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1.
J Psychiatr Ment Health Nurs ; 25(4): 217-227, 2018 May.
Article in English | MEDLINE | ID: mdl-29283493

ABSTRACT

WHAT IS KNOWN ON THE SUBJECT?: The psychometrics of the CUB measure have been tested within an inpatient psychiatric setting. Results show that the CUB has two factors that reflect patients' approach and avoidance of dimensions of the treatment milieu, and that an increase of approach and decrease of avoidance are correlated with discharge. No empirical research has examined the validity of the CUB in a day hospital programme. WHAT THIS ARTICLE ADDS TO EXISTING KNOWLEDGE?: This study was the first to address the validity of this questionnaire within a psychiatric day hospital setting. This now allows other mental health service providers to use this questionnaire following administration of patient engagement interventions (such as behavioural activation), which are routinely used within this type of a setting. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Our results can enable healthcare providers to employ an effective and psychometrically validated tool in a day hospital setting to measure treatment outcomes and provide reflections of patients' approach behaviours and avoidance behaviours. ABSTRACT: Introduction We evaluated the Checklist of Unit Behaviours (CUBs) questionnaire in a novel mental health setting: a day hospital within a large acute care general hospital. No empirical evidence exists, as of yet, to look at the validity of this measure in this type of a treatment setting. The CUB measures two factors, avoidance or approach, of the patients' engagement with the treatment milieu within the previous 24 hr. Aim A confirmatory factor analysis (CFA) was conducted to validate the CUB's original two factor structure in an outpatient day programme. Methods Psychiatric outpatients (n = 163) completed the CUB daily while participating in a day hospital programme in Toronto, Canada. Results A CFA was used to confirm the CUB factors but resulted in a poor fitting model for our sample, χ2 (103) = 278.59, p < .001, CFI = 0.80, RMSEA = 0.10, SRMR = 0.10. Questions 5, 8 and 10 had higher loadings on a third factor revealed through exploratory factor analysis. We believe this factor, "Group Engagement," reflects the construct of group-related issues. Discussion The CUB was a practical and useful tool in our psychiatric day hospital setting at a large acute care general hospital. Implications for practice Our analysis identified group engagement, a critical variable in day programmes, as patients have autonomy regarding staying or leaving the programme.


Subject(s)
Checklist/standards , Mental Disorders/psychology , Outpatient Clinics, Hospital , Outpatients/psychology , Patient Acceptance of Health Care/psychology , Psychometrics/standards , Adult , Aged , Canada , Female , Humans , Male , Middle Aged , Surveys and Questionnaires/standards , Young Adult
2.
Acta Psychiatr Scand ; 121(6): 480-4, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19958307

ABSTRACT

OBJECTIVE: In order to evaluate the presence of treatment emergent suicidal ideation (SI), it becomes necessary to identify those patients with SI at the onset of treatment. The purpose of this report is to identify sociodemographic and clinical features that are associated with SI in major depressive disorder (MDD) patients prior to treatment with a selective serotonin reuptake inhibitor. METHOD: This multisite study enrolled 265 out-patients with non-psychotic MDD. Sociodemographic and clinical features of participants with and without SI were compared post hoc. RESULTS: Social phobia, bulimia nervosa, number of past depressive episodes, and race were independently associated with SI by one or more SI measure. CONCLUSION: Concurrent social phobia and bulimia nervosa may be potential risk factors for SI in patients with non-psychotic MDD. Additionally, patients with more than one past depressive episode may also be at increased risk of SI.


Subject(s)
Bulimia Nervosa/complications , Depressive Disorder, Major , Phobic Disorders/complications , Selective Serotonin Reuptake Inhibitors , Suicide, Attempted , Adult , Aged , Ambulatory Care Facilities , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Bulimia Nervosa/diagnosis , Comparative Effectiveness Research , Demography , Depressive Disorder, Major/complications , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/psychology , Diagnostic and Statistical Manual of Mental Disorders , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Phobic Disorders/diagnosis , Psychiatric Status Rating Scales , Risk Factors , Secondary Prevention , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/adverse effects , Suicidal Ideation , Suicide, Attempted/prevention & control , Suicide, Attempted/psychology , United States , Young Adult
3.
Psychol Med ; 40(6): 955-65, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19785919

ABSTRACT

BACKGROUND: Attitudes and expectations about treatment have been associated with symptomatic outcomes, adherence and utilization in patients with psychiatric disorders. No measure of patients' anticipated benefits of treatment on domains of everyday functioning has previously been available. METHOD: The Anticipated Benefits of Care (ABC) is a new, 10-item questionnaire used to measure patient expectations about the impact of treatment on domains of everyday functioning. The ABC was collected at baseline in adult out-patients with major depressive disorder (MDD) (n=528), bipolar disorder (n=395) and schizophrenia (n=447) in the Texas Medication Algorithm Project (TMAP). Psychometric properties of the ABC were assessed, and the association of ABC scores with treatment response at 3 months was evaluated. RESULTS: Evaluation of the ABC's internal consistency yielded Cronbach's alpha of 0.90-0.92 for patients across disorders. Factor analysis showed that the ABC was unidimensional for all patients and for patients with each disorder. For patients with MDD, lower anticipated benefits of treatment was associated with less symptom improvement and lower odds of treatment response [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.87, p=0.0011]. There was no association between ABC and symptom improvement or treatment response for patients with bipolar disorder or schizophrenia, possibly because these patients had modest benefits with treatment. CONCLUSIONS: The ABC is the first self-report that measures patient expectations about the benefits of treatment on everyday functioning, filling an important gap in available assessments of attitudes and expectations about treatment. The ABC is simple, easy to use, and has acceptable psychometric properties for use in research or clinical settings.


Subject(s)
Bipolar Disorder/drug therapy , Depressive Disorder, Major/drug therapy , Goals , Psychotropic Drugs/therapeutic use , Schizophrenia/drug therapy , Schizophrenic Psychology , Surveys and Questionnaires , Adaptation, Psychological , Adult , Algorithms , Bipolar Disorder/diagnosis , Bipolar Disorder/economics , Bipolar Disorder/psychology , Brief Psychiatric Rating Scale/statistics & numerical data , Combined Modality Therapy , Cost-Benefit Analysis , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/economics , Depressive Disorder, Major/psychology , Female , Humans , Male , Middle Aged , Personality Inventory/statistics & numerical data , Psychometrics , Psychotropic Drugs/economics , Schizophrenia/diagnosis , Schizophrenia/economics , Social Adjustment , Treatment Outcome
4.
J Biol Chem ; 276(26): 23492-8, 2001 Jun 29.
Article in English | MEDLINE | ID: mdl-11313362

ABSTRACT

A wide array of drugs, xenobiotics, and endogenous compounds undergo detoxification by conjugation with glucuronic acid in the liver via the action of UDP-glucuronosyltransferases. The mechanism whereby glucuronides, generated by this enzyme system in the lumen of the endoplasmic reticulum (ER), are exported to the cytosol prior to excretion is unknown. We examined this process in purified rat liver microsomes using a rapid filtration technique and [(3)H]estradiol-17beta-d-glucuronide ([(3)H]E(2)17betaG) as model substrate. Time-dependent uptake of intact [(3)H]E(2)17betaG was observed and shrinkage of ER vesicles by raffinose lowered the steady-state level of [(3)H]E(2)17betaG accumulation. In addition, rapid efflux of [(3)H]E(2)17betaG from rat liver microsomal vesicles suggested that the transport process is bidirectional. Microsomal uptake was saturable with an apparent K(m) and V(max) of 3.29 +/- 0.58 microm and 0.19 +/- 0.02 nmol.min(-1).mg protein(-1), respectively. Transport of [(3)H]E(2)17betaG was inhibited by the anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and probenecid. Specificity of the transport process was investigated by studying the cis-inhibitory effect of anionic metabolites, as well as substrates of the plasma membrane multidrug resistance-associated proteins on the uptake of [(3)H]E(2)17betaG. Collectively, these data are indicative of a novel multifunctional and bidirectional protein carrier for E(2)17betaG and other anionic compounds in the hepatic ER. This intracellular membrane transporter may contribute to the phenomenon of multidrug resistance.


Subject(s)
Carrier Proteins/metabolism , Estradiol/metabolism , Microsomes, Liver/metabolism , Animals , Biological Transport/drug effects , Culture Media , Estradiol/analogs & derivatives , Intracellular Membranes/metabolism , Ion Transport , Kinetics , Male , Microsomes, Liver/drug effects , Osmolar Concentration , Rats , Rats, Sprague-Dawley , Stilbenes/pharmacology , Substrate Specificity , Temperature , Transport Vesicles/metabolism
6.
Am J Physiol ; 275(4): G717-22, 1998 10.
Article in English | MEDLINE | ID: mdl-9756502

ABSTRACT

Gluconeogenesis and glycogenolysis are essential hepatic functions required for glucose homeostasis. During the initial phase of hepatic regeneration, the immediate-early genes (IEG) are rapidly expressed, and the IEG RL-1 encodes for glucose-6-phosphatase (G-6-Pase). G-6-Pase is a microsomal enzyme essential for gluconeogenesis and glycogenolysis. This study employs a partial-hepatectomy model to examine the expression and activity of G-6-Pase. After partial hepatectomy, rat hepatic G-6-Pase gene expression is transcriptionally regulated, and mRNA levels are increased approximately 30-fold. However, in contrast to this rapid gene induction, microsomal enzyme activity is unchanged after partial hepatectomy. Western blotting demonstrates that microsomal G-6-Pase protein expression is also unchanged after partial hepatectomy, and similar results are also noted in whole liver homogenate. Thus, despite marked induction in gene expression of the IEG G-6-Pase after partial hepatectomy, protein expression and enzyme activity remain unchanged. These data indicate that, although this hepatocyte IEG is transcriptionally regulated, the physiologically important level of regulation is posttranscriptional. This highlights the importance of correlating gene expression of IEG with protein expression and physiological function.


Subject(s)
Gene Expression Regulation, Enzymologic , Glucose-6-Phosphatase/genetics , Liver Regeneration/physiology , Liver/enzymology , Microsomes, Liver/enzymology , Transcription, Genetic , Animals , Cell Nucleus/metabolism , Glucose-6-Phosphatase/biosynthesis , Hepatectomy , Liver/physiology , Male , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Time Factors , Transcriptional Activation
7.
J Consult Clin Psychol ; 66(2): 377-84, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9583341

ABSTRACT

This study presents 2-year follow-up data of a comparison between complete cognitive-behavioral therapy for depression (CT) and its 2 major components: behavioral activation and behavioral activation with automatic thought modification. Data are reported on 137 participants who were randomly assigned to 1 of these 3 treatments for up to 20 sessions with experienced cognitive-behavioral therapists. Long-term effects of the therapy were evaluated through relapse rates, number of asymptomatic or minimally symptomatic weeks, and survival times at 6-, 12-, 18-, and 24-month follow-ups. CT was no more effective than its components in preventing relapse. Both clinical and theoretical implications of these findings are discussed.


Subject(s)
Cognitive Behavioral Therapy/methods , Depressive Disorder/therapy , Adult , Depressive Disorder/psychology , Female , Follow-Up Studies , Humans , Internal-External Control , Male , Personality Assessment , Recurrence , Thinking
9.
Am J Physiol ; 273(3 Pt 1): G621-7, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9316464

ABSTRACT

Bile formation is an essential liver-specific function, and the hepatic regeneration that occurs in response to hepatocellular injury is often associated with cholestasis. We have employed a partial hepatectomy model to examine the effect of hepatic regeneration on tissue-specific bile salt transporters and on Na(+)-K(+)-adenosinetriphosphatase (ATPase). Liver-specific sodium-dependent taurocholate uptake by basolateral plasma membrane vesicles was undetectable 24 h after hepatectomy. Basolateral membrane protein expression of the sodium-taurocholate cotransporter and gene expression of Ntcp were decreased by > 90% 24 h after partial hepatectomy. In vitro transcription assays demonstrated that Ntcp gene transcription was also markedly reduced. In contrast, hepatic Na(+)-K(+)-ATPase activity, protein expression, and gene expression were unaffected by partial hepatectomy. Similarly, protein and gene expression of the ectoATPase, a putative canalicular bile salt transporter, and canalicular ATP-dependent taurocholate uptake remained unchanged. Partial hepatectomy results in a marked reduction in the gene transcription and expression of the liver-specific Ntcp, as well as a decrease in protein expression and loss of transport activity. These changes provide a potential mechanism for the decrease in hepatocellular bile salt transport that is associated with hepatic regeneration.


Subject(s)
Adenosine Triphosphatases/biosynthesis , Carrier Proteins/biosynthesis , Liver Regeneration , Liver/physiology , Organic Anion Transporters, Sodium-Dependent , Sodium-Potassium-Exchanging ATPase/biosynthesis , Symporters , Taurocholic Acid/metabolism , Transcription, Genetic , Animals , Cell Membrane/metabolism , DNA Primers , DNA Probes , Kinetics , Male , Polymerase Chain Reaction , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley
10.
Nature ; 388(6641): 482-8, 1997 Jul 31.
Article in English | MEDLINE | ID: mdl-9242408

ABSTRACT

Metal ions are essential cofactors for a wealth of biological processes, including oxidative phosphorylation, gene regulation and free-radical homeostasis. Failure to maintain appropriate levels of metal ions in humans is a feature of hereditary haemochromatosis, disorders of metal-ion deficiency, and certain neurodegenerative diseases. Despite their pivotal physiological roles, however, there is no molecular information on how metal ions are actively absorbed by mammalian cells. We have now identified a new metal-ion transporter in the rat, DCT1, which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+. DCT1 mediates active transport that is proton-coupled and depends on the cell membrane potential. It is a 561-amino-acid protein with 12 putative membrane-spanning domains and is ubiquitously expressed, most notably in the proximal duodenum. DCT1 is upregulated by dietary iron deficiency, and may represent a key mediator of intestinal iron absorption. DCT1 is a member of the 'natural-resistance-associated macrophage protein' (Nramp) family and thus its properties provide insight into how these proteins confer resistance to pathogens.


Subject(s)
Carrier Proteins/metabolism , Cation Transport Proteins , Iron-Binding Proteins , Membrane Proteins/metabolism , Metals/metabolism , Amino Acid Sequence , Animals , Carrier Proteins/genetics , Cations, Divalent , Cells, Cultured , Cloning, Molecular , Humans , Iron/metabolism , Iron Deficiencies , Membrane Potentials , Membrane Proteins/genetics , Molecular Sequence Data , Oocytes/metabolism , Organ Specificity , RNA, Messenger/metabolism , Rats , Sequence Homology, Amino Acid , Xenopus
11.
Psychiatr Clin North Am ; 20(2): 337-52, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9196918

ABSTRACT

Domestic violence is a serious public health concern in the United States. Despite the serious and often tragically fatal consequences of spousal abuse, we have very little understanding about the root causes of domestic violence. We know even less about providing effective treatments and prevention. In this article, we have discussed some of the more promising individual difference variables that discriminate between violent and nonviolent men. We also have addressed some of the growing research on how violent couples are different from nonviolent ones. Unfortunately, methodologic limitations hamper us from being able to discuss definitive risk factors or predictive variables, but we can speak of factors associated with domestic violence. We also have discussed the importance of attending to important differences among violent men and violent couples. The complexity of battering behavior and battering relationships necessarily points researchers and clinicians toward multifaceted research designs and treatment models. The tragedy of domestic violence demands that science continues to address these crucial unanswered questions.


Subject(s)
Domestic Violence , Affect , Alcoholism , Anger , Depression/psychology , Female , Hostility , Humans , Interpersonal Relations , Male , Personality Disorders/psychology
13.
Hepatology ; 24(5): 979-86, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8903363

ABSTRACT

Chronic viral hepatitis frequently goes undetected until cirrhosis develops. Although the effect of interferon on the natural history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in asymptomatic persons is unknown, treatment may modify the course of the infection, producing cures in some. In September 1992, screening for HBV and HCV was offered in 40 centers throughout the United States. Demographic features, potential risk factors, and symptoms were studied. Blood samples were obtained for the determination of serum alanine aminotransferase levels and for markers of HBV and HCV infection. Thirteen thousand nine hundred ninety seven subjects were screened. The prevalence of infection with HBV or HCV was 24.8% (HBV 17.8%; HCV 7.0%; and both 2.8%). Hepatitis B and C disease was present in 0.7% and 4.4% of the population, respectively. Risk factors for HBV and HCV infection were similar in: blood transfusions, hemodialysis, IV drug use, and sex with an IV drug user. For HBV infection, sex with multiple partners, increasing age, and birth in South East Asia or Africa were additional risk factors. The cost to find a case of HCV infection is less than the costs for finding many other treatable diseases. Screening for HBV, though more costly, is reasonably efficient, and simultaneous screening for HBV and HCV provides greater efficiency. It is practical to consider screening for HBV and HCV in the United States, particularly if any risk factor is present. Improved treatment strategies will make screening even more cost effective.


Subject(s)
Hepatitis B/epidemiology , Hepatitis C/epidemiology , Adult , Age Factors , Aged , Cost-Benefit Analysis , Female , Hepatitis B/etiology , Hepatitis C/etiology , Humans , Male , Middle Aged , Prevalence , Risk Factors , Sexual Behavior , United States/epidemiology
14.
Hepatology ; 24(5): 1250-5, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8903406

ABSTRACT

Significant controversy exists regarding the regulation of glucuronidation during the process of hepatic regeneration. We used a partial hepatectomy rat model to elucidate the effects of hepatic regeneration on the various components of the microsomal glucuronidation system. Hepatic microsomes were prepared by standard sucrose density centrifugation, coupled with a modified technique involving Percoll centrifugation. Microsomal uridine diphosphate (UDP)-glucuronosyltransferase (UGT) protein expression and UGT messenger RNA (mRNA) levels were measured by Western and Northern blotting. UGT enzyme activity was determined toward two prototypical aglycones, p-nitrophenol and estrone, in intact and digitonin-treated microsomes. Microsomal uptake of the cosubstrate for all glucuronidation reactions, UDP-glucuronic acid (UDP-GlcUA), was determined using a rapid-filtration assay. Microsomal enrichment after hepatectomy was preserved only when the Percoll method was used. Microsomal UGT protein expression and UGT mRNA levels were unaltered after hepatectomy. UGT enzyme activity toward estrone was unchanged 1 day posthepatectomy compared with sham laparotomy controls. Similarly, p-nitrophenol glucuronide formation was unaffected by hepatic regeneration 1, 2, and 5 days posthepatectomy when digitonin-treated microsomes were used. Glucuronidation of p-nitrophenol in intact microsomes was increased in partial hepatectomy compared with sham-operated controls at 1 and 2 days. This increase was not attributable to changes in microsomal UDP-GlcUA uptake, which was comparable in both groups. We conclude that microsomal glucuronidation, in contrast to other well characterized hepatic metabolic functions, is highly preserved during liver regeneration.


Subject(s)
Glucuronates/metabolism , Liver Regeneration , Microsomes, Liver/metabolism , Animals , Glucuronosyltransferase/genetics , Glucuronosyltransferase/metabolism , Male , NADPH-Ferrihemoprotein Reductase/metabolism , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley
15.
Biochim Biophys Acta ; 1283(2): 223-31, 1996 Sep 04.
Article in English | MEDLINE | ID: mdl-8809103

ABSTRACT

Previous studies have documented the presence of protein-mediated transport of UDP-glucuronic acid (UDP-GlcUA) in rat liver endoplasmic reticulum (ER). Measurement of uptake at varying concentrations of high specific activity [beta-32P]UDP-GlcUA has revealed the presence of a two component UDP-GlcUA transporting system. Transport at low substrate concentrations occurred predominantly via a high affinity component (K(m) = 1.6 microM), whereas a low affinity component (K(m) = 38 microM) predominated at high substrate concentrations. The K(m) for the high affinity system is in agreement with that previously published, while the low affinity component is a new finding. The uptake of UDP-GlcUA was temperature-sensitive, time dependent, and saturable for both components. The high affinity transport was affected by trans-stimulation and cis-inhibition by UDP-N-acetylglucosamine (UDP-GlcNAc); however, the same concentrations of UDP-GlcNAc had less effect on the low affinity system. In order to further study the two transport components, various inhibitors of anion transport carriers were tested. The high affinity component was strongly inhibited by 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and furosemide, while the low affinity system was less sensitive to these reagents. Dose-dependent inhibition by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) was found for both transport systems. Probenecid was found to be a weak inhibitor of both components of the UDP-GlcUA uptake. Finally, the major metabolite of 3'-azido-3'-deoxythymidine, 3'-azido-3'-deoxythymidine monophosphate (AZTMP), was able to inhibit the uptake of UDP-GlcUA by both components. The results indicate the presence of two carrier-mediated UDP-glucuronic acid transporting components in rat liver ER.


Subject(s)
Carrier Proteins/metabolism , Endoplasmic Reticulum/metabolism , Liver/ultrastructure , Uridine Diphosphate Glucuronic Acid/metabolism , 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid/pharmacology , Animals , Biological Transport/drug effects , Furosemide/pharmacology , Kinetics , Male , Osmolar Concentration , Probenecid/pharmacology , Rats , Rats, Sprague-Dawley
16.
Dig Dis ; 14(5): 304-15, 1996.
Article in English | MEDLINE | ID: mdl-8902416

ABSTRACT

Genetic hemochromatosis is an autosomal recessive disease characterized by increased intestinal iron absorption and consequent tissue iron overload. The hemochromatosis gene has been localized on the short arm of chromosome 6, in close proximity to the HLA locus, but has yet to be identified. Neither the gene product nor the pathogenetic defect have been characterized. Clinical manifestations vary according to the degree of iron overload, ranging from the asymptomatic state to the features of cirrhosis and hepatocellular carcinoma. Early diagnosis remains essential, since the survival of patients without established cirrhosis is comparable to that of the general population. Transferrin saturation and ferritin levels are suggestive of the diagnosis, but measurement of the hepatic iron concentration still remains the gold standard, despite the utilization of computerized tomography and magnetic resonance imaging. Routine phlebotomies constitute the principal therapeutic option, despite the recent preliminary data on oral iron chelators.


Subject(s)
Chromosomes, Human, Pair 6 , Hemochromatosis/genetics , Chelation Therapy , Genes, Recessive , Hemochromatosis/diagnosis , Hemochromatosis/therapy , Humans , Phlebotomy
17.
Gastroenterology ; 111(1): 193-8, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8698199

ABSTRACT

BACKGROUND & AIMS: Pathophysiological conditions such as sepsis and hepatitis are mediated by inflammatory cytokines and frequently are associated with cholestasis. The aim of this study was to determine the effect of endotoxin (lipopolysaccharide [LPS]) and cytokine administration on hepatocellular transporters involved in bile salt transport. METHODS: LPS and cytokines were administered to Sprague-Dawley rats or C57BL/6 mice, and the expression and function of hepatocyte transporters involved in bile salt secretion were examined. RESULTS: LPS caused gene expression of the hepatocyte basolateral sodium-dependent taurocholate cotransporter (Ntcp) to decrease by more than 90%. Tumor necrosis factor alpha (TNF-alpha) or interleukin (IL) 1beta also produced a time-dependent decrease in Ntcp messenger RNA levels, whereas IL-6 had no effect. LPS administration resulted in a concordant 90% reduction of basolateral protein expression of the hepatocyte sodium taurocholate cotransporter and markedly diminished sodium-dependent taurocholate uptake. Activity of the hepatocyte basolateral Na+,K+-adenosine triphosphatase (ATPase) was also decreased by 50% in a posttranslational manner after endotoxin treatment. CONCLUSIONS: Endotoxin inhibits hepatocellular sodium-dependent bile salt uptake by decreasing both expression of Ntcp and activity of the Na+,K-ATPase. The effects on Ntcp are mediated via TNF-alpha and IL-1beta. Alterations of these transporters may contribute to the cholestasis of sepsis and inflammation.


Subject(s)
Bile Acids and Salts/metabolism , Carrier Proteins/metabolism , Cytokines/adverse effects , Inflammation Mediators/adverse effects , Lipopolysaccharides/adverse effects , Liver/metabolism , Organic Anion Transporters, Sodium-Dependent , Symporters , Animals , Blotting, Northern , Blotting, Western , Carrier Proteins/genetics , Cholestasis/etiology , Cholestasis/metabolism , Cholestasis/physiopathology , Gene Expression , Interleukin-1/adverse effects , Interleukin-6/adverse effects , Male , Mice , Mice, Inbred C57BL , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Sodium-Potassium-Exchanging ATPase/metabolism , Taurocholic Acid/metabolism , Tumor Necrosis Factor-alpha/adverse effects
18.
Semin Liver Dis ; 16(2): 159-67, 1996 May.
Article in English | MEDLINE | ID: mdl-8781021

ABSTRACT

The liver is responsible for the detoxification and biliary excretion of a variety of endogenous and xenobiotic compounds and, therefore, is capable of responding to rapid fluctuations in metabolic demand. In order to accomplish this function, the hepatocyte must efficiently transport a host of substrates with wide-ranging physical-chemical properties to intracellular sites for biotransformation and subsequent secretion into the bile. The trafficking of substrates and metabolites within the liver cell is a complex process, involving the coordinated action of cellular proteins, organellar membranes, the cytoskeleton, vesicular transport pathways, and bulk convective cytoplasmic flow. This review summarizes recent developments in the field of intracellular transport, with particular reference to the metabolism of small hydrophobic and amphipathic molecular species (e.g., bilirubin, bile salts, fatty acids) by the hepatocyte.


Subject(s)
Bile Acids and Salts/metabolism , Bilirubin/metabolism , Fatty Acids/metabolism , Liver/metabolism , Animals , Biological Transport, Active , Carrier Proteins/metabolism , Humans
19.
J Consult Clin Psychol ; 64(2): 295-304, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8871414

ABSTRACT

The purpose of this study was to provide an experimental test of the theory of change put forth by A. T. Beck, A. J. Rush, B. F. Shaw, and G. Emery (1979) to explain the efficacy of cognitive-behavioral therapy (CT) for depression. The comparison involved randomly assigning 150 outpatients with major depression to a treatment focused exclusively on the behavioral activation (BA) component of CT, a treatment that included both BA and the teaching of skills to modify automatic thoughts (AT), but excluding the components of CT focused on core schema, or the full CT treatment. Four experienced cognitive therapists conducted all treatments. Despite excellent adherence to treatment protocols by the therapists, a clear bias favoring CT, and the competent performance of CT, there was no evidence that the complete treatment produced better outcomes, at either the termination of acute treatment or the 6-month follow-up, than either component treatment. Furthermore, both BA and AT treatments were just as effective as CT at altering negative thinking as well as dysfunctional attributional styles. Finally, attributional style was highly predictive of both short- and long-term outcomes in the BA condition, but not in the CT condition.


Subject(s)
Cognitive Behavioral Therapy , Depressive Disorder/therapy , Adult , Depressive Disorder/diagnosis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Psychological Tests , Treatment Outcome
20.
Trans Am Clin Climatol Assoc ; 107: 48-55; discussion 55-6, 1996.
Article in English | MEDLINE | ID: mdl-8725559

ABSTRACT

In summary, hepatocellular membranes likely play an essential role in the binding and directed trafficking of unconjugated bilirubin, and potentially of a variety of other small hydrophobic molecules. Targeting of these substrates to the endoplasmic reticulum is determined by membrane cholesterol content, surface area and integral protein binding and enzyme activity. The rate of intracellular transport potentially may be modulated by the concentration of cytosolic binding proteins, but, at least for ligandin, this protein does not appear to function primarily as an intracellular bilirubin transporter.


Subject(s)
Liver/metabolism , Animals , Bilirubin/metabolism , Biological Transport, Active , Glutathione Transferase/metabolism , Humans , In Vitro Techniques , Liver/ultrastructure , Microscopy, Electron , Models, Biological , Subcellular Fractions/metabolism
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