of specific types of PDE isoforms.     

Advanced practice nursing in Texas: the interface of accreditation, regulation, and certification

The rapidity and degree of development of regulation by boards of nursing of advanced practice nurses (APNs) and programs for their preparation has varied from state to state over the past 20 years. In general, boards have authority only to regulate advanced practice through the recognition of APNs and the setting of standards and scope of their practice. In the early 1990s, lack of consistent APN educational program standards and experiences and criteria for recognition of APNs was problematic at the levels of accreditation, certification, and regulation. The interdependency of these concepts as well as the necessity and difficulty of linking them in a consistent, effective manner has become increasingly evident. The Texas Board of Nurse Examiners has been involved in deriving a model designed to ensure the education and recognition of APNs with emphasis on both professionalism and public safety. Because Texas is unique in size and geography, it mirrors many problems and issues of both large and small states.     

Human embryonic spinal cord grafts in adult rat spinal cord cavities: survival, growth, and interactions with the host

The ability of solid pieces of transplanted human embryonic spinal cord to survive, grow, and integrate with adult rat host spinal cord tissue was investigated. Unilateral cavities were surgically created at vertebral level T12-T13 in 10 athymic nude rats and 5 regular Sprague-Dawley rats. Seven of the athymic rats acutely received a human spinal cord graft, while the remaining 8 rats served as controls, with cavities alone. After 6 months the morphological outcome was evaluated with cresyl violet and with immunohistochemistry using antibodies toward human-specific neurofilament (hNF), human-specific Thy-1 (Thy-1), neurofilament, glial fibrillary acidic protein, serotonin (5-HT), and tyrosine hydroxylase (TH). The in situ morphology of the human embryonic spinal cord was also investigated and compared with grafts that were six months older. Solid human embryonic spinal cord grafts showed a 100% survival rate, grew to fill the volume of the cavity in a noninvasive manner, and expressed human specific antigens 6 months postgrafting. Thy-1 immunoreactivity (IR) was demonstrated up to 8 mm rostral to the graft suggestive of graft-derived fiber outgrowth. hNF-IR fibers and 5-HT- and TH-IR fibers traversed the graft-host border for a few hundred micrometers, respectively. Finally, our findings suggest that grafted solid pieces of human embryonic spinal cord minimize cystic deformations seen in the adult rat spinal cord with a unilateral cavity.     

RT1-U: identification of a novel, active, class Ib alloantigen of the rat MHC

In common with other mammalian species, the laboratory rat (Rattus norvegicus) expresses MHC class I molecules that have been categorized as either classical (class Ia) or nonclassical (class Ib). This distinction separates the class Ia molecules that play a conventional role in peptide Ag presentation to CD8 T cells from the others, whose function is unconventional or undefined. The class Ia molecules are encoded by the RT1-A region of the rat MHC, while the RT1-C/E/M region encodes up to 60 other class I genes or gene fragments, a number of which are known to be expressed (or to be expressible). Here we report upon novel MHC class Ib genes of the rat that we have expression cloned using new monoclonal alloantibodies and which we term RT1-U. The products detected by these Abs were readily identifiable by two-dimensional analysis of immunoprecipitates and were shown to be distinct from the class Ia products. Cellular studies of these molecules indicate that they function efficiently as targets for cytotoxic killing by appropriately raised polyclonal alloreactive CTL populations. The sequences of these class Ib genes group together in phylogenetic analysis, suggesting a unique locus or family. The combined serological, CTL, and sequence data all indicate that these products are genetically polymorphic.     

Biotransformation of 2-chloroaniline in the Fischer 344 rat: identification of urinary metabolites

1. The biotransformation of a single i.p. dose of [14C]2-chloroaniline (1.0 mmol/kg, approximately 60 microCi/rat) was investigated in the urine and faeces of the male Fischer 344 rat. 2. During 24 h, 53.1% of the administered radioactivity was eliminated into the urine, while < 1% of the radioactivity appeared in the faeces. 3. The major biotransformation pathways were para-hydroxylation and sulphate conjugation. 4-Amino-3-chlorophenyl sulphate was the major urinary metabolite comprising 31.6% of total urinary radioactivity. The para-hydroxylated metabolite, 4-amino-3-chlorophenol (10.8%), and its O-glucuronide conjugate (3.7%) were also urinary metabolites. The formation of direct conjugates of 2-chloroaniline, the N-sulphate and N-glucuronide, was significant with as much as 18.6 and 8.6%, respectively, of these metabolites excreted in the urine. The parent compound, 2-chloroaniline, accounted for 16.9% of urinary radioactivity. 4. N-Acetylated products were minor metabolites present in urine as 2-chloro-4-hydroxyacetanilide and its sulphate or glucuronide conjugate. Neither 2-chloroacetanilide nor its oxidation products, 2-chloroglycolanilide and 2-chlorooxanilic acid, were urinary metabolites.     

Endothelin receptors mediating contraction of rat and human pulmonary resistance arteries: effect of chronic hypoxia in the rat

1. We examined the endothelin (ET) receptors mediating contractions to ET-1, ET-3 and sarafotoxin S6c (SX6c) in rat pulmonary resistance arteries by use of peptide and non-peptide ET receptor antagonists. Changes induced by pulmonary hypertension were examined in the chronically hypoxic rat. The effect of the mixed ET(A)/ET(B) receptor antagonist SB 209670 on endothelin-mediated contraction was also examined in human pulmonary resistance arteries. 2. In rat vessels, the order of potency for the endothelin agonists was SX6c = ET-3 > ET-1 (pEC50 values in control rats: 9.12+/-0.10, 8.76+/-0.14 and 8.12+/-0.04, respectively). Maximum contractions induced by ET-3 and ET-1 were increased in vessels from chronically hypoxic rats. 3. The ET(A) receptor antagonist FR 139317 (1 microM) had no effect on the potency of ET-1 in any vessel studied but abolished the increased response to ET-1 in the chronically hypoxic vessels. The ET(A) receptor antagonist BMS 182874 (1 microM) increased the potency of ET-1 in control rat vessels without effecting potency in the pulmonary hypertensive rat vessels. 4. Bosentan (non-peptide mixed ET(A)/ET(B) receptor antagonist) increased the potency of ET-1 in control rat vessels but was without effect in the pulmonary hypertensive rat vessels. Bosentan (1 microM) inhibited responses to SX6c in control and chronically hypoxic rat vessels with pKb values of 5.84 and 6.11, respectively. The ET(B) receptor antagonist BQ-788 (1 microM) did not inhibit responses to ET-1 in any vessel tested but did inhibit responses to both SX6c and ET-3 (pKb values in control and chronically hypoxic rat vessels respectively: SX6c 7.15 and 7.22; ET-3: 6.68 and 6.89). BQ-788 (1 microM) added with BMS 182874 (10 microM) did not inhibit responses to ET-1 in control vessels but caused a significant inhibition of responses to ET-1 in chronically hypoxic preparations. 5. SB 209670 inhibited responses to ET-1 in both control and chronically hypoxic vessels with pKb values of 7.36 and 7.39, respectively. SB 209670 (0.1 and 1 microM) virtually abolished responses to ET-1 in the human pulmonary resistance artery. 6. In conclusion, in rat pulmonary resistance arteries, vasoconstrictions induced by ET-1, SX6c and ET-3 are mediated predominantly by activation of an ET(B)-like receptor. However, lack of effect of some antagonists on ET-1 induced vasoconstriction suggests that ET-1 stimulates an atypical ET(B) receptor. The increase in potency of ET-1 in the presence of some antagonists suggests the presence of an inhibitory ET(A)-like receptor. The influence of this is reduced, or absent, in the chronically hypoxic rats. Increased responses to ET-1 are observed in the chronically hypoxic rat and may be mediated by increased activation of ET(A) receptors. SB 209670 is unique in its potency against responses to ET-1 in both control and chronically hypoxic rats, as well as human, isolated pulmonary resistance arteries.     

Autotransplantation of the spleen in the rat: donor leukocytes of the splenic fragment survive implantation to migrate and proliferate in the host

A rabbit liver UDP-glucuronosyltransferase cDNA that is related to human and rat UGT1A7 has been identified. The predicted amino acid sequence of the UGT1A71 displays 80% similarity to that encoded by human HP4 (UGT1A9), but 81% to that predicted for human UGT1A7 and 77% to the rat UGT1A7 (UGTA2). The exons encoding human UGT1A7 and rat UGTA2 are the seventh of the series of cassette exons that flank the 3' common exon series of the UGT1A locus. Southern blot analysis demonstrates that the exon sequence encoding UGT1A71 is part of a larger cluster of highly related genes. The UGT1A71 RNA is expressed in both neonatal and adult liver, and unlike rat UGT1A2 which is inducible with Ah receptor ligands such as polycyclic aromatic hydrocarbons, rabbit UGT1A7 is not regulated when animals are exposed to these inducers. Following expression of UGT171 in COS-1 cells, glucuronidation activity was identified for small phenolic molecules like 4-nitrophenyl, bulky phenols as represented by 4-hydroxybiphenol and octylgallate, as well as 4-hydroxyestrone. In addition, UGT1A71 possesses catalytic activity toward tertiary amines like the tricyclic antidepressant imipramine. The pattern of UGT1A71 glucuronidation is similar to that observed for human UGT1A9, except tertiary amines are not subject to glucuronidation by human UGT1A9. Glucuronidation of tertiary amines is catalyzed principally by human UGT1A4 as well as rabbit UGT1A4. Although rabbit UGT1A7 catalyzes the formation of quarternary ammonium glucuronides, the Vmax is considerably less than that observed for rabbit UGT1A4. Overall, the characterization of rabbit UGT1A7 suggests that this protein represents the ortholog of the human UGT1A7, which to date has not been identified.     

Detection of Echinococcus multilocularis in the definitive host: coprodiagnosis by PCR as an alternative to necropsy

Recently, extensions of the range of Echinococcus multilocularis in Europe and North America and drastic increases in fox populations in Europe put an increasing proportion of the human population at risk of alveolar echinococcosis. To obtain data on the local infection pressure, studies of the prevalence of the parasite in the animals that transmit the parasite, foxes, dogs, and cats, are urgently required. Such investigations, however, have been hampered by the need for necropsy of the host animal to specifically diagnose infection with the parasite. In this study, a nested PCR and an improved method for DNA extraction were developed to allow the sensitive and specific diagnosis of E. multilocularis infections directly from diluted fecal samples from foxes. The target sequence for amplification is part of the E. multilocularis mitochondrial 12S rRNA gene. The specificity of the method was 100% when it was tested against 18 isolates (metacestodes and adult worms) of 11 cestode species, including E. granulosus. The sensitivity of the method was evaluated by adding egg suspensions and individual eggs to samples of diluted feces from uninfected foxes. The presence of one egg was sufficient to give a specific signal. To confirm the PCR results, an internal probe which hybridized only with E. multilocularis amplification products but not with the DNA of other cestodes was constructed. In order to investigate the applicability of this method for epidemiological studies, 250 wild foxes from a area in southern Germany where echinococcosis is highly endemic were examined by both necropsy and PCR of rectal contents. The sensitivity correlated with the parasites' number and stage of maturity. It ranged from 100% (>1,000 gravid worms) to 70% (<10 nongravid worms). On the basis of positive PCR results for 165 foxes, the sensitivity of the traditional and widely used necropsy method was found to be not higher than 76%. We therefore present this PCR system as an alternative method for the routine diagnosis of E. multilocularis in carnivores.     

Birth weight, adult weight, and girth as predictors of the metabolic syndrome in postmenopausal women: the Rancho Bernardo Study

OBJECTIVE: Recent studies have demonstrated an association between low birth weight and chronic and metabolic disorders in adulthood such as type 2 diabetes, hypertension, and dyslipidemia. These disorders tend to cluster in a condition known as the metabolic syndrome (syndrome X). Only two studies have reported an association of birth weight to the metabolic syndrome. The present study is distinguished as the only study to focus on postmenopausal women. RESEARCH DESIGN AND METHODS: Subjects were 303 community-dwelling, postmenopausal Caucasian women aged 50-84 years. Metabolic and anthropometric variables were measured at a clinic visit; birth weight was assessed by self-report on a mailed questionnaire. RESULTS: The metabolic syndrome, defined as the simultaneous presence of hypertension, dyslipidemia, and abnormal glucose tolerance, was present in 7.9% of these women. Compared with women in the highest birth weight tertile (8.1-13.0 lb, mean 9.4 lb), those in the lowest birth weight tertile (2.5-6.8 lb, mean 5.5 lb) exhibited an increased prevalence (12.0 vs. 4.3%, P < 0.05) and 2.41 times the risk (95% CI 1.06-5.51) of developing the metabolic syndrome. Women with a heavy birth weight had an increased risk of adult obesity. Nevertheless, women in the lowest birth weight tertile who became adults in the highest tertile of BMI (>25.2 kg/m2) or waist circumference (>80.7 cm) had the highest prevalence of the metabolic syndrome (approximately 30%). CONCLUSIONS: Low birth weight coupled with adult obesity is a strong determinant of the metabolic syndrome in postmenopausal women.     

Old-age deficits in the sense of smell as gauged by thresholds, magnitude matching, and odor identification.

Twenty elderly subjects (70–90 years old) and 20 young control subjects (18–24 years old) underwent three kinds of olfactory testing: absolute thresholds to three odorants (d-limonene, iso-amyl butyrate, benzaldehyde), magnitude matching of these odorants to salt tastes, and odor identification of 30 common substances. For all three odorants elderly subjects' mean threshold significantly exceeded that of the young by about nine-fold for d-limonene, about three-fold for benzaldehyde, and about two-fold for iso-amyl butyrate. These threshold differences predict approximate concentration differences necessary to arouse the same estimated odor strength above the threshold for the elderly and the young. Young subjects also scored better than the elderly in odor identification, even when subjects were given four alternatives from which to select the correct label. Unimpaired olfactory functioning is uncommon in the elderly; correlational tests show that as a group the young have better olfactory ability and show more interindividual uniformity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase I metabolites and glutathione conjugates

Sulforaphane (SFN) is a naturally occurring isothiocyanate present in cruciferous vegetables, such as broccoli, that has been identified as a potent inducer of glutathione S-transferase activities in laboratory animals. The present studies were carried out to elucidate the metabolic fate of SFN in the rat. Particular emphasis was placed on glutathione (GSH)-dependent pathways because conjugation with GSH is a major route by which many isothiocyanates are eliminated in mammals. Male Sprague-Dawley rats were administered a single dose of SFN (50 mg kg-1 ip), and bile and urine were collected over ascorbic acid. Analysis of biological fluids was carried out by ionspray LC-MS/MS using the neutral loss (129 Da) and precursor ion (m/z 164) scan modes to detect GSH and N-acetylcysteine (NAC) conjugates, respectively. In bile, five thiol conjugates (designated M1-M5) were detected. Metabolites M2 and M4 were identified as the GSH conjugates of SFN and erucin (ERN, the sulfide analog of SFN), respectively, by comparing their LC-MS/MS properties with those of standards obtained by synthesis. M1 was characterized as the GSH conjugate of a desaturated metabolite of SFN (tentatively assigned the structure of delta 1-SFN), suggesting that the parent compound also undergoes oxidative metabolism. Metabolites M3 and M5 were identified as the NAC conjugates of SFN and ERN, respectively, and together with the NAC conjugate of delta 1-SFN, these species also were detected in urine. Quantitative determination of the former two mercapturates in urine indicated that approximately 60% and approximately 12% of a single dose of SFN is eliminated in 24 h as the NAC conjugates of SFN and ERN, respectively. The corresponding figures in rats dosed with ERN were approximately 67% and approximately 29%. When the GSH conjugate of SFN was incubated with phosphate buffer (pH 7.4, 37 degrees C), < 1% of the conjugate dissociated to liberate free SFN. On the other hand, the conjugate underwent a facile thiol exchange reaction (> 70% conversion) when incubated in the presence of excess cysteine, thereby acting as an effective carbamoylating agent. It is concluded that SFN undergoes metabolism by S-oxide reduction and dehydrogenation and that GSH conjugation is the major pathway by which the parent compound and its phase I metabolites are eliminated in the rat.     

The VIPoma: further confirmation of VIP as the hormonal agent in the WDHA syndrome

The WDHA syndrome characterized by watery diarrhea, hypokalemia, and achlorhydria is being diagnosed with increasing frequency. The diagnosis has been made to date only due to severe clinical symptomatology. In a review of the literature gastrin, secretin, glucagon, enteroglucagon, gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP), and prostaglandins have been variously suggested as a possible etiologic agent for this syndrome. A case of the WDHA syndrome is reported in which hormonal assays of the serum preoperatively and two years postoperatively and tumor for many of the proposed agents is performed. A discussion of possible cross-reactivity among these similary structured polypeptides in the radioimmunoassays systems is used to explain the multitude of possible hormonal agents presented in the literature. Standardization of the VIP assays will result in increasing diagnosis of this diseases state prior to its fulminant clinical presentation.     

Fibronectin in host defense: implications in the diagnosis, prophylaxis and therapy of infectious diseases

A polymerase chain reaction (PCR) was developed for the detection of Clostridium botulinum type A, a cause of human botulism. A two primer set and an oligonucleotide detection probe were used to specifically detect Cl. botulinum type A neurotoxin gene (BoNT/A). After 40 cycles of amplification, detection of a 798 bp amplified DNA fragment was carried out by agarose gel electrophoresis and Southern blot hybridization. This assay was able to detect 12.5 fg of purified target DNA or five bacteria per reaction. The sensitivity in artificially contaminated food samples after an 18 h enrichment step ranges from 10 to 10(3) bacteria per g according to the type of food samples. No cross-reactions were observed with the other Cl. botulinum toxinotypes and other bacteria found routinely in food. This PCR method may provide a suitable and rapid alternative to standard techniques for detection of Cl. botulinum type A in food samples.     

Substrates for protein kinase CK2 in insulin receptor preparations from rat liver membranes: identification of a 210-kDa protein substrate as the dimeric form of endoplasmin

The cytoskeleton is essential for the proper function of many components of secretory and endocytic pathways, and the importance both of microtubule motors (kinesins and dyneins) and of actin motors (myosins) in these pathways is becoming apparent. Recent experiments have improved our understanding of which members of these motor protein families are involved in membrane traffic. Multiple motors are probably involved in the control of the morphology and dynamics of many membranes, and intriguing hints about how these motors are coordinated are appearing.     

Human peroxisome proliferator-activated receptor-gamma2: genetic mapping, identification of a variant in the coding sequence, and exclusion as the gene responsible for lipoatrophic diabetes

Persistent dislocation of the elbow after a fracture of the coronoid process is a difficult problem. We have performed an open reduction with reconstruction of the coronoid by an osteocartilaginous graft from the ipsilateral olecranon for two patients. Both achieved a painless, stable joint with a functional range of movement. The joint surface of the graft has a similar curve to that of the coronoid giving good congruency and stability. The technique is simple and the graft is obtained through the same incision.     

Tumour necrosis factor-alpha as a target of melanocortins in haemorrhagic shock, in the anaesthetized rat

The cytokine tumour necrosis factor-alpha (TNF-alpha) is involved (mostly through the activation of inducible nitric oxide synthase) in the pathogenesis of circulatory shock. On the other hand, melanocortin peptides are potent and effective in reversing haemorrhagic shock, both in animals (rat, dog) and in humans. This prompted us to study the influence of the melanocortin peptide ACTH-(1-24) on the blood levels of TNF-alpha in haemorrhage-shocked rats and on the in vitro production of TNF-alpha by lipopolysaccharide (LPS)-activated macrophages. Plasma levels of TNF-alpha were undetectable before starting bleeding and greatly increased 20 min after bleeding termination in saline-treated rats. In rats treated with ACTH-(1-24) the almost complete restoration of cardiovascular function was associated with markedly reduced levels of TNF-alpha 20 min after bleeding termination. On the other hand, ACTH-(1-24) did not influence TNF-alpha plasma levels in sham-operated, unbled rats. In vitro, ACTH-(1-24) (25-100 nM) dose-dependently reduced the LPS-stimulated production of TNF-alpha by peritoneal macrophages harvested from untreated, unbled rats. These results indicate that inhibition of TNF-alpha overproduction may be an important component of the mechanism of action of melanocortins in reversing haemorrhagic shock.     

Involvement of ovarian kinin-kallikrein system in the pathophysiology of ovarian hyperstimulation syndrome: studies in a rat model

The purpose of the present study was to investigate a possible participation of the kinin-kallikrein system (KKS) in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Symptoms of hyperstimulation were produced in immature female rats using equine chorionic gonadotrophin followed by human chorionic gonadotrophin (HCG). At 48 h after the HCG injection, rats were injected s.c. with 100 microg/kg of HOE140, bradykinin-2 receptor antagonist. Capillary permeability was evaluated using peritoneal Evans blue dye (EB) concentrations 30 min after the i.v. injections. The EB concentrations in the hyperstimulated rats were significantly reduced 4 and 6 h after the HOE140 injection, compared with those injected with the vehicle as a control (4.58+/-0.80 versus 8.22+/-0.87 and 4.32+/-0.74 versus 8.35+/-1.03 microg respectively; P < 0.03), indicating the involvement of kinin in the pathophysiology of OHSS in this model. The administration of 10 IU aprotinin significantly reduced the peritoneal EB concentration when compared with the control (4.13+/-0.53 versus 7.95+/-1.06 microg; P < 0.01), implicating a possible role of kallikrein. Furthermore, pretreatment with RU486 (5 or 10 mg/kg) resulted in a significant reduction of ovarian kinin concentrations 48 h after the HCG injection, compared with the control (1.22+/-0.07 or 1.43+/-0.07 versus 1.94+/-0.10 pg/mg; P < 0.005 and P < 0.05 respectively). Similar results were obtained in the peritoneal EB concentrations. In addition, a significant correlation between the ovarian kinin and peritoneal EB concentrations was observed (P < 0.001, r = 0.539). Thus it was suggested that ovarian KKS plays an intermediary role in the progesterone-induced augmentation of capillary permeability in this experimental model, indicating the involvement of KKS in the pathophysiology of OHSS.     

Bile acids and lipids in isolated rat hepatocytes: content, synthesis, and release, as affected by cholestyramine treatment of the donor rats

Contents of bile acids and lipids, as well as rates of triglyceride synthesis, were determined in isolated hepatocytes from control or cholestyramine-fed rats (denoted below as "control" or "treated" hepatocytes, respectively). During a 3-hr incubation period, total bile acid production was markedly higher in "treated" cells than in "control" cells. With both kinds of cells a marked fall in production rate occurred after the first hour of incubation. Newly produced bile acids appeared in the conjugated form with both kinds of hepatocytes. "Control" cells produced only taurine-conjugated, while "treated" cells made both taurine-conjugated and glycine-conjugated bile acids. However, with exogenous taurine (0.5 mM), the latter cells also produced taurine-conjugated bile acids only. With both kinds of cells, cholic and beta-muricholic acids, but not dihydroxylated bile acids, appeared as newly formed species during the incubation. Addition of dialyzed rat serum to the incubation did not result in a stimulation of bile acid production, with either kind of hepatocytes. "Treated" cells had a slightly higher content of free cholesterol than control cells; contents of other lipids were not different. Fractional release of bile acids and lipids into the medium did not differ between the two kinds of cells. Triglyceride synthesis from added [14C]palmitate (0.5 mM) was 1.8-fold higher in "treated" than in "control" hepatocytes.