The effects of education in psychiatry on attitudes towards antidepressants in nursing students: A cross-sectional study.

BACKGROUND: Stigma associated with depression and antidepressants is strong among the general population but also among patients and health professionals. OBJECTIVES: This cross-sectional study is aimed at: 1) evaluating the knowledge and attitude towards antidepressant by nursing student; 2) exploring the association between instruction in psychiatry and representation of depression and antidepressants. PARTICIPANTS: 2037 undergraduate students from 10 French nursing schools were invited to participate in 2017, 1475 (73%) completed the questionnaire. METHODS: The self-report questionnaire included the Drug Attitude Inventory (DAI) and questions about representation on depression and antidepressant. Four groups of students were built: 1) pre-teaching group (PT) as a reference group, 2) clinical training in psychiatry (CT), 3) receiving mental health theoretical education (TE), 4) receiving both (CT + TE). RESULTS: The mean (standard deviation) DAI score was negative: -1.9 (±4.4) with only 40% of the nursing students conveying a positive attitude towards antidepressant. A combination of CT and TE was associated with a more positive attitude towards antidepressant in comparison with the PT condition. The CT + TE group was more prone to view antidepressants as effective and safe. CONCLUSION: There is strong stigma against depression/antidepressants among nursing student. Education combined with clinical experiences in psychiatry improved these representations.

[Membrane lipids in schizophrenia and early phases of psychosis: Potential biomarkers and therapeutic targets?] / Lipides membranaires dans la schizophrénie et la psychose débutante : de potentiels biomarqueurs et pistes thérapeutiques ?

The various roles of membrane lipids in human health has urged researchers to study their impact in neuropsychiatric diseases, especially in schizophrenia spectrum disorders and more recently in early stages of psychosis. The progress in mass spectrometry technologies now allows a more comprehensive analysis of phospholipids (PL) and their fatty acid (FA) molecular species. FA are defined by a carbon chain of variable length and are said to be unsaturated when their chain has one or more carbon-carbon double bonds. The PL are composed of a hydrophilic polar head with a phosphoric acid group and an hydrophobic part with FAs; they encompass glycerophospholipids and sphingolipids. The plasma membrane is a complex and dynamic structure consisting of a lipid bilayer composed of an outer layer and an inner layer of specific lipid composition. The permanent remodeling of membrane lipids involves phospholipases especially the phospholipase A2. Seventy percent of the brain consists of lipids from different classes and molecular species. Most of the brain lipids are composed of polyunsaturated fatty acid (PUFA)-enriched diacyl classes where omega-3 and omega-6 molecular species predominate. The balance between omega-3 and omega-6 is important for the neurodevelopment. PUFA are also involved in neurogenesis and neurotransmission. Sphingomyelin (SM) is a sphingolipid that influences inflammation, cell proliferation and lipid rafts formation. It is an important component of myelin sheaths of white matter and therefore is involved in cerebral connectivity. In rat models, deficiency in omega-3 causes abnormalities in dopaminergic neurotransmission, impacts on the functioning of some receptors (including cannabinoids CB1, glutamatergic N-methyl-D-aspartate receptor, NMDA), and increases sensitivity to hallucinogens. In contrast, omega-3 supplementation improves cognitive function and prevents psychotic-like behavior in some animal models for schizophrenia. It also reduces oxidative stress and prevents demyelination. The historical membrane hypothesis of schizophrenia has led to explore the lipids abnormality in this disorder. This hypothesis was initially based on the observation of an abnormal membrane prostaglandin production in schizophrenia caused by a membrane arachidonic acid deficiency. It has evolved emphasizing the various PUFA membrane's roles in particular regarding oxidative stress, inflammation and regulation of the NMDA receptors. In patients with mental disorders, low omega-3 index is more frequent than in the general population. This lipid abnormality could lead to myelination abnormalities and cognitive deficits observed in patients. It could also participate in oxidative stress abnormalities and inflammation reported in schizophrenia. On the other hand, low omega-3 index deficit was reported to be associated with an increased cardiovascular risk, and omega-3 supplementation may also have a positive cardiovascular impact in psychiatric patients, even more than in the general population. The presence of membrane lipid abnormalities is also found in patients during the first psychotic episode (FEP). The omega-3 supplementation improved the recovery rate and prevented the loss of gray matter in FEP. In patients at ultra-high risk to develop a psychotic disorder (UHR), omega-3 supplementation has been associated with a reduction of the rate of conversion to psychosis and with metabolic changes, such as decreased activity of phospholipase A2. However, this study has not as yet been replicated. Not all patients exhibit lipid abnormalities. Several studies, including studies from our team, have found a bimodal distribution of lipids in patients with schizophrenia. But some studies have found differences (in PUFA) in the acute phase whereas our studies (on phospholipids) are in chronic phases. It will be interesting to study in more depth the links between these two parameters. Furthermore, we identified a subgroup which was identified with a deficit in sphingomyelin and PUFA whereas others have found an increase of sphingomyelin. Individuals with this abnormal lipid cluster had more cognitive impairments and more severe clinical symptoms. Because the niacin test is an indirect reflection of arachidonic acid levels, it has been proposed to identify a subset of patients with membrane lipids anomalies. Niacin test response is influenced by several factors related to lipid metabolism, including cannabis use and phospholipase A2 activity. Despite progress, the function and impact of membrane lipids are still poorly understood in schizophrenia. They could serve as biomarkers for identifying biological subgroups among patients with schizophrenia. In UHR patients, their predictive value on the conversion to psychosis should be tested. Omega-3 supplementation could be a promising treatment thanks to its good tolerance and acceptability. It could be more appropriate for patients with PUFA anomalies in a more personalized medical approach.

Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations.

Schizophrenia is a severe mental condition in which several lipid abnormalities-either structural or metabolic-have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM-) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM- patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.

Docosahexaenoic acid promotes micron scale liquid-ordered domains. A comparison study of docosahexaenoic versus oleic acid containing phosphatidylcholine in raft-like mixtures.

The understanding of the functional role of the lipid diversity in biological membranes is a major challenge. Lipid models have been developed to address this issue by using lipid mixtures generating liquid-ordered (Lo)/liquid-disordered (Ld) immiscibility. The present study examined mixtures comprising Egg sphingomyelin (SM), cholesterol (chol) and phosphatidylcholine (PC) either containing docosahexaenoic (PDPC) or oleic acid (POPC). The mixtures were examined in terms of their capability to induce phase separation at the micron- and nano-scales. Fluorescence microscopy, electron spin resonance (ESR), X-ray diffraction (XRD) and calorimetry methods were used to analyze the lateral organization of the mixtures. Fluorescence microscopy of giant vesicles could show that the temperature of the micron-scale Lo/Ld miscibility is higher for PDPC than for POPC ternary mixtures. At 37°C, no micron-scale Lo/Ld phase separation could be identified in the POPC containing mixtures while it was evident for PDPC. In contrast, a phase separation was distinguished for both PC mixtures by ESR and XRD, indicative that PDPC and POPC mixtures differed in micron vs nano domain organization. Compared to POPC, the higher line tension of the Lo domains observed in PDPC mixtures is assumed to result from the higher difference in Lo/Ld order parameter rather than hydrophobic mismatch.

[Who are patients suffering from bipolar disorders in France? The TEMPPO survey: patients' sociodemographic and clinical characteristics data]. / Caractéristiques sociodémographiques et cliniques de patients souffrant de troubles bipolaires suivis en ambulatoire en France métropolitaine.

AIM: One of the aims of the TEMPPO study was to describe the sociodemographic and clinical characteristics of a cohort of adult outpatients with type I or type II bipolar disorders (as defined by DSM-IV criteria) in France. METHODS: TEMPPO is a multicenter, cross-sectional, non-interventional study conducted in France between November 2008 and May 2009, with a random sample of academic and private practice psychiatrists. Each psychiatrist who agreed to participate in the study had to: complete a register with data on all consecutive patients (up to 20 patients) consulting during a 2-month period and fulfilling inclusion criteria; include in the study the first five patients of the register with an on-going consultation for at least 6 months; for each of which a detailed questionnaire had been assessed, notably their sociodemographic and bipolar clinical characteristics. Adult outpatients diagnosed with bipolar disorders (BD) were enrolled if fulfilling the following inclusion criteria: man or woman, aged 18 and above, diagnosed bipolar type I or II according to DSM-IV criteria, treated (whatever the treatment strategy) or not, and followed-up for at least 6 months by the participating psychiatrist. RESULTS: One hundred and thirty-five psychiatrists included 619 patients with bipolar disorder (197 and 422 followed-up in public and private practice respectively). The estimated prevalence of patients with bipolar disorders consulting psychiatrists was 0.43%. Type I bipolar disorder was the most frequent condition (58% of the patients). As a whole, bipolar disorder was associated with severe handicap (mean global disease Clinical Global Impression [CGI]-Severity score of 4.4 and mean GAF [Global Assessment of Functioning] score of 59), with more depressive episodes than manic episodes (6 vs. 4) or hypomania (6 vs. 3), a high proportion of rapid cycles (11%), psychiatric comorbidities (45% of patients), obesity (16% of patients), libido dysfunction and associated psychotic symptoms. Current manic phase was associated with more pronounced illness severity and lowest functioning. More than half of the patients (57%) had a family history of psychiatric disorders. CONCLUSION: This study could shed some light for a better understanding of demographics and clinical patterns of patients with bipolar disorders consulting psychiatrists in France. The results emphasize the severity of bipolar disorders with mainly depressive episodes, a high proportion of rapid-cycling, comorbidities and associated psychotic symptoms; these characteristics being more marked in patients suffering from BD I. Furthermore, this study confirms the strong negative impact on social and professional life of French bipolar patients, requiring specific management in addition to the symptomatic treatment.

[Treatment practices in the management of patients with bipolar disorder in France. The TEMPPO study]. / Pratiques thérapeutiques dans la prise en charge des patients souffrant de troubles bipolaires en France. Étude TEMPPO.

TEMPPO is an observational, cross-sectional and multicentre study, initiated in the French metropolitan territory in 2009. Set up from a random sample of 135 psychiatrists, it has observed the procedures for therapeutic management of a population (n=619) of their outpatients (respectively 197 and 422 in public and private practice) with bipolar disorder type I or II disorders (DSM-IV). The patients who were followed were mostly very sick. Every patient received a pharmacological treatment. The prescription included at least one mood stabilizer or an antipsychotic (71 % atypical) in 78 % and 56 % of cases respectively. Treatment regimen changes were frequent (61 % of patients had at least one change in treatment during the last 12 months). A single molecule by therapeutic class was generally prescribed. The presence of an antipsychotic in combination therapy was often associated with the severity or difficulty of care of the patient (mixed states, severity of the global functioning impairment, manic states, high number of hospitalizations and history of suicide attempt). The combination of two antipsychotics is found only in the difficult situations of manic states. Patients with severe depressive phase are those who benefit from the combination mood stabilizer+antipsychotic+antidepressant (16 % of the sample). In this study, the prescription of antidepressants significantly differs from recommendations for good prescribing practices. Indeed antidepressants were commonly prescribed in mixed-phase (63 %), particularly as a monotherapy in 5 % of cases. It was also found in patients in euthymic phase (48 %), manic phase (12 %) and hypomanic phase (29 %). The prescription of atypical antipsychotics (monotherapy or combination) is now fully established in the management of all phases of the disease. The importance of non-pharmacological treatment is acknowledged by psychiatrists and proposed whether a psychotherapeutic support, information about the disease and/or lifestyle changes. The data collected in this study allowed to demonstrate that the participant psychiatrists have a pharmacological management of patients with bipolar disorder mostly in line with national and international guidelines.

[Therapeutic strategy of depressive episodes. Prevention of relapse risk]. / Stratégie thérapeutique des épisodes dépressifs. Prévention du risque de récidive.

Prevention of the risk of recurrence of depressive episodes is a dynamic process that begins early in the management. Although complete remission is obtained for almost half of the treated depressive episodes, a heuristic conceptual thinking apprehends depression as a potentially chronic disorder when considering relapse and recurrence prevention. Multiple actions of care have to be initiated. They are formalised, but also adjustable to the needs of a critical management period throughout the follow-up. These actions include the prescription of an antidepressant at an effective dosage. They also consider the preventative and therapeutic impact of psychotherapy. The search for residual symptoms of depression is the rule, and addition of other medication should be considered if needed. These recommendations are evidence-based in the context of recurrence prevention. Nevertheless, many other initiatives are equally important recommendations in terms of therapeutic impact. Thus, rigorous evaluation of the initial symptomatology, promotion of information on disease, health-care advices, as well as implementation of family and other networks are good-practices. Such actions should be conducted in a relationship based on a therapeutic alliance. These elements need to be adjusted and contextualised in line with the Health System, mode of medical practice and unique style of the therapist. Proactive and sustainable implementations of these guidelines are required in the context of a unique and open therapeutic relationship for both therapist and patient.

A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian).

RATIONALE: Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003). OBJECTIVES: The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian. METHODS: Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan. RESULTS: Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D(2) receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5-HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale. CONCLUSION: This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.

Reduction of extracellular dopamine and metabolite concentrations in rat striatum by low doses of acute cyamemazine.

The low incidence of extrapyramidal effects with atypical neuroleptics has been ascribed to their 5-HT(2A)- and 5-HT(2C)-serotonin receptor antagonistic properties. On the other hand, the acute increase in striatal dopamine release by submaximal dopamine D(2) autoreceptor blockade can be respectively reduced and increased by 5-HT(2A)- and 5-HT(2C)-antagonists. Cyamemazine is a neuroleptic D(2)- and 5-HT(2A)-receptor antagonist, with small antagonistic activity at 5-HT(2C) receptors and low incidence of extrapyramidal side effects. Therefore, submaximal cyamemazine was tested in rats for its acute action on the extracellular concentrations of dopamine and dopamine metabolites (DOPAC: 3,4,dihydroxyphenylacetic acid and HVA: 4-hydroxy-3-methoxy-phenyl-acetic acid) in the corpus striatum. The serotonin metabolite 5-HIAA (5-hydroxy-indole-acetic acid) was measured in parallel. Rats prepared for microdialysis (striatum) were intraperitoneally given cyamemazine 1 mg/kg, 5 mg/kg or vehicle ( n=4 in each group). Dopamine, DOPAC, HVA and 5-HIAA concentrations in perfusates under basal conditions and after stimulation by high K(+) were measured by HPLC coupled to electrochemical detection. Cyamemazine 1 mg/kg significantly reduced extracellular concentrations of basal dopamine (-77%), DOPAC (-54%), HVA (-54%) and 5-HIAA (-65%). No such effects were seen with the dose of cyamemazine 5 mg/kg or for K(+)-evoked dopamine release. In conclusion, submaximal cyamemazine can acutely reduce basal dopamine release and metabolism in the rat striatum. Such unusual action can be explained by the original pharmacological profile of cyamemazine (potent D(2)- and 5-HT(2A)-antagonist, with small antagonistic activity at 5-HT(2C) receptors). Further experiments are required to explain the low incidence of extrapyramidal side actions with cyamemazine.

[What information do patients with schizophrenia have about their illness and treatment?]. / De quelles informations les patients souffrant de schizophrénie disposent-ils sur leur maladie et leur traitement?

Improved compliance with antipsychotic medication is a major issue in schizophrenic management. For this purpose educational programs have been used, but up to now, little or no information has been gathered or published in France concerning schizophrenic patients' opinion on information they have about their disease and their treatment. Thus we conducted a survey in concert with 78 psychiatrists from the French psychiatric health service. From this cross sectional survey we assessed 336 outpatients (male: 72%; mean age: 36 +/- 10.4 years) with schizophrenia according to the DSM IV (paranoid sub type: 57%, disorganized: 12%, catatonic: 1%, undifferentiated: 12%, residual: 18%). The mean duration of the illness was 11.6 years (sd: 8.5) and the mean duration of the follow up with the same psychiatrist was 5.4 years (sd: 5.1). Patients completed a questionnaire which assessed their level of information on mental illness and treatment. The diagnosis of schizophrenia has been told to their patients by 39% of the psychiatrists, and treatment has been explained to the patients by 96% of the practitioners. Results indicate less than half of the patients (45%) felt ill, only 46% thought they knew their illness well or very well (nevertheless only 31% of them named spontaneously the diagnosis of schizophrenia or psychosis), and 61% considered that they had been given sufficient information. Most of the patients (79%) were persuaded that their treatment was useful, and 75% of patient were completely satisfied with their treatment. Surprisingly 92% reported taking their medication regularly. Most patients think that a high level of information about their illness (74%) and treatment (79%) help them to cope better with their schizophrenia. Analysis performed according to patients characteristics indicated that paranoid patients felt more ill (p = 0.035) than others, thought to know less about their illness (p = 0.0065), and were less satisfied with their treatment (p = 0.04) and their level of information (p = 0.03). Patients with a duration of their illness longer than 10 years were more convinced of the utility of their treatment (p = 0.02) and had debated more on the choice of their treatment with their psychiatrist (p = 0.047). Patients older than 35 years were more satisfied with their information (p = 0.002). More patients with atypical antipsychotics accepted to take their treatment on a regular basis (p = 0.035) compared to patients under classical neuroleptics. This survey underlines that mental health consumers' opinions can be obtained even in the field of schizophrenia, and argues in favour of further such investigations. It also highlights the need for educational programs on schizophrenia and antipsychotic medications.

What is the schizophrenic patients' level of information about their disease and their treatment?

Improved compliance with antipsychotic medication is a major issue in schizophrenic management. For this purpose educational programs have been used, but up to now, little or no information has been gathered or published in France concerning schizophrenic patients' opinion on information they have about their disease and their treatment. Thus we conducted a survey in concert with 78 psychiatrists from the French psychiatric health service. From this cross sectional survey we assessed 336 outpatients (male: 72%; mean age: 36 +/- 10.4 years) with schizophrenia according to the DSM IV (paranoid sub type: 57%, disorganized: 12%, catatonic: 1%, undifferentiated: 12%, residual: 18%). The mean duration of the illness was 11.6 years (sd: 8.5) and the mean duration of the follow up with the same psychiatrist was 5.4 years (sd: 5.1). Patients completed a questionnaire which assessed their level of information on mental illness and treatment. The diagnosis of schizophrenia has been told to their patients by 39% of the psychiatrists, and treatment has been explained to the patients by 96% of the practitioners. Results indicate less than half of the patients (45%) felt ill, only 46% thought they knew their illness well or very well (nevertheless only 31% of them named spontaneously the diagnosis of schizophrenia or psychosis), and 61% considered that they had been given sufficient information. Most of the patients (79%) were persuaded that their treatment was useful, and 75% of patients were completely satisfied with their treatment. Surprisingly 92% reported taking their medication regularly. Most patients think that a high level of information about their illness (74%) and treatment (79%) help them to cope better with their schizophrenia. Analysis performed according to patients characteristics indicated that paranoid patients felt more ill (p = 0.035) than others, thought to know less about their illness (p = 0.0065), and were less satisfied with their treatment (p = 0.04) and their level of information (p = 0.03). Patients with a duration of their illness longer than 10 years were more convinced of the utility of their treatment (p = 0.02) and had debated more on the choice of their treatment with their psychiatrist (p = 0.047). Patients older than 35 years were more satisfied with their information (p = 0.002). More patients with atypical antipsychotics accepted to take their treatment on a regular basis (p = 0.035) compared to patients under classical neuroleptics. This survey underlines that mental health consumers' opinions can be obtained even in the field of schizophrenia, and argues in favour of further such investigations. It also highlights the need for educational programs on schizophrenia and antipsychotic medications.

[Dysthymic disorders]. / Troubles dysthymiques.

Long lasting, low intensity depressive episodes have been diversely integrated according to the classifications types or the psychodynamic points of view. The concept of anxious persistent lasting depression, neurotic depressive states, neurotic depression ... have been unified into the dysthymic disorder category of the DSM classification. This concept unification have been a topic of dispute considering that dysthymic disorder was a restrictive, heterogeneous an extensively comorbid diagnosis. Nevertheless the definition of this category offers the opportunity to place the notions of temperament, personality, adjustment disorder. Including dysthymic disorders as a category inside of the mood disorders classification suggests the interest of using an antidepressive medication in presence of chronic depressive states not included in the major depressive disorder category.

[When and how to stop anxiolytic drugs]. / Quand et comment arrêter les anxiolytiques?

The anxiolytics withdrawal constitutes a frequently desirable therapeutic situation in which it is necessary to integrate clinical data related to the disorder for which they were prescribed as well as the pharmacological and psychological aspects. Personality features and emotional environment of the patient are to be considered. This withdrawal follows a first step in which the anxiolytics were initially prescribed. This situation happens in medicine in multiple clinical situations. However, because of the phenomena of tolerance and dependence but also according to the efficacy of the anti-depressants in most anxiety disorders, benzodiazepines are described in France as over-prescribed molecules. General rules of prescription are a prelude to a good withdrawal process. This last must always be prevented especially when the dosage is high occurring after a long duration treatment. A good guideline for the initial prescription is a good ticket to anticipate the withdrawal time.

[Is the anxious patient dependent?]. / L'anxieux est-il dépendant?

To answer the question: is the anxious a dependant person, it is necessary to define to what extend behaviour depends on pathology. The difficulty in answering this question relies on the fact that these two phenomenons interact with each other. The comorbidity analysis allows a descriptive point of view. It shows a higher incidence of these troubles when occurring together, compared to a general population. Nevertheless, the comorbidity approach does not give any information on the nature of the links between anxiety and dependence. The causality models depend on the theory they use. Furthermore, unity between anxiety and dependence disorders does not exist; it is then certainly a mistake to consider their link in a unique way. Three main hypothesis are usually used. The neurobiology point of view supposes a link between brain structures, neurofunctioning, anxiety and dependence disorders. Some authors suggest a general addictive propensity of brain functioning, especially in cases of anxiety disorders. Lastly, the psychopathological analysis can be useful in the understanding of dependence behaviour in case of anxiety.

Protein-polysaccharide complexes as surfactants.

A study has been made of surface pressure (pi) and maximum shear stress (Ps) (at a constant shear rate) of decane-water interface on which bovine serum albumin (BSA) and its complexes with dextran sulfate (DS) were adsorbed. The pi values have been monitored by the Wilhelmy plate technique. The Ps values have been measured with a surface viscoelastometer. The changes of pi with time for BSA and BSA-DS complexes in general takes place in two stages which can be attributed to two corresponding limiting factors: diffusion of molecules (or particles) to the interface, and rearrangements of adsorbed molecules. The diffusion-controlled stage for the BSA-DS complexes was found to be several times as long as for BSA. The relaxation time of the second stage is a function of protein concentration Cp, for the complexes having maximum value at Cp = 10(-3)-10(-2) g/l. These maxima are coincident with midpoints of the surface pressure isotherms. The latter one of the BSA-DS complexes is shifted towards greater protein concentrations in comparison with that of BSA. The Ps assumes maximum values at Cp corresponding to the midpoints of surface pressure isotherms. These values for the complexes are 15-20 times greater the that for free BSA.

[Physico-chemical properties of the complexes of bacitracin with DNA and its effect on the process of transcription in vitro]. / Fiziko-khimicheskie svoistva kompleksov batsitratsina s DNK i vliianie ego na protsess transkriptsii in vitro.

The aim of the present paper was to study the action of one of the peptide antibiotics, bacitracin, as the regulator of gene activity at the transcription level. Therefore the commercial bacitracin has been fractionated into two main parts by paper chromotography. These two fractions have been identified as bacitracin A (biologically active) and bacitracin F (biologically inactive). The binding of both fractions to DNA has been studied. It has been shown that bacitracin A stabilizes DNA to a lesser degree than bacitracin F does. DNA-bacitracin complexes are formed in the major groove of the DNA helix by hydrogen bonds. The analysis of the the obtained experimental data allows us to suppose that bacitracin binding to DNA has a very specific character and that this antibiotic may act as the regulator of gene activity.

An ultrasound receiver with programmable time gain control.

An ultrasound receiver with programmable time gain control (TGC) has been developed. The TCG curve is synthesized from sequentially gated analog switches, each of which controls receiver gain over a range of 1cm. Diagnostic studies using a receiver with the programmable TGC curve show improved results in the amplitude equalization of received echoes and in the output display.