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Di-n-butyl phthalate activates constitutive androstane receptor and pregnane X receptor and enhances the expression of steroid-metabolizing enzymes in the liver of rat fetuses.

The plasticizer di-n-butyl phthalate (DBP) is a reproductive toxicant in rodents. Exposure to DBP in utero at high doses alters early reproductive development in male rats. Di-n-butyl phthalate also affects hepatic and extrahepatic enzymes. The objectives of this study were to determine the responsiveness of steroid-metabolizing enzymes in fetal liver to DBP and to investigate the potential of DBP to activate nuclear receptors that regulate the expression of liver enzymes. Pregnant Sprague-Dawley rats were orally dosed with DBP at levels of 10, 50, or 500 mg/kg/day from gestation days 12 to 19; maternal and fetal liver samples were collected on day 19 for analyses. Increased protein and mRNA levels of CYP 2B1, CYP 3A1, and CYP 4A1 were found in both maternal and fetal liver in the 500-mg dose group. Di-n-butyl phthalate at high doses also caused an increase in the mRNA of hepatic estrogen sulfotransferase and UDP-glucuronosyltransferase 2B1 in the dams but not in the fetuses. Xenobiotic induction of CYP3A1 and 2B1 is known to be mediated by the nuclear hormone receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR). In vitro transcriptional activation assays showed that DBP activates both PXR and CAR. The main DBP metabolite, mono-butyl-phthalate (MBP) did not interact strongly with either CAR or PXR. These data indicate that hepatic steroid- and xenobiotic-metabolizing enzymes are susceptible to DBP induction at the fetal stage; such effects on enzyme expression are likely mediated by xenobiotic-responsive transcriptional factors, including CAR and PXR. Our study shows that DBP is broadly reactive with multiple pathways involved in maintaining steroid and lipid homeostasis.

Animals↗

Lamotrigine treatment for post-stroke pathological laughing and crying.

Pathologic laughing and crying (PLC) is a common distressing and socially disabling condition in stroke patients. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), have been increasingly recognized as the treatment of choice for pathologic crying (PC). However, little is known about etiologies and other treatment options for various clinical manifestations of PLC. This case report illustrates the beneficial effect of lamotrigine, a novel antiepileptic drug with antidepressant and mood-stabilizing properties in post-stroke PLC. A 60-year-old woman developed PLC after an ischemic stroke affecting the left frontal and temporal lobes. She was treated with lamotrigine initially at the dose of 50 mg a day, which was gradually increased to 100 mg a day over a 4-week period. There was a significant and rapid recovery in both laughing and crying components of PCL with lamotrigine treatment. The symptoms of pathologic laughing have shown a better response to lamotrigine than PC. Controlled investigations are needed to evaluate the beneficial as well as the differential effects of lamotrigine on PLC.

Crying↗

Humor as the focal point of treatment for forensic psychiatric patients.

Framed as a qualitative case study based on constructivist notions, the research being reported evaluates the Humor Group, a unique treatment modality evoking therapeutic change by engaging male forensic psychiatric patients and nursing students in humorous activities. The group's meaning for patient health was investigated by cross-analyzing data collected from patient and student questionnaires, in-depth patient interviews, and naturalistic observations made by the researcher during the group's 4-year tenure. The Humor Group structure and format are offered as guides for undertaking similar attempts to rein in humor's healing potential in other settings and with other populations.

Adolescent↗

Behavioral observations before, during, and after brief isolation (time-out).

Four adult, chronic psychotic inpatients were observed before, during and after the contingent application of time-out. Time-out was a part of their individual treatment programs, and consisted of placement in a furnitureless room for 15 minutes. Observations were made of 16 behaviors grouped into seven categories; these categories included both consequated and nonconsequated behaviors. Observation sessions lasted for 15 minutes with interval recording of each behavior for the first 10 seconds of every 30-second block. Results for each subject were analyzed by means of three-way factorial ANOVAs, and indicated the following: a) three subjects exhibited significant differences in response frequency before, during, and after time-out that were consistent across all instances of their being placed in time-out; b) the particular behaviors that reliably varied with the observation conditions for one subject were not the same as those which reliably varied for another subject; c) two subjects significantly increased the frequency of their consequated responses during time-out in spite of the fact that time-out was effective as measured by a significantly lower emission rate after time-out compared to before time-out.

Adult↗

The effect of cyclosporine on ornithine decarboxylase induction with mitogens, antigens, and lymphokines.

Ornithine decarboxylase (ODC) is the initial enzyme in polyamine synthesis. An increase in ODC activity is associated with increased RNA, DNA, and protein synthesis. We have used the induction of ODC by mitogens and alloantigens in human peripheral blood lymphocytes as an intracellular marker of protein synthesis and lymphocyte activation. The immunosuppressive agent cyclosporine was found to inhibit both the mitogen and alloantigen stimulated induction of ODC in lymphocytes in a manner that parallels inhibition of subsequent 3H-thymidine incorporation. When purified T lymphocytes were stimulated with mitogen alone, minimal ODC activity was detected. The addition of 5% monocytes, human Interleukin-1 (IL-1), or T cell growth factor (IL-2) enhanced mitogen-induced ODC activity in T lymphocytes 4-10-fold. Cyclosporine inhibited the induction of ODC when T lymphocytes were combined with monocytes or growth factors. We conclude that (1) the induction of ODC in human lymphocytes by mitogen and alloantigen is inhibited in the presence of cyclosporine; (2) the induction of ODC activity in purified T lymphocytes requires the presence of both mitogen and monocytes or their products; (3) IL-1 and IL-2 can supplement for monocytes and augment the phytohemagglutinin induction of ODC in T lymphocytes; and (4) cyclosporine inhibits ODC induction in T lymphocytes stimulated with mitogen in the added presence of monocytes, IL-1, or IL-2. The inhibition of ODC induction and polyamine synthesis by cyclosporine adds insight into its mode of action on the mechanisms involved in early T cell activation.

Cyclosporins↗

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Education, Nursing, Continuing↗

Positive psychological measure: constructing and evaluating the reliability and validity of a Chinese Humor Scale applicable to professional nursing.

The nursing profession has generally accepted humor as beneficial to health care. As nursing has always emphasized holistic care and the importance of individual needs, the profession values the ability of humor to positively affect all aspects of a patient's well being. The purposes of this study were to develop a "Chinese Humor Scale (CHS)" for the nursing profession and then test its reliability and validity. The 405 individuals selected for participation in this study included nursing on-the-job students from a medical university and professional nurses practicing at four hospitals in north Taiwan. Researchers developed a list of 57 key humor measures which were filled out and returned by study participants. An evaluation of results using Cronbach's alpha coefficients demonstrated good consistency (alpha=.93) for the developed CHS. Intercorrelations amongst the four sub-scales were generally quite low, indicating each sub-scale measures dimensions relatively distinct from one another (r=.24 approximately .48, both p's<.001). The CHS was tested using item analysis. The scale was constructed in accordance with exploratory factor analysis (EFA) (K.M.O.=.92). Thirty CHS items, categorized under the four indices of "humorous creativity", "tendency to laugh", "perceptivity to humor", and "humorous attitude", were found to explain 55.42% of total variances. The CHS was found to provide good validity using a content validity index (CVI) developed by five experts. The results of this study provide encouraging evidence for the construct validity and reliability of the proposed humor scale and support its application by nursing educators and clinicians to further test and assess concepts related to humor. Further research is needed to explore more fully the implications of humor in nursing.

Adolescent↗

The effect of humorous movies on inpatients with chronic schizophrenia.

We assessed the impact of humorous movies on psychopathology, anxiety, depression, anger, social functioning, insight, and therapeutic alliance in schizophrenia inpatients. Twenty-nine psychiatric inpatients in open wards participated in the study. The study group viewed humorous and the control group viewed neutral movies daily for 3 months. Participants were assessed before and after viewing movies with the Positive and Negative Symptom Scale, Calgary Depression Scale, the State-Trait Anxiety Inventory, the State-Trait Anger Expression Inventory-2, the Multinomah Community Ability Scale, the Insight and Treatment Attitude Questionnaire, and the Working Alliance Inventory. Reduced levels of psychopathology, anger, anxiety, and depression symptoms and an improvement in social competence were revealed in the study group. No changes were observed in treatment insight or working alliance. Video films are a practical and cost-efficient means of entertainment that seem to have a positive effect on patient morale, mood, and mental status.

Activities of Daily Living↗

Mirtazapine treatment for pathological laughing and crying after stroke.

Selective serotonin reuptake inhibitors (SSRIs) have been recognized as the treatment of choice for pathological laughing and crying (PLC), which is a common, distressing condition that follows stroke. There have been few reports about other treatment options for PLC. Here, the authors report rapid responses to mirtazapine in two patients with poststroke PLC who failed to respond to SSRIs or bupropion. In the first case, a 63-year-old woman with severe long-standing crying spells that had persisted for 3 months responded well to low-dose mirtazapine within a few days; she could not tolerate citalopram or sertraline. In the second case, both the laughing and crying spells of a 64-year-old woman were improved within a few days of mirtazapine administration, after they had not responded to bupropion. This is one of the first reports to suggest that mirtazapine may be an alternative to SSRIs for treating poststroke PLC.

Antidepressive Agents↗