Increased risk for dementia in elderly psychiatric inpatients with late-onset major depression.
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Age of Onset↗
Biomedical subjects
L Karp
Publications and source records attributed to L Karp.
Decreased platelet peripheral-type benzodiazepine receptors in adolescent inpatients with repeated suicide attempts.
BACKGROUND: Peripheral-type benzodiazepine receptors (PBR) are responsible for mitochondrial cholesterol uptake, the rate limiting step of steroidiogenesis. They have been shown to be increased after acute stress, and decreased during exposure to chronic stressful conditions, and in patients with generalized anxiety disorder and post-traumatic stress disorder. In view of the proven connection between adolescent suicidal behavior and stress, we hypothesized that PBR may be decreased in the suicidal adolescent population. METHODS: We measured [3H] PK 11195 binding to platelet membrane in nine adolescent (age 13-20 years) inpatients with a history of at least three suicidal attempts and ten age-matched psychiatric inpatients with no history of suicide attempts. Suicidality was assessed with the Suicide Risk Scale (SRS), and symptom severity with the Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Overt Aggression Scale (OAS), and Impulsivity Scale (IS). RESULTS: Suicide Risk Scale scores were significantly higher in the suicidal group. The suicidal group showed a significant decrease in platelet PBR density (-35%) compared to the controls (p < 0.005). CONCLUSIONS: Our results of PBR depletion in adolescent suicide are in accordance with the findings in patients with generalized anxiety disorder and posttraumatic stress disorder and lend further support to the role of PBR in human response to chronic stress in adolescent suicide.
Adolescent↗
Platelet peripheral-type benzodiazepine in pregnancy and lactation.
The aim of the present study was to investigate the impact of hormonal changes during pregnancy and lactation on the expression of peripheral-type benzodiazepine receptors in platelet membranes. Platelet peripheral benzodiazepine receptor binding characteristics, Hamilton anxiety and depression rating Scores, and progesterone and prolactin (PRL) levels were evaluated during pregnancy and lactation in 17 pregnant women [first (n = 9) and third (n = 8) trimesters], 10 lactating women, and 8 nonpregnant women. A significant decrease (38-41%) in peripheral benzodiazepine receptor density was observed in women during the third trimester of pregnancy when compared to nonpregnant controls and women in their first trimester of pregnancy. The decrease is peripheral benzodiazepine receptors was parallel to the peak in progesterone and PRL secretion. The reduction in peripheral benzodiazepine receptor expression is hormone-dependent and may play a regulatory role geared to prevent pregnancy-related overactivity of the hypothalamic-pituitary-ovarian, hypothalamic-pituitary-adrenal, and hypothalamic-PRL axes.
Adolescent↗
Insulin-like-growth-factor-I (IGF-I) antagonizes apoptosis induced by serum deficiency and doxorubicin in neuronal cell culture.
We evaluated the effect of insulin-like growth factor (IGF)-I on neuronal cell viability and apoptosis induced by exposure to serum-free (SF) medium and to doxorubicin. In primary neuronal culture, IGF-I (0.5-2.0 microg/ml) slightly increased basal cell viability; SF medium tended to decrease viability (20-27%), and addition of IGF-I significantly antagonized this decrease (P< 0.05). In neuroblastoma (NB) SK-N-SH cell culture, IGF-I significantly increased viability (0.05-1.25 microg/ml) (P< 0.005); SF medium decreased it by 75%, and this decrease was prevented by IGF-I (0.5-1. 0 microg/ml) (P< 0.005). Flow cytometry studies showed an increased apoptosis on exposure to SF medium (88.8 vs 10.2%), which was suppressed to 38.3% by addition of IGF-I. Growth hormone (1-10 microU/ml) did not modify basal cell viability in either culture, and SF-induced cell death in NB cells. Doxorubicin (1-100 microM) caused neurotoxicity in primary and NB cultures (66-39% and 39-10% of controls, respectively), and increased apoptosis in NB cells (73. 8 vs 20.1%). IGF-I antagonized these neurotoxic/apoptotic effects (P< 0.05). This study suggests that IGF-I possesses a potent neuroprotective activity which may be involved in the resistance to doxorubicin.
Animals↗
Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin.
The functional inhibitory characteristics of the angiotensin II type 1 receptor blockers (ARB) candesartan; irbesartan; and losartan and its active metabolite EXP 3174 (EXP) were studied in rabbit aortic strips and rat portal vein preparations in vitro. Moreover, plasma-protein binding was determined, and the binding was high (>98. 5%) for all ARBs. These values were needed to relate the concentrations of the ARBs used in vitro to the nonprotein bound concentrations in clinical use. In both vascular preparations, candesartan caused a marked decrease in the maximal contractile response of the angiotensin II (Ang II) concentration-response curve. Losartan, EXP, and irbesartan caused a rightward parallel shift without any major effects on the maximal response to Ang II. The inhibitory effect of candesartan developed slowly (maximal effect after >30 minutes) and lasted >2 hours despite repeated washing of the vessels. The effect of losartan, irbesartan, and EXP had a faster onset, and most of the inhibitory effect disappeared after washing. The duration of the inhibitory effects of the ARBs were not related to lipophilicity of the compounds. Cooling of the rat portal vein preparations to 4 degrees C before administration of candesartan prevented the persistent inhibition of Ang II response seen at 37 degrees C. For the other ARBs studied, the magnitude of inhibition and the speed of recovery of the Ang II response were independent of the incubation temperature before washing. In addition, when candesartan was given to conscious rats, the inhibitory effect on Ang II-induced blood pressure responses persisted during the 24-hour period despite nondetectable plasma concentrations of candesartan at 24 hours. It is concluded that functional inhibitory characteristics of candesartan differ from those of the other ARBs tested. At clinically relevant concentrations, candesartan is an insurmountable and long-lasting antagonist of the vascular contractile responses to Ang II.
Angiotensin II↗
Electroconvulsive therapy down-regulates platelet peripheral-type benzodiazepine receptors in medication-resistant major depressed patients.
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Adult↗
Altered platelet peripheral-type benzodiazepine receptor in posttraumatic stress disorder.
Peripheral-type benzodiazephine receptors (PBR) are involved in steroidogenesis and are sensitive to stress. Reduced platelet PBR density has been demonstrated in generalized anxiety disorder (GAD), but not in obsessive-compulsive disorder (OCD). We extended this observation to another anxiety disorder, namely, posttraumatic stress disorder (PTSD). Eighteen post-Persian Gulf War PTSD patients and 17 age- and sex-matched controls were included in the study. All subjects were evaluated using the Structured Clinical Interview for DSM-III-R-Patient Version. The severity of symptoms was assessed using the DSM-III-R scale for PTSD, the Impact of Event Scale, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. [3H]PK 11195 was used to label platelet PBR. All psychological parameters (except trait anxiety) were higher in PTSD patients compared to controls. Decreased platelet PBR density (-62%; p < .001) was observed in the PTSD patients compared to controls. The reduction in PBR observed in PTSD patients was in accordance with the findings in GAD patients, but differed from those obtained in OCD patients. It is possible that the receptoral downregulation is an adaptive response aimed at preventing chronic overproduction of glucocorticoids in hyperarousal states.
Adult↗
Cytokine production in drug-free and neuroleptic-treated schizophrenic patients.
A line of evidence indicates changes of the immune system in schizophrenic patients. We investigated the production of cytokines by peripheral blood mononuclear cells (PBMCs) in drug-free and neuroleptic-treated schizophrenic patients compared to healthy, normal controls. A significant reduction in interleukin (IL)-2 production was detected in untreated schizophrenic patients (-59.6%; p < .05) as well as in IL-3-like activity (IL-3-LA) production (-27.4%; p < .05) in treated patients compared to controls. No alteration was observed in IL-1 beta production. It seems that schizophrenia is associated with diminished IL-2 production, while neuroleptic treatment interferes with the capacity of immunocompetent cells to synthesize and/or release Il-3-LA. The alteration in cytokine production did not correlate with either the severity of the disorder or the serum prolactin levels.
Adult↗
Platelet peripheral-type benzodiazepine receptor in major depression.
The peripheral-type benzodiazepine receptor (PBR) plays a major role in steroidogenesis. This receptor is sensitive to endocrine changes and stress. Antidepressants have been demonstrated to modulate adrenal and hepatic PBR in rats. To evaluate the relationship between depression and PBR, we measured platelet PBR in untreated depressed patients (n = 14) in comparison to normal controls (n = 13). Platelet PBR density (Bmax) and the dissociation constant (kd) of the receptor did not differ in the patients when compared with normal controls. Furthermore, no correlation was found between Bmax values and the severity of the depression (as measured by the Hamilton Depression Rating Scale and Beck Depression Inventory) as well as with the severity of the anxiety (as measured by the Hamilton Anxiety Rating Scale). It seems that major depression, in contrast to stress and some anxiety disorders, is not associated with alteration of PBR.
Adolescent↗
Alteration of platelet benzodiazepine receptors by stress of war.
Mitochondrial benzodiazepine receptors play a major role in steroidogenesis. The authors determined plasma cortisol levels, platelet levels of mitochondrial benzodiazepine receptors, and anxiety and depression scores in 11 civilians exposed to the Persian Gulf war. The density of mitochondrial benzodiazepine receptors was 22% and 15% lower before and during the war, respectively, than 4 weeks after the end of the war. Relief of stress led to an increase in receptors, which correlated with the improvement in anxiety but not mood.
Anxiety Disorders↗
Interaction between antidepressants and phosphoinositide signal transduction system in human platelets.
The present study was designed to evaluate the inhibitory effect of antidepressants on thrombin-induced phosphoinositide (PI) hydrolysis. Thrombin 5 units/ml induced a 100%-200% increase in platelet inositol phosphates (IPs) formation. This effect was inhibited in a dose-dependent manner by various heterocyclic antidepressants (IC50 40-170 mumol/L) The monoamine oxidase inhibitor, phenelzine, in concentrations up to 500 mumol/L, was devoid of inhibitory activity. The tricyclic antidepressants, (50 mumol/L) inhibited also thrombin-induced platelet aggregation by 32%-47%. No alteration in thrombin-induced IPs formation was detected in recovered major depressed patients (n = 15) maintained on clomipramine (75-150 mg/day). These results indicate that the heterocyclic antidepressants interfere with the thrombin-linked PI-signaling system. However, the inhibitory effect is achieved only in concentrations above the plasma concentrations obtained with therapeutic doses of these agents.
Antidepressive Agents↗
Phenotypic and genotypic characterization of Hodgkin's disease.
Although a few studies have reported clonal cytogenetic changes in Hodgkin's disease (HD), their correlation with histologic groups is poorly defined. This is because of insufficient numbers of clonally abnormal cases ascertained in each of these studies, an inherent problem associated with the cytogenetic studies of HD. In this report we present results of pathologic, phenotypic, and genetic studies on 29 HD tumors consecutively ascertained by us and the results of a comprehensive analysis of the cytogenetic data available in the literature. In our series 75% of the tumors were positive for Epstein-Barr virus (EBV) by polymerase chain reaction (PCR) assay. A higher frequency of EBV-positive tumors showed clonal karyotypic abnormalities than the EBV-negative tumors. Unlike the case in the previous reports, none of the 24 tumors studied by PCR showed the presence of t(14;18) (q32;q21)-carrying cells. From the comprehensive analysis of the literature, we identified recurring nonrandom numerical changes, deletions, and chromosome breaks in HD. Some of these are associated either with nodular sclerosis or with mixed cellular histologies. A comparison of the pattern of these nonrandom cytogenetic changes in HD and those reported for non-Hodgkin's lymphomas (NHL) identified common deletions and breaks between them. These common genetic lesions probably play a role in disease evolution.
Adolescent↗
The platelet benzodiazepine receptor is unaltered in obsessive-compulsive disorder.
Mitochondrial benzodiazepine receptors (MBR) are sensitive to anxiety and stress. The aim of the present study was to investigate whether platelet MBR are altered in untreated obsessive-compulsive disorder (OCD) patients and whether chronic treatment with clomipramine (CMI) regulates these receptors. MBR were assessed in 13 drug-free OCD patients as compared with 15 healthy controls. Seven of the 13 patients were treated with CMI (200-300 mg/day). The density and affinity of the receptors to their ligand [3H]PK 11195 in OCD patients and controls were not affected by the CMI treatment despite the clinical improvement. It seems that, in contrast to generalized anxiety disorder, OCD is not associated with alterations in platelet benzodiazepine receptors.
Adult↗
Cytokine production in anorexia nervosa.
The capacity of peripheral blood mononuclear cells (PBMCs) of anorexia nervosa (AN) patients to produce interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-3-like activity (IL-3-LA) was studied. A significantly lower (-49%, p < 0.005) capacity to synthesize IL-2 and an almost significantly impaired ability (-35%, p = 0.058) to release IL-3-LA by PBMCs of AN patients was found, as compared with cells of the control group. IL-1 production, either spontaneous or after stimulation with lipopolysaccharide (LPS), did not differ significantly between AN patients and healthy subjects. The lessened capacity to produce IL-2 was accompanied by an enhanced stimulatory activity of the patient sera on the production of this cytokine by PBMCs of healthy subjects. It is therefore suggested that the serum of AN patients contains a stimulatory factor or factors for cytokine production that compensates for the lower production of cytokines by AN PBMCs. Such a compensatory mechanism may explain why AN patients do not have an higher susceptibility to infections.
Adolescent↗
Serial phenotypic, cytogenetic and molecular genetic studies in Richter's syndrome: demonstration of lymphoma development from the chronic lymphocytic leukaemia cells.
In this report we describe a unique longitudinal study on the clinical, phenotypic, cytogenetic and molecular genetic features of malignant cells from diagnosis of chronic lymphocytic leukaemia (CLL) to the development of lymphoma and lymphomatous meningitis. CLL cells at diagnosis were CD5+, CD19+, surface IgG+, kappa+, were karyotypically abnormal and showed clonal rearrangements in the immunoglobulin heavy (IgH) and kappa light chain genes. Phenotypically leukaemic cells and lymphoma cells at RS resembled CLL at diagnosis, but showed cytogenetic evolution. Geometrically leukaemic cells and lymphoma cells retained the initial clonal rearrangements in IGH and kappa genes, but showed additional supervening clonal rearrangements in both of these genes as the disease progressed to RS. Furthermore, the c-lambda DNA showed clonal rearrangements in the leukaemic cells and lymphoma cells at RS. This complete phenotypic and genotypic analysis of tumour cells during the course of the disease demonstrates the origin of lymphoma from CLL cells through progressive cytogenetic and molecular genetic changes in CLL cells.
Blotting, Southern↗
Platelet imipramine binding and plasma cortisol levels in Israeli civilians during the Gulf War.
[3H] Imipramine binding to platelets and plasma cortisol levels were measured in nine Israeli civilians before, during, and after repeated missile attacks. Hamilton Anxiety Rating Scale (HARS), and Beck Depression Inventory (BDI) were similar before and during the war and decreased significantly after the war. A trend toward increase in platelet imipramine binding values was observed during the war when compared with the postwar values (19%; p = 0.056), and/or when compared with prewar values (26%; p = 0.063). However, one-way analysis of variance with repeated measures did not reveal a significant statistical difference [F (2,6) = p = 2.07; NS] among the three time points. A significant correlation was found between HARS score, but not BDI, and imipramine binding values in the prewar and postwar time points (r = 0.87; 0.71, respectively). Plasma cortisol levels did not alter significantly during the study period.
Adjustment Disorders↗
Platelet peripheral benzodiazepine receptors in repeated stress.
[3H]PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced (26%; P less than 0.05) density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.
Adolescent↗
Peripheral benzodiazepine receptors on platelets in chronic and detoxified alcoholics.
The effect of chronic alcoholism and detoxification treatment with disulfiram on platelet peripheral benzodiazepine receptors was studied in alcoholic males. Chronic consumption of alcohol did not alter the binding values for [3H]PK 11195, as compared to non-alcoholics. Treatment for 3 weeks with disulfiram resulted in a significant increase in the density of peripheral benzodiazepine receptors, with no alteration in the affinity of these sites to the ligand. These results might be relevant to the cellular and metabolic effects of disulfiram.
Adult↗