Consecutive Weeks (consecutive + week)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Social withdrawal behaviors in nonhuman primates and changes in neuroendocrine and monoamine concentrations during a separation paradigm,

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2005
Kristine Erickson
Abstract This study investigated relationships between withdrawal behaviors in rhesus macaques and changes in monoamine metabolite and endocrine concentrations during repeated psychosocial stress. Rhesus monkeys (N,=,71) experienced maternal separation in which four separations took place during four consecutive weeks. Behavioral observations were made, as well as plasma concentrations of cortisol and cerebrospinal fluid concentrations of the serotonin, dopamine, and norepinephrine metabolites were obtained. Animals were assigned to high, moderate, and low withdrawal groups, defined using baseline durations of withdrawal behaviors. Highly withdrawn animals showed less reduction than nonwithdrawn animals in serotonin metabolite concentrations over repeated separations. Highly withdrawn macaques also failed to significantly reduce cortisol concentrations across separation weeks. More adaptation in central serotonin functioning and cortisol concentrations was seen in nonwithdrawn primates than in highly withdrawn primates; these findings have implications for increased risk of developing anxiety disorders in highly inhibited children. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 46:331,339, 2005. [source]


Plasma Concentrations of Risperidone and Olanzapine during Coadministration with Oxcarbazepine

EPILEPSIA, Issue 5 2005
Maria Rosaria Muscatello
Summary:,Purpose: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. Methods: OXC, at a dosage of 900,1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2,6 mg/day) and 13 on olanzapine (5,20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. Results: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 ± 3.6 ng/ml at baseline to 4.8 ± 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 ± 7.5 to 24.7 ± 7.4 ng/ml), and olanzapine (from 26.5 ± 5.7 ng/ml at baseline to 27.8 ± 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Conclusions: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes. [source]


Use of Percutaneous Electrical Nerve Stimulation (PENS) in the Short-term Management of Headache

HEADACHE, Issue 4 2000
Hesham E. Ahmed MD
Objective.,To evaluate the short-term effects of percutaneous electrical nerve stimulation (PENS) in the management of three types of chronic headache. Background.,Traditional electroanalgesic therapies have been reported to be effective in the management of acute headache symptoms. However, no controlled studies have been performed in patients with chronic headache. Methods.,Thirty patients with either tension headache, migraine, or posttraumatic headache symptoms of at least 6 months' duration were randomized to receive PENS (needles with electricity) or "needles alone" according to a crossover study design. All treatments were administered for 30 minutes, three times a week for 2 consecutive weeks with 1 week off between the two different treatments. For the PENS treatments, an alternating electrical stimulation frequency of 15 and 30 Hz was used. Pain, activity, and sleep scores were assessed using a 10-cm visual analog scale, with 0 corresponding to the best and 10 to the worst, during the 48-hour period prior to the beginning of the two treatments, immediately before and after each treatment session, and 48 hours after completing each treatment modality. Results.,Compared with the needles alone, PENS therapy was significantly more effective in decreasing the overall VAS pain scores for tension-type headache, migraine and posttraumatic headache (58%, 59%, and 52% versus 20%, 15%, and 20%, respectively). Similarly, PENS therapy produced greater improvement in the patients' physical activity (41% to 58% for PENS versus 11% to 21% for needles only) and quality of sleep (41% to 48% for PENS versus 12% to 20% for needles only). However, there were no differences in the pattern of the response to PENS therapy among the three headache groups. Conclusions.,Percutaneous electrical nerve stimulation appears to be a useful complementary therapy to analgesic and antimigraine drugs for the short-term management of headache. Interestingly, the analgesic response to PENS therapy appears to be independent of the origin of the headache symptoms. [source]


Effects of dietary caffeine on EEG, performance and mood when rested and sleep restricted,

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2008
Michael A. Keane
Abstract Rationale: Until recently, little account had been taken of the confounding effects of caffeine withdrawal and withdrawal reversal when examining the net effects of dietary caffeine. Objectives: By including a manipulation involving sleep restriction, the present study aimed to extend recent findings from research in which caffeine withdrawal and withdrawal reversal were controlled. The main aims of the study were to examine the net effects of caffeine, as well as its potential restorative effects following sleep restriction, on EEG, performance and mood. Method: A randomised cross-over design was used in which 15 participants alternated weekly between ingesting placebo and caffeine (1.75,mg/kg) three times daily for four consecutive weeks following either usual sleep or sleep restriction. EEG activity was measured at 32 sites during eyes closed, eyes open and performance of a vigilance task. Results: Modest effects of caffeine were found in the delta and beta bandwidths, but no main effects of caffeine were observed in the theta or alpha bandwidths. Overall, the effects of caffeine on EEG activity were relatively few, weak and inconsistent, and no evidence was found of net restorative effects of caffeine for any outcome variables. Conclusions: The findings do not support the use of caffeine as a means for enhancing human function or as an antidote to the negative effects of sleep loss. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo-controlled study,,The Bergen District Nursing Home Study (BEDNURS)

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2008
Sabine Ruths
Abstract Background Despite modest efficacy, unpredictable individual utility, and a high rate of adverse effects, behavioural and psychological symptoms of dementia (BPSD) are common determinants for antipsychotic drug therapy in nursing home patients. Aims To explore the impact on BPSD of stopping long-term antipsychotic treatment in nursing home patients with dementia. Methods Fifty-five patients (43 women; mean age 84.1) taking haloperidol, risperidone, or olanzapine for BPSD were randomly assigned to cessation (intervention group, n,=,27) or continued treatment with antipsychotic drugs (reference group, n,=,28) for 4 consecutive weeks. The Neuropsychiatric Inventory (NPI) Questionnaire was used to examine changes in behavioural and psychological symptoms. Results By study completion, 23 of the 27 intervention group patients were still off antipsychotics. Symptom scores (NPI) remained stable or even improved in 42 patients (intervention group, 18 out of 27; reference group, 24 out of 28; p,=,0.18). As compared to patients with stable or improved symptom scores, patients with behavioural deterioration after antipsychotic cessation used higher daily drug doses at baseline (p,=,0.42). Conclusion A large share of elderly nursing home patients on long-term treatment with antipsychotics for BPSD, do well without this treatment. Standardized symptom evaluations and drug cessation attempts should therefore be undertaken at regular intervals. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Effect of tourniquet pressure and intra-individual variability on plasma fibrinogen, platelet P-selectin and monocyte tissue factor

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2000
J. L. Ritchie
Small differences in levels of certain haemostatic components may be clinically significant. It is important therefore to eliminate potential sources of confounding variability. This study investigated the effect of removing tourniquet pressure prior to sample collection on plasma fibrinogen levels, platelet P-selectin and monocyte tissue factor expression. Blood was collected from the right arm under maintained tourniquet pressure and from the left arm following the release of pressure once the vein was sufficiently inflated for insertion of a needle. Whole blood was labelled within one hour of venepuncture to allow analysis of platelet P-selectin and monocyte tissue factor by flow cytometry. Plasma fibrinogen levels were analysed in samples stored at ,70 °C, for all individuals at the end of the study using a method based on the Clauss technique. Intra-individual variability for each of the components was assessed by collecting samples under tourniquet pressure from four individuals on the same day on three consecutive weeks. Intra-individual variations were greater than assay CVs for all three components. There were no significant differences between the two tourniquet methods of collection for fibrinogen, P-selectin or tissue factor. In conclusion, there is no reason not to use a tourniquet during collection of blood for analysis of plasma fibrinogen, platelet P-selectin or monocyte tissue factor. [source]


Effect of Antipsychotic Withdrawal on Behavior and Sleep/Wake Activity in Nursing Home Residents with Dementia: A Randomized, Placebo-Controlled, Double-Blinded Study The Bergen District Nursing Home Study

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004
Sabine Ruths MD
Objectives: To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia. Design: Randomized, placebo-controlled, double-blind trial. Setting: NHs in Bergen, Norway. Participants: Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms. Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks. Measurements: Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy. Results: After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24-hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI-Q. One patient was restarted on antipsychotics. Conclusion: Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long-term effect of these changes is not known. The NPI-Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies. [source]


Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: A multicenter study

JOURNAL OF CLINICAL APHERESIS, Issue 1 2001
Takashi Shimoyama
Abstract Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 ± 3.60 mg prednisolone (mean ± SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 ± 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse. J. Clin. Apheresis. 16:1-9, 2001. © 2001 Wiley-Liss, Inc. [source]


Inflexible and Indifferent Alcohol Drinking in Male Mice

ALCOHOLISM, Issue 7 2010
Heidi M. B. Lesscher
Background:, Alcoholism is characterized by compulsive alcohol intake, but this critical feature of alcoholism is seldom captured in preclinical studies. Here, we evaluated whether alcohol-preferring C57BL/6J mice develop compulsive alcohol drinking patterns, using adulteration of the alcohol solution with quinine, in a limited access choice paradigm. We assessed 2 independent aspects of compulsive drinking: (i) inflexible alcohol intake by testing whether mice would drink bitter alcohol solutions if this was their only source of alcohol and (ii) indifferent drinking by comparing intake of aversive and nonaversive alcohol solutions. Methods:, Male C57BL/6J mice consumed alcohol for 2 or 8 consecutive weeks. The alcohol solution was then adulterated with graded quinine concentrations, and the effect on alcohol intake was determined. Results:, C57BL/6J mice rapidly developed compulsive alcohol drinking patterns. Adulteration of the alcohol solution with an aversive quinine concentration failed to reduce intake, indicative of inflexible drinking behavior, after only 2 weeks of alcohol experience, although quinine adulteration did suppress the acquisition of alcohol drinking in naďve mice. After 8 weeks of alcohol consumption, the mice also became indifferent to quinine. They consumed an aversive, quinine-containing alcohol solution, despite the simultaneous availability of an unadulterated alcohol solution. Prolonged alcohol ingestion did not alter the sensitivity to the bitter taste of quinine itself. Conclusion:, These findings demonstrate the staged occurrence in mice of 2 distinct behavioral characteristics of alcoholism, i.e., inflexible and indifferent alcohol drinking. [source]


Behavioral and endocrinological evaluation of music therapy for elderly patients with dementia

NURSING & HEALTH SCIENCES, Issue 1 2004
Mizue Suzuki rn
Abstract The present study investigated the effectiveness of music therapy for dementia patients using endocrinological and behavioral evaluations. The study comprised 10 patients with senile dementia who received music therapy; six had Alzheimer's dementia and four had vascular dementia. Music therapy was performed twice a week for 8 consecutive weeks (16 sessions). As a result, total scores on the Mini-Mental State Examination (MMSE) did not significantly change, but the scores of a subscale, ,language', improved significantly. According to the Multidimensional Observation Scale For Elderly Subjects (MOSES), scores for ,irritability' decreased significantly. Regarding changes in salivary chromogranin A (CgA) levels, the average was significantly decreased before session 16 compared to after this. These results suggest that the combination of endocrinological measurements, behavioral evaluations and functional assessment methods are useful in evaluating the effects of music therapy in persons with senile dementia. [source]


Allergic rhinitis in the child and associated comorbidities

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-II 2010
Tania Sih
Sih T, Mion O. Allergic rhinitis in the child and associated comorbidities. Pediatr Allergy Immunol 2010: 21: e107,e113. © 2009 John Wiley & Sons A/S Allergic rhinitis (AR) typically presents after the second year of life, but the exact prevalence in early life is unknown. AR affects 10,30% of the population, with the greatest frequency found in children and adolescents. It appears that the prevalence has increased in the pediatric population. As the childs' immune system develops between the 1st and 4th yr of life, those with an atopic predisposition begin to express allergic disease with a clear Th2 response to allergen exposure, resulting in symptoms. In pediatric AR, two or more seasons of pollen exposure are generally needed for sensitization, so allergy testing to seasonal allergens (trees, grasses, and weeds) should be conducted after the age of 2 or 3 years. Sensitization to perennial allergens (animals, dust mites, and cockroaches) may manifest several months after exposure. Classification of AR includes measurement of frequency and duration of symptoms. Intermittent AR is defined as symptoms for <4 days/wk or <4 consecutive weeks. Persistent AR is defined as occurring for more than 4 days/wk and more than 4 consecutive weeks. AR is associated with impairments in quality of life, sleep disorders, emotional problems, and impairment in activities such as work and school productivity and social functioning. AR can also be graded in severity , either mild or moderate/severe. There are comorbidities associated with AR. The chronic effects of the inflammatory process affect lungs, ears, growth, and others. AR can induce medical complications, learning problems and sleep-related complaints, such as obstructive sleep apnea syndrome and chronic and acute sinusitis, acute otitis media, serous otitis media, and aggravation of adenoidal hypertrophy and asthma. [source]


Fexofenadine, an H1-receptor antagonist, partially but rapidly inhibits the itch of contact dermatitis induced by diphenylcyclopropenone in patients with alopecia areata

THE JOURNAL OF DERMATOLOGY, Issue 2 2006
Kazumoto KATAGIRI
ABSTRACT Antihistamines have been used for the treatment of not only allergic diseases such as allergic urticaria and rhinitis, but also of eczematous skin diseases because of their anti-pruritic effects. Moreover, the pruritus associated with eczematous diseases is considered to be induced, in part, by histamine. However, it is unclear whether antihistamines inhibit the itch of eczematous diseases in the absence of topical corticosteroids. In this study, we investigated the anti-pruritic effect of the antihistamine, fexofenadine, on the itch of contact dermatitis that was induced by topical application of diphenylcyclopropenone for the treatment for alopecia areata. Thirteen patients with alopecia areata, who had been treated weekly with topical immunotherapy with diphenylcyclopropenone for 3 months to 2 years, recorded the severity of their itching on a visual analog scale before and 3, 6, 12, 24, 48 and 72 h after application of diphenylcyclopropenone for 4 consecutive weeks. Seven patients took fexofenadine during the first and third weeks, and six patients took fexofenadine during the second and fourth weeks. The severity of itching reached a maximum 6,12 h after the induction of the contact dermatitis in most of the patients. However, fexofenadine partially but rapidly reduced the severity of itching for 72 h during the entire period of treatment in the absence of topical corticosteroids. Our results suggest that fexofenadine can be beneficial in the daily management of patients with itching due to eczematous disease. [source]


Evaluations of toxicity of Turraeanthus africanus (Méliaceae) in mice

ANDROLOGIA, Issue 6 2009
D. Massoma Lembč
Summary Turraeanthus africanus (Meliacaeae) is known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties. However, no extensive safety studies have been conducted on these extracts to date. The aim of this study was to evaluate toxicity of the aqueous extract of Turraeanthus africanus (Meliacaeae) after oral and intraperitoneal administration in mice. The acute toxicity was evaluated after single daily administration of the aqueous extract orally at doses of 0, 5, 10, 15, 20, 30 g kg,1 or by the intraperitoneal route at doses of 0, 3, 6, 9, 12 g kg,1 of raw material. The subacute toxicity was evaluated only by the intraperitoneal route for 6 weeks at doses of 1.5, 3, 6 g kg,1 of raw material. Oral doses up to 30 g kg,1 of the aqueous extract of Turraeanthus africanus (TA) did not produce mortality or significant changes in the general behaviour and gross appearance of internal organs of rats. However, the intraperitoneal administration of the aqueous extract of Turraeanthus africanus caused dose-dependent lethal effects. The acute intraperitoneal toxicity (LD50) of TA extract in mice was 7.2 g kg,1. In subacute toxicity in mice, after the intraperitoneal administration of TA extract for 6 consecutive weeks, the feed consumption was significantly affected at the dose 3 g kg,1 with P < 0.05 and at the dose 6 g kg,1 with P < 0.001 and consequently had significant effect with P < 0.05 in body weight of animals. Level of triglyceride of treated animals lowered at dose 1.5 g kg,1 with P < 0.001 and at dose 3 g kg,1 and 6 g kg,1 with P < 0.05. Total cholesterol level of treated animals lowered at dose 1.5 g kg,1 with P < 0.005 and at dose 3 and 6 g kg,1 with P < 0.001. HDL cholesterol level of treated animals lowered up to dose 6 g kg,1 with P < 0.05 while levels of LDL cholesterol, serum and tissue creatinine of treated animals lowered at dose 3 g kg,1 and dose 6 g kg,1 with P < 0.05. Serum protein level of treated animal enhanced at dose 1.5 g kg,1 and at dose 6 g kg,1 with P < 0.05 while tissue creatinine level of treated animal enhanced with P < 0.001. The histology of liver, kidney and lung of the treated mice indicated morphological change of these organs (data not shown). No significant difference was observed during treatment concerning the haematological parameters. The results suggest that the plant is not toxic through the oral route in mice and that parenteral administration should be avoided. [source]


Photochemical reflectance index as a mean of monitoring early water stress

ANNALS OF APPLIED BIOLOGY, Issue 1 2010
V. Sarlikioti
Water stress in plants affects a number of physiological processes such as photosynthetic rate, stomatal conductance as well as the operating efficiency of photosystem II (PSII) and non-photochemical quenching (NPQ). Photochemical reflectance index (PRI) is reported to be sensitive to changes in xanthophyll cycle which occur during stress and could possibly be used to monitor changes in the parameters mentioned before. Therefore, the aim of this study was to evaluate the use of PRI as an early water stress indicator. Water stress treatment was imposed in a greenhouse tomato crop. CO2 assimilation, stomatal conductance, light-adapted and dark-adapted fluorescence as well as PRI and relative water content (RWCs%) of the rooting medium were repeatedly measured. The same measurements were also performed on well-irrigated plants that acted as a reference. The experiment was repeated in four consecutive weeks. Results showed a strong correlation between RWCs% and photosynthetic rate, stomatal conductance, NPQ and operating efficiency of PSII but not with PRI when the whole dataset was considered. Nevertheless, more detailed analysis revealed that PRI gave a good correlation when light levels were above 700 µmol m,2 s,1. Therefore, the use of PRI as a water stress indicator cannot be independent of the ambient light conditions. [source]


Rituximab may form a complex with iGm, mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis C virus,induced vasculitis

ARTHRITIS & RHEUMATISM, Issue 12 2009
Damien Sčne
Objective To report on 6 cases of hepatitis C virus (HCV),induced mixed cryoglobulinemia (MC) vasculitis in patients who developed severe systemic reactions after rituximab infusion, and to report the results of the in vitro analysis of the underlying immunologic mechanisms. Methods Twenty-two HCV-infected patients with MC vasculitis received rituximab infusions (a low-dose protocol cycle with 375 mg/m2/week for 4 consecutive weeks in 18 patients and a high-dose protocol cycle with 1,000 mg on days 1 and 15 in 4 patients). Systemic drug reactions following rituximab infusion were recorded and analyzed clinically and immunochemically. Results Six of 22 patients (27.3%) experienced systemic drug reactions after rituximab infusion. Four patients developed a severe flare of MC vasculitis 1 or 2 days after rituximab infusion. Two patients developed serum sickness syndrome 7 and 9 days after the first 1,000 mg rituximab infusion. Compared with patients without drug reactions, those with drug reactions had higher mixed cryoglobulin levels (mean ± SD 1.4 ± 0.82 gm/liter versus 0.71 ± 0.77 gm/liter; P = 0.0475) and lower C4 levels (mean ± SD 0.02 ± 0.006 gm/liter versus 0.07 ± 0.07 gm/liter; P = 0.02), and more of them received 1,000 mg high-dose rituximab protocol (50% versus 6.25%; P = 0.046). In vitro immunochemical assays showed that rituximab formed a complex with the cryoprecipitating IgM, that had rheumatoid factor (RF) activity. Moreover, the in vitro addition of rituximab to serum containing an RF-positive IgM, type II mixed cryoglobulin was associated with visibly accelerated cryoprecipitation. Conclusion In HCV-associated MC vasculitis, rituximab may form a complex with RF-positive IgM,, leading to accelerated cryoprecipitation and to severe systemic reactions. Rituximab should be administered with caution in MC vasculitis, with use of the 375 mg protocol and plasma exchanges prior to rituximab infusion in patients with high baseline levels of mixed cryoglobulin. [source]


Decreased biliary excretion of tributylmethyl ammonium in cholestyramine pretreated rats due to reduced formation of ion-pair complexes with hepatic bile salts

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2007
M. K. Choi
Abstract The hypothesis that higher molecular weight (MW) quaternary ammoniums (QAs) form lipophilic ion-pair complexes with bile salts in the liver, and are subsequently excreted into bile via a canalicular transporter, P-gp, was re-examined in the present study for its validity. The biliary excretion of tributylmethyl ammonium (TBuMA), a QA with a MW of 200, in bile salt-depleted rats was determined. Depletion was induced by a daily oral administration of a resin, cholestyramine, at a dose of 0.5,g/kg for 2 consecutive weeks, which decreased the concentration of total bile salts in the liver by 38%. When TBuMA was administered intravenously (12,µmol/kg) to these rats, the plasma level, area under the plasma concentration-time curve (AUC), systemic clearance (CL) and volume of distribution (Vss) of the compound remained unchanged, whereas bile flow (23.03 vs 16.94,µl/min, p<0.05) and biliary clearance (CLbile, 12.75 vs 5.34,ml/min/kg, p<0.01) were decreased significantly. These results implied the biliary clearance of TBuMA in rats with bile salt depletion was significantly decreased as a result of decreased ion-pair complexation of TBuMA. The above results are consistent with our hypothesis and the existence of a MW threshold (i.e. 200±50 for rats) for the biliary excretion of QAs. Copyright © 2007 John Wiley & Sons, Ltd. [source]


Acute treatment outcomes in patients with bipolar I disorder and co-morbid borderline personality disorder receiving medication and psychotherapy

BIPOLAR DISORDERS, Issue 2 2005
Holly A Swartz
Objective:, Patients suffering from both bipolar I disorder and borderline personality disorder (BPD) pose unique treatment challenges. The purpose of this matched case,control study was to compare acute treatment outcomes of a sample of patients who met standardized diagnostic criteria for both bipolar I disorder and BPD (n = 12) to those who met criteria for bipolar I disorder only (n = 58). Method:, Subjects meeting criteria for an acute affective episode were treated with a combination of algorithm-driven pharmacotherapy and weekly psychotherapy until stabilization (defined as four consecutive weeks with a calculated average of the 17-item version of the Hamilton Rating Scale for Depression and Bech-Rafaelsen Mania scale totaling ,7). Results:, Only three of 12 (25%) bipolar-BPD patients achieved stabilization, compared with 43 of 58 (74%) bipolar-only patients. Two of the three bipolar-BPD patients who did stabilize took over 95 weeks to do so, compared with a median time-to-stabilization of 35 weeks in the bipolar-only group. The bipolar-BPD group received significantly more atypical mood-stabilizing medications per year than the bipolar-only group (Z = 4.3, p < 0.0001). Dropout rates in the comorbid group were high. Conclusions:, This quasi-experimental study suggests that treatment course may be longer in patients suffering from both bipolar I disorder and BPD. Some patients improved substantially with pharmacotherapy and psychotherapy, suggesting that this approach is worthy of further investigation. [source]