Biomedical subjects

S Zhao

Publications and source records attributed to S Zhao.

At least 343 records · Page 19Linked to original sources

PubMed1997

Thromboxane inhibitors attenuate pathological changes in alcoholic liver disease in the rat.

BACKGROUND & AIMS: Thromboxane levels correlate with severity of liver injury in rats given alcohol. The aim of this study was to evaluate the effect of thromboxane inhibitors on pathological changes in experimental alcoholic liver disease. METHODS: Male Wistar rats were given a liquid diet and ethanol intragastrically for 1 month. The thromboxane inhibitors tested were a thromboxane receptor antagonist (TXRA) and a thromboxane synthase inhibitor (TXSI). Pathological changes, liver and plasma thromboxane levels, 6-ketoprostaglandin F1 alpha levels, lipid peroxidation, and messenger RNA levels for tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF) beta were evaluated. RESULTS: Treatment with thromboxane inhibitors prevented necrosis and inflammation. In the TXSI-treated group, fatty liver was also decreased. Ethanol administration led to a 3-4-fold increase in liver thromboxane levels; a reduction in thromboxane levels and lipid peroxidation was seen in the TXSI group. In all treatment groups, TNF-alpha and TGF-beta messenger RNA levels were decreased. CONCLUSIONS: The prevention of necroinflammatory changes in thromboxane-treated groups is related to a decrease in TNF-alpha levels. Inhibition of TGF-beta expression may also prevent fibrosis in ethanol-treated rats.

Animals↗

PubMed1997

Differentiation and transdifferentiation of the retinal pigment epithelium.

The retinal pigment epithelium (RPE) lies between the retina and the choroid of the eye and plays a vital role in ocular metabolism. The RPE develops from the same sheet of neuroepithelium as the retina and the two derivatives become distinguished by different expression patterns of a number of transcription factors during embryonic development. As the RPE layer differentiates it expresses a set of unique molecules, many of which are restricted to certain regions of the cell. PRE cells undergo both a loss of polarity and a loss of expression of many of these cell type-specific molecules when placed in monolayer culture. The RPE of many species, including mammals, can be induced to transdifferentiate by growth factors such as basic fibroblast growth factor. Under the influence of such factors the RPE is triggered to alter expression of a wide array of molecules and to take on a retinal epithelium fate, from which differentiated retinal cell types including rod photoreceptors can be produced.

Animals↗

PubMed1997

Prevalence, correlates, and course of minor depression and major depression in the National Comorbidity Survey.

Data from the National Comorbidity Survey are used to study the lifetime prevalences, correlates, course and impairments associated with minor depression (mD), major depression 5-6 symptoms (MD 5-6), and major depression with seven or more symptoms (MD 7-9) in an effort to determine whether mD is on a continuum with MD. There is a monotonic increase in average number of episodes, average length of longest episode, impairment, comorbidity, and parental history of psychiatric disorders as we go from mD to Md 5-6 to MD 7-9. In most of these cases, though, the differences between mD and MD 5-6 are no longer than the differences between MD 5-6 and MD 7-9, arguing for continuity between mD and MD. Coupled with the finding from earlier studies that subclinical depression is a significant risk factor for major depression, these results argue that minor depression is a variant of depressive disorder that should be considered seriously both as a target for preventive intervention and for treatment. The paper closes with suggestions regarding the analysis of mD subtypes in future longitudinal studies.

Adolescent↗

PubMed1997

Comparison between qualitative and quantitative wall motion analyses using dipyridamole stress breath-hold cine magnetic resonance imaging in patients with severe coronary artery stenosis.

Breath-hold cine magnetic resonance imaging (MRI) at rest and during dipyridamole infusion was used to study wall motion abnormalities in patients with severe coronary artery stenosis proven by coronary angiography. Sixteen patients without myocardial infarction but at least one major coronary artery with > or = 70% diameter narrowing were included. Qualitative "visual" assessment of wall motion, as well as quantitative measurement "wall thickening changes (%)" were compared using receiver operating characteristic curve analysis. 201Tl-single-photon emission computed tomography (SPECT) was also studied for comparison. Using qualitative analysis, coronary artery disease detection rate was comparable when assessing wall motion abnormalities with dipyridamole-MRI (79%) and with dipyridamole-induced perfusion defects with 201-thallium-SPECT (75%). Furthermore, sensitivity and specificity for identification of all diseased coronary territories were comparable for both imaging modalities (sensitivity of dipyridamole-MRI and 201thallium-SPECT, 80% vs. 69%; specificity, 75% vs. 80%). The quantitative method has a substantially higher sensitivity than the qualitative method in identifying all diseased territories (Az = 0.81, p < 0.01 vs. Az = 0.55 and 0.59). In addition, we demonstrated that the quantitative method had higher performance than the qualitative one in identifying the diseased vessels territories related to 1-vessel, 2-vessel, and each of individual coronary artery stenoses.

Aged↗

PubMed1997

The epidemiology of DSM-III-R bipolar I disorder in a general population survey.

BACKGROUND: Data are presented on the general population epidemiology of DSM-III-R bipolar I disorder in the United States. METHODS: Data come from the US National Comorbidity Survey (NCS), a general population survey of DSM-III-R disorders. A modified version of the Composite International Diagnostic Interview was used to make diagnoses. RESULTS: A small (N = 59) clinical reappraisal study showed that the only manic symptom profile that could validly be assessed with the CIDI is characterized by euphoria, grandiosity and the ability to maintain energy without sleep, which described approximately half of all clinically validated bipolar I cases in the NCS. Further analysis focused on this symptom profile, which involved N = 29 cases in the total sample. Lifetime prevalence was estimated to be 0.4% and 12-month prevalence only slightly lower. Caseness was negatively related to income, education and age, positively related to urbanicity, and elevated among the previously married, never married and non-whites. All cases reported at least one other NCS/DSM-III-R disorder and 59.3% reported that their episode of bipolar disorder (either mania or depression) occurred at a later age than at least one other NCS/DSM-III-R disorder. Although 93.2% of lifetime cases reported some lifetime treatment, only 44.7% of recent cases were in treatment. CONCLUSIONS: The type of bipolar disorder examined here is highly chronic, co-morbid and impairing. Increased efforts are required to attract current cases into appropriate treatment. Methodological research is needed to develop more accurate measures of other bipolar symptom profiles for use in general population epidemiological studies.

Age of Onset↗

PubMed1997

Cellular pharmacology of mitoxantrone in p-glycoprotein-positive and -negative human myeloid leukemic cell lines.

Previous reports suggest that resistance to mitoxantrone in different tumor cell lines is unrelated to the overexpression of p-glycoprotein. In order to determine the role of p-glycoprotein in the cellular pharmacology of mitoxantrone flow cytometry and confocal microscopy were used to study two human myeloid leukemia cell lines selected for resistance to mitoxantrone (HL-60MX2) and doxorubicin (HL-60DOX). To optimize the detection of intracellular mitoxantrone, we determined the maximum excitation (607 nm) and emission (684 nm) wavelength by fluorescence spectroscopy. The modified flow cytometric conditions using 568.2 nm laser emission for excitation and a 620 nm long pass filter for fluorescence collection resulted in a 1-log increase in sensitivity, compared with standard 488-nm laser excitation. Uptake and retention of mitoxantrone in the presence of verapamil, a calcium channel blocker known to inhibit p-glycoprotein, were analyzed. Our results showed no change in uptake and retention of the drug in p-glycoprotein-negative mitoxantrone-resistant HL-60MX2 cells and in its sensitive parental line, HL-60s. In contrast, 3.1- and 2.4-fold increases were found in uptake and retention of mitoxantrone in p-glycoprotein-positive cells (HL-60DOX) incubated with verapamil. Confocal microscopy of intracellular drug distribution demonstrated reduced nuclear uptake, which could be reversed by verapamil, in HL-60DOX. A characteristic punctate pattern was observed for the intracytoplasmic drug distribution in HL-60DOX and HL-60MX2 cells and was partially modified by the presence of verapamil in HL-60DOX cells. Verapamil increased cytotoxicity of mitoxantrone two-fold in HL-60DOX cells, 1.4-fold in HL-60MX2, and had no effect in HL-60s. Our study demonstrates that the cellular pharmacology of mitoxantrone is affected by p-glycoprotein and can be reversed at least in part by verapamil. Other mechanisms of resistance however, seem to play a determinant role in the modulation of mitoxantrone cytotoxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

2-Chlorodeoxyadenosine therapy for idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (HES) is a rare disease with no established effective therapy. It has been reported that interleukin-5 (IL-5) produced by helper T cells plays a major role in the proliferation of eosinophils. The nucleotide analogue 2-chlorodeoxyadenosine (2-CdA), which induces excellent clinical responses in hairy cell leukemia, is known to suppress helper T cells; therefore, we used 2-CdA, alone or in combination with cytarabine, to treat patients with idiopathic HES. 2-CdA alone and combined with cytarabine resulted in a rapid and sustained decrease in circulating eosinophils in two patients with idiopathic HES that was refractory to steroids, hydroxyurea and cytarabine. The efficacy of 2-CdA alone and combined with cytarabine exceeded by far that of cytarabine alone. However, reverse transcription-polymerase chain reaction (RT-PCR) did not show production of IL-5 or granulocyte-macrophage colony-stimulating factor mRNA in T cells as previously reported, and multiple cytokine receptors were found on eosinophils in idiopathic HES, suggesting that IL-5 may not be the sole cytokine involved in the regulation of idiopathic HES. The clinical efficacy of 2-CdA in idiopathic HES needs to be established on a large group of patients.

Adult↗

PubMed1997

Activity of TNF-related apoptosis-inducing ligand (TRAIL) in haematological malignancies.

T-cell cytotoxicity is primarily mediated by two cell surface proteins, Fas ligand (FasL) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and intracellular perforin and granzyme granules. FasL-deficient and perforin-deficient T lymphocytes maintain cytotoxicity but fail to induce graft-versus-host disease (GVHD) when transplanted into mice. suggesting that GVHD and graft-versus-tumour (GVT) effects can be dissociated, and that TRAIL is not involved in the pathogenesis of GVHD. Because TRAIL could mediate a favourable GVT effect it became important to study the spectrum of its activity and to investigate factors that can dissociate its expression from FasL. TRAIL induced apoptosis in 11/41 (27%) tumour specimens of haematological origin compared to 16/41 (39%) induced by FasL. Although eight specimens were sensitive to both FasL and TRAIL, no synergism was observed between these two ligands. TRAIL induced apoptosis in a dose and time dependent manner with an ED50 of 0.5 microg/ml and EDmax of 1 microg/ml. TRAIL activity was not reduced by the over-expression of the multidrug resistant (MDR) protein, and was not enhanced by 9-cis retinoic acid (RA), which can down-regulate bcl-2 protein. Both ligands were simultaneously up-regulated in normal peripheral blood lymphocytes in response to IL-2, IL-15 and anti-CD3 antibody, whereas IL-10 had no effect. Together, our data show that (1) TRAIL can mediate cell death in a variety of human haematological malignancies, (2) resistance to TRAIL is not mediated by MDR protein, (3) the lack of synergy between TRAIL and FasL suggests that either one is sufficient to mediate T-cell cytotoxicity, and (4) within the panel of cytokines tested, the expression of TRAIL and FasL could not be dissociated.

Apoptosis↗

PubMed1997

Association of brain protein phosphatase 1 with cytoskeletal targeting/regulatory subunits.

Protein phosphatase 1 catalytic subunit (PP1C) is highly enriched in isolated rat postsynaptic densities. Gel overlay analyses using digoxigenin (DIG)-labeled PP1C revealed four major rat brain PP1C-binding proteins (PP1bps) with molecular masses of approximately 216, 175, 134, and 75 kDa, which were (1) more abundant in brain than other rat tissues; (2) differentially expressed in microdissected brain regions; and (3) enriched in isolated cortex postsynaptic densities. PP1bp175, PP1bp134, PP1bp75, and PP1C were partially released from forebrain particulate extracts by incubation at low ionic strength, which destabilizes the actin cytoskeleton. Size-exclusion chromatography of solubilized extracts separated two main PP1 activities (approximately 600 and approximately 100 kDa). PP1bps and PP1C gamma1 were enriched in the approximately 600-kDa peak, but PP1C beta was enriched in the approximately 100-kDa peak. Furthermore, PP1bp175 and PP1bp134 exhibited lower binding of recombinant DIG-PP1C beta than recombinant DIG-PP1C gamma1 or DIG-PP1C alpha. Solubilized PP1bp175 and PP1bp134 interact with PP1C under native conditions, because they both (1) coeluted from size-exclusion and ion-exchange columns; (2) bound to microcystin-LR-Sepharose; and (3) coprecipitated using PP1C antibodies. Trypsinolysis of the approximately 600-kDa form of PP1 increased phosphorylase a phosphatase activity approximately fourfold, suggesting that interaction of PP1C with these PP1bps modulates its activity. Thus, brain PP1 activity is likely targeted to the cytoskeleton, including postsynaptic densities, by isoform-selective binding of PP1C to these targeting/regulatory subunits, contributing to the specificity of its physiological roles.

Animals↗

PubMed1997

A multiplex PCR for identifying Shiga-like toxin-producing Escherichia coli O157:H7.

A multiplex PCR assay specifically detecting Escherichia coli O157:H7 was developed by employing primers amplifying a DNA sequence upstream of E. coli O157:H7 eaeA gene and genes encoding Shiga-like toxins (SLT) I and II. Analysis of 151 bacterial strains revealed that all E. coli O157:H7 strains were identified simultaneously with the SLT types and could be distinguished from E. coli O55:H7 and E. coli O55:NM, and other non-O157 SLT-producing E. coli strains. Primer design, reaction composition (in particular, primer quantity and ratios), and amplification profile were most important in development of this multiplex PCR. This assay can serve not only as a confirmation test but also potentially can be applied to detect the pathogen in food.

Adhesins, Bacterial↗

PubMed1997

Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat.

BACKGROUND & AIMS: Inflammatory stimuli and lipid peroxidation up-regulate cyclooxygenase (COX)-2. This study evaluated the relationship between inflammatory mediators, COX expression, and pathological changes in experimental alcoholic liver disease. METHODS: Rats (5 per group) were fed ethanol and a diet containing saturated fat, corn oil, or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In the first set of experiments, whole livers were analyzed. In the second set of experiments, Kupffer cells, endothelial cells, and hepatocytes were isolated from rats in each group. Pathological analyses and measurements of lipid peroxidation, tumor necrosis factor (TNF)-alpha, COX-1 and COX-2 messenger RNA (mRNA), endotoxin, and liver and plasma thromboxane were performed. RESULTS: Increased expression of COX-2 mRNA was detected in the livers of rats showing necroinflammatory changes. The Kupffer cell was the cell primarily responsible for the increase in COX-2 mRNA level. Increased expression of COX-2 was associated with increased levels of endotoxin, TNF-alpha mRNA, lipid peroxidation, and synthesis of thromboxane. COX-1 mRNA was decreased in Kupffer cells in rats with the most severe liver injury. CONCLUSIONS: Up-regulation of COX-2 in alcoholic liver injury occurred in the presence of proinflammatory stimuli and resulted in increased synthesis of inflammatory and vasoactive eicosanoids. Down-regulation of COX-1 may result in decreased synthesis of cytoprotective eicosanoids and additionally exacerbate liver injury.

Animals↗

PubMed1997

Neurotization of motor nerves innervating the lower extremity by utilizing the lower intercostal nerves.

An animal model in the rat was developed to study the reinnervation of ventral roots contributing to lower-extremity nerves by use of intercostal nerves. Intercostal nerves and distal cauda equina roots were anastomosed, using a collagen tube and microsurgical technique. Most experimental animals could lift their previously paralyzed legs and could walk with a severe limp by 9 months postoperatively. Recordings of nerve action potentials (NAPs) and muscle action potentials (MAPs) indicated that the intercostal and sciatic nerves had some functional connections. Histologic analysis 12 months after repair demonstrated axonal regeneration extending from the intercostal nerves to and down lumbar ventral roots. Most of the regenerated fibers were moderately well-myelinated. Connections between the neurons of the anterior horn cells in the lower thoracic spinal cord and the reinnervated sciatic nerve were confirmed by retrograde tracer, using fast blue.

Action Potentials↗

PubMed1997

A new nuclear gene for insect phylogenetics: dopa decarboxylase is informative of relationships within Heliothinae (Lepidoptera: Noctuidae).

The lack of a readily accessible roster of nuclear genes informative at various taxonomic levels is a bottleneck for molecular systematics. In this report, we describe the first phylogenetic application of the sequence that encodes the enzyme dopa decarboxylase (DDC). For 14 test species within the noctuid moth subfamily Heliothinae that represent the previously best-supported groupings, a 690-bp fragment of DDC resolved relationships that are largely concordant with prior evidence from elongation factor-1 alpha (EF-1 alpha), morphology, and allozymes. Although both synonymous and nonsynonymous changes occur in DDC substantially more rapidly than they do in EF-1 alpha, DDC divergences within Heliothinae are below saturation at all codon positions. Analysis of DDC and EF-1 alpha in combination resulted in increased bootstrap support for several groupings. As a first estimate of previously unresolved relationships, DDC sequences were analyzed from 16 additional heliothines, for a total of 30 heliothine species plus outgroups. Previous relationships based on DDC were generally stable with increased taxon sampling, although a two- to eightfold downweighting of codon position 3 was required for complete concordance with the 14-species result. The weighted strict consensus trees were largely resolved and were congruent with most although not all previous hypotheses based on either morphology or EF-1 alpha. The proposed phylogeny suggests that the major agricultural pest heliothines belong to a single clade, characterized by polyphagy and associated life history traits, within this largely host-specific moth subfamily. DDC holds much promise for phylogenetic analysis of Tertiary-age animal groups.

Animals↗

PubMed1997

Detection of altered adhesion molecule expression in experimental tumors by a radiolabeled monoclonal antibody.

Adhesion molecules play a major role in the processes of invasion and metastasis of malignant tumors. Their expression within tumors has been reported to be quantitatively and qualitatively altered according to the invasiveness and metastatic potential of the tumor. The present study tested whether the intratumoral expression of integrin alpha 3 can be detected by a radiolabeled monoclonal antibody. The in vitro binding study with four different human cancer cells showed that radioiodinated GA17 antibody recognizing integrin alpha 3 bound specifically to these cells to varying degrees, according to the antigen density on each cell. The biodistribution study with 125I- and 111In-labeled antibodies showed specific localization of radiolabeled GA17 to the xenografts. However, the in vivo tumor localization was not proportional to the antigen density calculated in vitro, and antibody metabolism varied among the tumors, as was also confirmed by in vitro radionuclide retention assay. The intratumoral distribution of radioactivities varied reflecting the antigen expression within the tumor. These results indicate that 1) integrin alpha 3 was expressed in various kinds of tumors and could be localized by the radiolabeled antibody, and 2) the expression of integrin alpha 3 and the metabolism of the radiolabeled antibody after binding to the antigen within the tumor were variable among the tumors, which affected the radionuclide distribution characteristics. The expression of adhesion molecules within these tumors was noninvasively detected by a radiolabeled antibody. It may be possible to use integrin alpha 3, when it is overexpressed, as a target of therapy with antibodies radiolabeled with alpha or beta emitters.

Animals↗

PubMed1997

Human blue-light photoreceptor hCRY2 specifically interacts with protein serine/threonine phosphatase 5 and modulates its activity.

Photolyase/blue-light photoreceptor family of proteins includes cyclobutane pyrimidine dimer photolyase, (6-4) photolyase and blue-light photoreceptors that were recently discovered in Arabidopsis thaliana, Sinapis alba and Chlamydomonas reinhardtii. Recently, we identified two human genes, hCRY1 and hCRY2, belonging to this family. The proteins encoded by these genes have no DNA repair activity and therefore were hypothesized to function in human blue-light response reactions. To identify downstream targets for these putative blue-light photoreceptors we searched for interacting proteins by the yeast two-hybrid method. We found that the tetratricopeptide repeat protein 1, Tpr1, and the protein serine/threonine phosphatase 5 (PP5) that contains the TPR motif specifically interacted with hCRY2. The effect of the hCRY2-PP5 interaction on the protein phosphatase activity was investigated. We found that hCRY2, but not the highly homologous (6-4) photolyase, inhibits the phosphatase activity of PP5. This inhibition may be on the pathway of blue-light signal transduction reaction in humans.

Animals↗

PubMed1997

Rifampicin carrying polyhydroxybutyrate microspheres as a potential chemoembolization agent.

In this study, we attempted to prepare microspheres from a microbial biodegradable polyester, i.e. polyhydroxybutyrate (PHB) as a potential chemoembolization agent. The drug loaded PHB microspheres were prepared by a solvent evaporation technique, in which methylene chloride, distilled water, and polyvinyl alcohol were utilized as the solvent, dispersion medium, and emulsifier, respectively. Microspheres were obtained within a size range of 5-100 microns by changing the initial polymer/solvent ratio, emulsifier concentration, stirring rate, and initial drug concentration. It was possible to obtain PHB with very narrow size distributions by applying gravity field-flow fractionation technique. Very high drug loadings of up to 407.6 mg rifampicin/g PHB were achieved. Drug release rates were very rapid. Almost 90% of the drug loaded was released in about 24 h. Both the size and drug content of PHB microspheres were found to be effective in controlling the drug release from these microspheres.

Antibiotics, Antitubercular↗

PubMed1997

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia.

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Evidence that systemic relaxin promotes moderate water consumption during late pregnancy in rats.

The protein hormone relaxin is secreted by the ovaries throughtout the second half of the 23 day pregnancy in the rat. We recently reported that neutralization of endogenous relaxin with monoclonal antibodies for rat relaxin decreases water consumption during the daily light period during the second half of pregnancy in rats. The apparent effects of relaxin on water consumption, however, were extremely modest. One explanation for the failure to observe a greater relaxin-dependent effect on water consumption is failure of the monoclonal antibody for rat relaxin to neutralize all circulating relaxin. A second explanation is that circulating relaxin has only slight effects on water consumption. This investigation was conducted with an experimental model in which circulating relaxin was removed in order to re-examine the effects of relaxin on water consumption during the daily light period in late pregnancy in rats. On day 9 (D9) of pregnancy, before the presence of relaxin (R) in the circulation, primiparious pregnant rats were ovariectomized (O) or sham ovariectomized (C). Throughout the remainder of pregnancy, rats were treated with combinations of either progesterone (P) and estrogen (E, group OPE) or progesterone, estrogen and porcine relaxin (group OPER) in doses that restore physiological parameters to values similar to those that occur during the second half of pregnancy in intact rats. Progesterone and estrogen were administered by Silastic tubing implants and porcine relaxin was administered via miniature osmotic pump. Sham-ovariectomized animals received either the hormone vehicles (group SC) or no implants (group IC). Water consumption was measured daily from D4 to D20 at both 0700 and 2100 h which was when the lights went on and off respectively. Water consumption increased as pregnancy continued from D10 to D20 during the daily 10 h dark periods (P < 0.01), but not during the 14 h light periods for all four groups. Daily water consumed by rats in group OPE was significantly lower (P < 0.05) than that consumed by shamovariectomized rats from D17 to D20 and lower than that consumed by rats in group OPER on D20. During the dark period there was no difference in water consumption among groups. During the light period, however, group OPE consumed significantly less water (P < 0.05) than group C from D18 to D22. Moreover, there was a consistent tendency (P < 0.13) for the water consumption to be greater in rats in group OPER than in those in the relaxin-deficient group OPE during the daily light period from D11 to D20 of pregnancy. We conclude that the increase in water consumption that occurs during the daily dark periods during the second half of pregnancy is not attributable to circulating relaxin. Circulating relaxin promotes only modest increases in water consumption during the daily light periods during late pregnancy in the rat.

Animals↗