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Biomedical subjects

A Weizman

Publications and source records attributed to A Weizman.

At least 19 recordsLinked to original sources
PubMed2006

Aggressive behavior and HPA axis hormones after social isolation in adult rats of two different genetic animal models for depression.

In the current study we explored behavioral and endocrinological effects of exposure to social isolation during adulthood in two different genetic animal models of depression, the Flinders Sensitive Line (FSL), and their controls, Sprague-Dawley (SD) rats and the Wistar-Kyoto (WKY) strain and their controls, Wistar rats. Behavioral patterns of the different strains in coping with an intruder were studied in the "aggression" or resident-intruder test. We also measured basal plasma levels of the hypothalamic-pituitary-adrenal (HPA) axis hormones corticosterone and ACTH and their levels after chronic stress (isolation). Significant alterations in the levels of HPA hormones after social isolation were noted in the "depressed-like" strains. There were no significant behavioral differences between FSL and SD rats in the "aggression" test. In contrast, WKY rats exhibited less frequent aggressive-like and social behavior compared to Wistar controls. The results suggest that the FSL and WKY strains, both genetic animal models of depression, exhibit separate patterns of HPA axis modulation and aggressive-like behavior after social isolation. These different patterns may reflect two different types of depression. An "avoidant" or socially inhibited type of depressive-like behavior is seen most clearly in the WKY strain.

Adaptation, Physiological↗
PubMed2006

Stress hormones and emotion-regulation in two genetic animal models of depression.

Children of depressed parents often exhibit emotion-regulation deficits, characterized by either excessive withdrawal or approach strategies toward the mother. The current study examined behavioral and physiological emotion-regulation in preweanling pups (postnatal day 17-19) belonging to two different genetic animal models of depression, Wistar-Kyoto (WKY) and Flinders Sensitive-Line (FSL) rats. The study also examined the effects of stress on the two animal models, hypothesizing an interactive effect of hereditary vulnerability and exposure to stress. Chronic-stress was simulated by providing limited bedding to the dam and litter for a week, in the early postnatal period. Acute-stress was generated by exposure to an adult male rat, an ethologically valid stressor. Emotion-regulation of the pups was examined using a Y-maze preference test and radioimmunoassay of Hypothalamic-Pituitary-Adrenal (HPA) axis hormones (corticosterone & adreno-corticotropin/ACTH). WKY and FSL pups exhibited reduced approach-behavior toward the dam, an emotion-regulation profile reminiscent of avoidant attachment evident in many children of depressed parents. In contrast, the two animal models did not show similar HPA axis activity. FSL pups exhibited markedly lower ACTH levels compared to controls, while WKY pups did not differ from controls. With regard to the stress manipulations, the limited-bedding condition had no effect, while the acute-stressor induced overall effects on all groups, with more pronounced reactivity evident in the WKY and FSL pups. Taken together, the experiments indicate a similar behavioral profile of the two strains at the preweanling period, while suggesting HPA dysfunction in only one of the strains.

Adrenocorticotropic Hormone↗
PubMed2006

Cocaine, but not amphetamine, short term treatment elevates the density of rat brain vesicular monoamine transporter 2.

We compared the effect of 5 days D-amphetamine (5 mg/kg/day i.p.) and cocaine (15 mg/kg/day i.p.) administration on the vesicular monoamine transporter 2 (VMAT2) density in rat brain. VMAT2 expression was assessed by [(3)H]dihydrotetrabenazine high affinity binding. Cocaine administration led to significant increases in VMAT2 density in both prefrontal cortex (+40%, p < 0.01) and striatum (+23%, p < 0.05), while amphetamine did not affect VMAT2 expression. The upregulation of VMAT2 may serve as compensatory mechanism aimed to enhance the vesicular monoamine storage capacity.

Amphetamine↗
PubMed2006

Elevated platelet vesicular monoamine transporter 2 in former heroin addicts maintained on methadone.

The brain vesicular monoamine transporter (VMAT2) is essential for neuronal monoamine storage and regulation of monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Opioids induce increase of dopamine release in limbic structures. In the present study we assessed the VMAT2 pharmacodynamic characteristics using high affinity [(3)H]dihydrotetrabenazine (TBZOH) binding to platelets of former male heroin addicts maintained on methadone (n = 12) compared to age-matched healthy controls (n = 13). A significant increase (19%, p < 0.05) in platelet VMAT2 density (Bmax) was observed in the methadone treated patients compared to controls. There was no significant difference in the affinity of [(3)H]TBZOH to its platelet binding site. The increased VMAT2 density may reflect a compensatory attempt to prevent vesicular depletion due to chronic methadone exposure.

Blood Platelets↗
PubMed2006

Homocysteine levels in adolescent schizophrenia patients.

Homocysteine is a sulfur containing amino acid that has been widely investigated for its putative role in cardiovascular and neuropsychiatric disorders. It has been suggested that homocysteine has implications especially in young, male schizophrenia patients. In this prospective case-control study, we compared plasma homocysteine levels in a group of adolescent schizophrenia inpatients (aged 14-21 years; n=23) to normal healthy controls (n=51). Mean plasma homocysteine levels were significantly higher in the patient group than in the control group (15.40+/-2.00 and 9.78+/-0.33 micromol/L, respectively, p<0.032). The difference was almost entirely attributable to the male schizophrenia subgroup (18.18+/-5.65 in male patients vs. 10.31+/-5.33 micromol/L in female patients). The group x sex interaction was statistically significant (p=0.0035). These data indicate that a subgroup of male adolescent schizophrenia patients has high homocysteine blood levels. The role of homocysteine in the pathophysiology of adolescent-onset schizophrenia merits further investigation.

Adolescent↗
PubMed2006

Factors associated with self-evaluated severity of illness and quality of life in male Israeli asthmatic soldiers.

OBJECTIVE: To evaluate whether the asthmatic condition and quality of life of male asthmatic Israeli soldiers deteriorate during army service. METHOD: We retrospectively assessed 178 asthmatic soldiers during service using an adapted version of the Mini Asthma Quality of Life Questionnaire, and compared it to their condition before service. The participants responded additionally to questionnaires assessing psychosocial resources and adjustment to illness. RESULTS: The self-evaluated degree of asthma disease severity (SEDOAD) of the participants deteriorated in the army compared to before service. Soldiers with mild SEDOAD during service, compared to soldiers with severe (and in most cases also moderate) SEDOAD, had less severe medically evaluated and self-evaluated asthma before service. Mild SEDOAD participants showed, additionally, lower inclination towards active seeking of asthma-related information, more favorable health care-related attitudes, less unfavorable effects of their illness on military and extra-military functioning, greater reported pre-enlistment optimism, and a greater belief in their ability to cope successfully with their asthma during service. CONCLUSION: SEDOAD and the quality of life during service are associated not only with pre-enlistment asthma severity, but also with the manner in which the soldier perceives the influence of the illness on his health condition, and the manner in which he copes with this influence.

Adult↗
PubMed2005

The effect of psychostimulants on [3H]dopamine uptake and release in rat brain synaptic vesicles.

Amphetamine and its derivatives are psychostimulants active at the plasma membrane monoamine transporters. In the present study we assessed the interaction of parachloroamphetamine, D-amphetamine, fenfluramine and methylendioxymethamphetamine with brain vesicular monoamine transporter using purified rat striatal synaptic vesicles. All four psychostimulants inhibited vesicular [(3)H]dopamine uptake in a competitive and dose-dependent manner and had no effect on [(3)H]dihydrotetrabenazine binding. At higher concentrations the drugs enhanced [(3)H]dopamine vesicular efflux. Parachloroamphetamine was the most potent agent while methylendioxymethamphetamine was the weakest one. The vesicular activities may be relevant to their neurotoxicity.

Animals↗
PubMed2005

Circulatory neurosteroid levels in underweight female adolescent anorexia nervosa inpatients and following weight restoration.

Nineteen female adolescent inpatients diagnosed with anorexia nervosa, restricting type (AN-R) and 16 non-eating disordered (ED) controls were assessed for plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and cortisol levels, and for eating-related and non-eating-related psychopathology. AN-R patients were assessed at admission, 1 month and 4 months following hospitalization. The non-ED controls were assessed once. No baseline between-group differences were found in plasma cortisol, DHEA, and DHEA-S levels, whereas the patient group had a significantly lower Cortisol/DHEA-S ratio and elevated scores on most psychopathological parameters. A significant increase was found in the body mass index of the AN-R patients at 4 months post-hospitalization, accompanied by a decrease in plasma cortisol levels and a trend towards decreased Cortisol/DHEA and Cortisol/DHEA-S ratios, whereas no change occurred in psychopathology. The difference in Cortisol/DHEA-S ratio between AN-R patients and non-ED controls, and the different patterns of change in cortisol vs. DHEA(-S) levels following weight restoration, may in part account for the feeding difficulties in AN, particularly during refeeding.

Adolescent↗
PubMed2005

Relationships between serotonin transporter promoter polymorphism, platelet serotonin transporter binding and clinical phenotype in suicidal and non-suicidal adolescent inpatients.

Relationships between the serotonin transporter promoter polymorphism (5-HTTLPR), platelet serotonin transporter (SERT) binding and clinical phenotype were examined in 32 suicidal and 28 non-suicidal Ashkenazi Israeli adolescent psychiatric inpatients. The 5-HTTLPR polymorphism was not associated with transporter binding or with suicidality or other clinical phenotypes. However, in the suicidal group, a significant positive correlation between platelet SERT density and anger scores (n=32, r=.40; p=.027) and a negative correlation between platelet count and trait anxiety (n=32, r=-.42; p=.034) were observed.

Adolescent↗
PubMed2004

DRD4 receptor gene exon III polymorphism in inpatient suicidal adolescents.

Some studies have suggested possible association of the dopamine receptor subtype 4 (DRD4) gene exon III 48 bp repeat polymorphism with novelty seeking behavior. As suicidal behavior in adolescents is linked to risk taking behavior, we evaluated the association of suicidality with DRD4 polymorphism in Israeli inpatient suicidal adolescents. Sixty-nine inpatient adolescents who recently attempted suicide were assessed by structured interview and rating scales for detailed clinical history, diagnoses, suicide intent and risk, impulsivity, violence, and depression. The frequency of DRD4 alleles was compared between the suicidal inpatients and 167 healthy control subjects. No significant association between the DRD4 polymorphism and suicidal behavior was found. Analysis of the suicide-related measures demonstrated a significant difference in depression severity between suicidal inpatients homozygote and heterozygote for the DRD4 alleles (p=0.003). The relevance of this finding to increased depression severity in suicidal adolescents, if replicated, is as yet unclear.

Adolescent↗
PubMed2004

The relation between latent inhibition and symptom-types in young schizophrenics.

Latent inhibition (LI), retarded conditioning to a stimulus that has been previously repeatedly presented without reinforcement, was examined in young schizophrenics and normal controls using a within-subject visual search task. Healthy controls exhibited the usual LI effect. LI was potentiated in schizophrenics who simultaneously exhibited high levels of negative symptoms and low levels of positive symptoms. Schizophrenic groups with other combinations of positive and negative symptoms did not differ from controls. The pattern of data suggests that past inconsistencies in the LI-schizophrenia literature may be the result of opposing processes that are associated with positive and negative symptoms.

Adolescent↗
PubMed2004

Clozapine in the treatment of obsessive-compulsive symptoms in schizophrenia patients: a case series study.

INTRODUCTION: Obsessive-compulsive (OC) symptoms have been observed in a substantial proportion of schizophrenic patients. There are some reports describing the appearance de novo or reemergence of preexisting OC symptoms under clozapine (CLZ) therapy. However, there are also reports describing a positive effect of CLZ therapy in OC schizophrenic patients. It seems that comorbid OC symptoms are common among CLZ-treated refractory schizophrenic patients and are likely to be an integral part of their illness. The complex nature of the treatment response in this group of schizophrenic patients is as yet unclear. The effects of CLZ on OC symptoms may vary, with evidence of improvement in some and worsening among others. METHODS: The present case series study describes our experience with CLZ as a sole agent (n = 10) or in combination with serotonin reuptake inhibitors (n = 5), in schizophrenic patients with prominent OC symptomatology. RESULTS: Systematic analysis of clinical features of our patients, as well as findings in the literature to date, led us to suggest some factors that may predict response to CLZ treatment in treatment-resistant schizophrenic patients with prominent OC symptoms: 1) schizophrenic patients who began to exhibit OC symptoms within the course of the psychotic process need and might to be successfully treated with CLZ alone; 2) when OC symptomatology preceded the development of schizophrenic process, CLZ monotherapy is inefficient and may even worsen OC symptoms; therefore, it should be treated concomitantly with specific anti-obsessive agents; 3) in both groups there is a definite dose-related pro-obsessive influence of CLZ when it is given in high doses. DISCUSSION: Further controlled investigations in a larger cohort of OC schizophrenic patients are needed to substantiate our hypothesis. OCD:Obsessive-compulsive disorder OCS:Obsessive-compulsive symptoms SRI:Serotonin reuptake inhibitors

Adult↗
PubMed2004

Lack of plasma norepinephrine cyclicity, increased estradiol during the follicular phase, and of progesterone and gonadotrophins at ovulation in women with premenstrual syndrome.

In healthy women, plasma norepinephrine (NE) has a cycle with the highest levels occurring at ovulation and early luteal phase. We examined plasma NE cyclicity in premenstrual syndrome (PMS) patients as compared to controls, its relation to estradiol (E(2)), progesterone (P), luteinizing hormone and follicle-stimulating hormone, and the correlation of these parameters with the PMS symptoms. Lack of NE cyclicity was observed in PMS patients. In controls, peak NE levels occurred at ovulation and early luteal phase. In PMS, serum E(2) was higher during the follicular phase, while P and gonadotrophins were higher especially at ovulation and the luteal phase. In the late luteal phase, E(2) levels were lower in PMS patients than in controls. A negative correlation was observed between the area under the curve for E(2) in the luteal phase and PMS somatic and mental scores. Plasma NE showed a negative correlation with abrupt mood swings, impatience, nervousness, tiredness, weakness, apathy, and headache. These data suggest that lack of NE cyclicity characterizes PMS, some symptoms being related to low E(2) levels during the late luteal phase and decreased noradrenergic activity at ovulation and the luteal phase.

Adult↗
PubMed2003

Cysteine-induced hypoglycemic brain damage: an alternative mechanism to excitotoxicity.

Central neural damage caused by L-cysteine (L-Cys) was first reported more than 30 years ago. Nevertheless, the exact mechanisms of L-Cys-mediated neurotoxicity are still unclear. Preliminary study in mice demonstrated that, following L-Cys injection, animals developed tachypnea, tremor, convulsions, and death in conjunction with documented hypoglycemia. The aim of the present study was to further investigate the mechanism of L-Cys-mediated hypoglycemic effect and neural damage. Neonatal ICR mice (n=6) were injected with L-Cys (0.5-1.5 mg/g body weight [BW]), and their blood glucose and insulin levels were determined up to 90 min following the injection. Experiments were repeated in chemically (streptozotocin [STZ]) pancreatectomized animals. Brain histology was assessed. Mice injected with L-Cys exhibited dose-dependent neurotoxicity and higher mortality as compared with controls. L-Cys (1.2-1.5 mg/g BW) caused severe hypoglycemia (glucose<42 mg/dl) ( P<0.001). In STZ-treated (diabetic) animals, L-Cys (1.5 mg/g BW) increased plasma insulin levels 2.3-fold and decreased serum glucose levels by 50% ( P<0.01). Brain histology revealed destruction of as much as 51% of hippocampal neurons in the L-Cys-treated mice but not in the glucose-resuscitated animals. These findings suggest that L-Cys injection can cause pronounced hypoglycemia and central neural damage which is glucose reversible. Since L-Cys is chemically different from the other excitatory amino acids (glutamate and aspartate), L-Cys-mediated neurotoxicity may be connected to its hypoglycemic effect.

Animals↗
PubMed2003

Oral health and treatment needs of institutionalized chronic psychiatric patients in Israel.

The aim of the study was to examine the oral health and treatment needs of chronically hospitalized psychiatric patients in Israel. Ten percent of the patients hospitalized for more than 2 years in the 18 psychiatric institutions in Israel were selected at random. The dental status (DMF-T index) was calculated, demographic and medical data were retrieved from the files. Of the 431 patients examined (250 men, 181 women, average age 54 years) 312 patients had only partial natural dentition. The average DMF-T score was 26.74 (out of 32), one of the highest in the literature. The caries component accounted for 2.3% of the DMF-T, the missing teeth component 72% and the restored teeth component 5%. There was an adverse correlation between age and caries and between duration of hospitalization and number of teeth. The average number of carious and missing teeth was higher than in the healthy population. No all-edentulous patients had dentures. These findings confirm the urgent need for an intervention program to improve dental health care in high-risk, difficult-to-treat, psychiatric chronic inpatients.

Adolescent↗
PubMed2003

NQO2 gene is associated with clozapine-induced agranulocytosis.

Clozapine is a dibenzodiazepine neuroleptic with atypical pharmacological and clinical profiles. Treatment with this drug may be complicated with agranulocytosis (AGR). It is likely that defective oxidative mechanism may be the cause of AGR. A candidate gene, dihydronicotinamide riboside (NRH) quinone oxidoreductase 2 (NQO2), which is involved in detoxification of drugs, was selected. This gene has been mapped to the short arm of chromosome six. The gene was studied by single-strand conformation polymorphism analysis and direct sequencing in 98 schizophrenic patients that were treated with clozapine. Eighteen of these patients developed AGR. Ten polymorphisms in the coding regions, in intron 1, and in the promoter region were found, two of which were novel. Comparisons of the polymorphisms in the first intron in AGR patients and controls suggested that this site might be connected with AGR. Quantitative reverse transcriptase-polymerase chain reaction analysis showed that the level of NQO2 mRNA is low in AGR patients compared with the control group. Such a reduction in message suggests that the NQO2 gene may be involved in the development of clozapine-induced AGR.

Agranulocytosis↗
PubMed2002

Association between flupenthixol treatment and emergence of manic symptoms.

BACKGROUND: Flupenthixol is an antipsychotic drug with known mood-elevating properties. Its propensity to induce manic symptoms has not been investigated. METHODS AND RESULTS: We describe six patients, four with schizophrenia and two with bipolar disorder, in whom flupenthixol treatment was associated with emergence of manic symptoms. CONCLUSIONS: Patients treated with flupenthixol should be carefully monitored for the emergence of manic symptoms.

Adult↗