Biocomposite from polylactic acid and lignocellulosic fibers: structure-property correlations.

PLA biocomposites were prepared using three corn cob fractions and a wood fiber as reference. The composites were characterized by tensile testing, scanning electron microscopy (SEM) and polarization optical microscopy (POM). Micromechanical deformation processes were followed by acoustic emission measurements. The different strength of the components was proved by direct measurements. Two consecutive micromechanical deformation processes were detected in composites containing the heavy fraction of corncob, which were assigned to the fracture of soft and hard particles, respectively. The fracture of soft particles does not result in the failure of the composites that is initiated either by the fracture of hard particles or by matrix cracking. Very large particles debond easily from the matrix resulting in catastrophic failure at very low stresses. At sufficiently large shear stresses large particles break easily during compounding, thus reinforcement depending on interfacial adhesion was practically the same in all composites irrespectively of initial fiber characteristics.

Gender-related urocortin 1 and brain-derived neurotrophic factor expression in the adult human midbrain of suicide victims with major depression.

In postmortem brains of patients with major depression, the expression of corticotrophin-releasing factor (CRF) is enhanced and that of brain-derived neurotrophic factor (BDNF) decreased. In mice over-expressing neuronal CRF (an animal model for depression) the expression of urocortin 1 (Ucn1) in the non-preganglionic Edinger-Westphal nucleus (npEW) is strongly down-regulated. Therefore, we hypothesized that an altered activity of Ucn1 neurons in the npEW would contribute to the pathogenesis of major depression. To test this hypothesis we measured Ucn1 mRNA and BDNF mRNA levels in the npEW of seven male and four female, drug-free suicide victims with major depression, and compared the data with those obtained from 10 male and seven female individuals without neurological and psychiatric disorders (controls). We show that compared with controls, the Ucn1-mRNA level in npEW neurons is about 9.12 times higher in male but unchanged in female suicide victims. Furthermore, BDNF mRNA expression in microdissections of npEW was 3.36 times lower in male suicide victims, but 5.27 times higher in female victims, compared with controls. Our data also show that male suicide victims had almost 11.47 times more Ucn1 and 4.26 times less BDNF mRNA in the npEW than female suicide victims. We discuss the significance of these data for npEW Ucn1 and BDNF, and propose that altered expressions of Ucn1 and BDNF in the npEW contribute to the pathogenesis of major depression and/or suicidality in a gender-specific manner.

Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics.

The prevalence of diabetes mellitus and metabolic syndrome is higher in patients with schizophrenia than in the normal population. Atypical antipsychotic drugs are used in psychiatry since the beginning of 1990. These drugs differ from the "typical" antipsychotics used previously, as they have less extrapyramidal side effects, and because of this they are tolerated better, but are associated with weight-gain and disturbances in carbohydrate metabolism. Ghrelin is an orexigen hormone partaking in body weight regulation. It is produced in the enteroendocrine P/D1 cells of the gastric mucosa and secreted to the circulation. The aim of our study was to determine ghrelin levels of atypical antipsychotic-treated patients in relationship with their body mass index (BMI) and carbohydrate metabolism. We measured the fasting serum ghrelin levels in 56 patients (male/female: 16/40, age mean+/-S.D.: 50.6+/-5.6 years) treated with atypical antipsychotics (clozapine, olanzapine, risperidon and quetiapine), and in 75 healthy control subjects, age and gender matched (RIA Linco, USA) in relationship with their BMI and their fasting and 75 g OGTT 120 min blood glucose values. The serum ghrelin levels of the patient group were notably higher (1333+/-659 pg/ml) than in the control group (368+/-103, p<0.0001; Mann-Whitney). We found no difference among the four antipsychotics in weight-gain, diabetes prevalence and the serum ghrelin levels. The BMI of the patient group was significantly higher (29.3+/-7.2 kg/m2 versus 24.3+/-3.7 kg/m2, p<0.0001; Mann-Whitney); 32% of them had blood glucose abnormality (18/56). There was no difference between the ghrelin levels in diabetic and non-diabetic patients. We found a significant negative linear correlation between the serum ghrelin and BMI (r=-0.35, p=0.0078; Spearman), the ghrelin and fasting blood glucose (r=-0.32, p=0.015) and OGTT 75 g 120 min blood glucose levels (r=-0.27, p=0.036). The orexigen effect of elevated serum ghrelin levels can contribute to the weight-gain and high diabetes prevalence associated with atypical antipsychotic treatment. The link between atypical antipsychotic treatment and elevated serum ghrelin levels is unknown so far, but a dysregulation of the central feedback mechanism can be hypothesised.

Serotonergic genes and suicidality.

Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of depressive illness and suicidal behavior. Studies have shown that the number of brain and platelet serotonin transporter binding sites are reduced in patients with depression and in suicide victims, and that the density of 5-HT2A receptors is increased in brain regions of depressed in suicide victims and in platelets of depressed suicidal patients. Genes that code for proteins, such as tryptophan hydroxylase, 5-HT transporter, and 5-HT2A receptor, involved in regulating serotonergic neurotransmission, have thus been major candidate genes for association studies of suicide and suicidal behavior. Recent studies by our group and by others have shown that genetic variations in the serotonin-system-related genes might be associated with suicidal ideation and completed suicide. We have shown that the 102 C allele in 5-HT2A receptor gene was significantly associated with suicidal ideation (chi2 = 8.5. p < .005) in depressed patients. Patients with a 102 C/C genotype had a significantly higher mean HAMD item #3 score (indication of suicidal ideation) than T/C or T/7 genotype patients. Our results suggest that the 102T/C polymorphism in 5-HT2A receptor gene is primarily associated with suicidal ideation in patients with major depression and not with depression itself. We also found that the 5-HT transporter gene S/L polymorphism was significantly associated with completed suicide. The frequency of the L/L genotype in depressed suicide victims was almost double of that found in control group (48.6% vs. 26.2%). The odds ratio for the L allele was 2.1 (95% CI 1.2-3.7). The association between polymorphism in serotonergic genes and suicidality supports the hypothesis that genetic factors can modulate suicide risk by influencing serotonergic activity.

Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims.

BACKGROUND: There is evidence indicating that serotonin uptake and density of 5-HT2A receptors are altered in brain regions of depressed suicide victims and in platelets of depressed suicidal subjects. The present investigation tested the hypothesis that these changes in the serotonergic system in depressed suicide victims are trait rather than state markers and associated with a polymorphism in respective candidate genes. METHODS: Two polymorphic variants (102T/C polymorphism and His452Tyr functional polymorphism) of the 5-HT2A receptor gene and a functional polymorphism in the 5' regulatory region of the 5-HT transporter gene, have been determined in genomic DNA obtained from postmortem brain samples of 24 depressed suicide victims and 31 control subjects of the same ethnic background. In a subset of subjects, density (Bmax) of 5-HT uptake sites (labeled with 3H-paroxetine) and of 5-HT2A receptors (labeled with 3H-ketanserin) was also determined in prefrontal cortex samples. RESULTS: The major finding of this study was a significantly higher frequency of the 5-HT transporter gene long (L) allele (chi 2 = 3.9, df = 1; p = .048) in depressed suicides. No significant differences between suicides and controls were observed for the 102T/C polymorphism and His452Tyr polymorphism of 5-HT2A receptor gene. The density of 3H-paroxetine binding sites tended to be higher in subjects expressing the short (S) allele of 5-HT transporter gene. Furthermore, there was a significant difference in serotonin transporter binding sites between the genotype S/S and combined genotypes S/L and L/L. CONCLUSIONS: Our finding provides the first evidence suggesting that a functional polymorphism in the regulatory region of serotonin transporter gene may be associated with suicide in depressed subjects.

Growth-associated protein (GAP-43), its mRNA, and protein kinase C (PKC) isoenzymes in brain regions of depressed suicides.

The aim of this study was to investigate whether the previously observed adaptive changes in the monoaminergic receptors in post-mortem brains of depressed suicide victims are associated with alteration in some functional proteins involved in serotonergic neuronal signalling, namely PKC and GAP-43. Selected regions from ten brains of antidepressant-free depressed suicide victims and ten matched controls were used to examine the levels of GAP-43 protein, GAP-43 mRNA and PKC isoenzymes by Western blotting with monoclonal antibodies specific for these proteins. A major finding of the study was a significant decrease in GAP-43 protein levels and its mRNA expression in prefrontal cortex (BA9) (by 24% and 34%, respectively) of suicide brains compared to controls. No significant changes were found in GAP-43 protein or its mRNA in frontopolar cortex (BA10), amygdala, substantia nigra or putamen. Levels of PKC isoenzymes had a heterogenous regional distribution but were not significantly altered in any of the regions examined. Given the role of GAP-43 in the establishment and reorganization of synaptic connections, the finding of selective reduction of this protein in prefrontal cortex suggests that a dysfunctional synaptic organization in this region may be associated with depression and suicidal behaviour. This study provides the first evidence of an alteration in a protein related to the neuronal plasticity in the brain of depressed suicide victims.

Alteration of protease levels in different brain areas of suicide victims.

Numerous recent studies found that proteases play a major role in brain function. In addition to their role in protein turnover, they have modulatory functions and an important role in apoptosis, pathological changes, and other mechanisms. To explore possible differences in brain protein metabolism of suicide victims, we examined the activity of two proteases, cathepsin D and calpain (I and II combined), in eleven discrete areas of postmortem brain tissue of 21 victims of suicide and of 31 age- and sex-matched control subjects without a history of psychiatric or neurological disease. The levels of functionally important amino acids in five of these areas were also measured. Cathepsin D activity was found to be lower in two of eleven regions of brains of suicide victims, the parahippocampal cortex and the medial hypothalamus, by 26% and 27%, respectively. Calpain activity was lower in two different areas tested, 29% in the medulla oblongata and 26% in the lateral prefrontal cortex, and was 18% higher in the midbrain. There were no significant differences in the other areas (globus pallidus, hippocampus, amygdala, caudate nucleus, ventral tegmental area, and nucleus accumbens). Protease distribution was regionally heterogeneous--the levels in the globus pallidus were low, and in the hippocampus high, with about a two-fold difference. The length of the postmortem period for obtaining tissue, the storage time of the frozen tissue, and the age of the subject had no apparent influence on the results obtained. Although there was a tendency toward higher levels of aspartate and glycine in brain areas from suicide victims, the difference was not significant. The variations among individual brains were greater in amino acid levels than in protease levels. The findings indicate the possible role of protein metabolism in depressive or suicidal behavior.

Platelet rich plasma serotonin content in patients suffering from different psychiatric disorders.

Platelet rich plasma serotonin contents were examined using HPLC-EC method in patients suffering from different anxiety states and compared to age matched healthy controls. We have found significant increase of PRP serotonin level in the group of schizophrenic patients and in patients suffering from dementia compared to controls. PRP serotonin content was significantly lower in heavy drinkers but in patients suffering from panic disorder did not differ significantly from the controls.

Serologically verified hantavirus infections in Hungary.

Between 1987 and 1993 the etiological diagnosis of haemorrhagic fever with renal syndrome (HFRS) of 55 patients was confirmed using hantavirus-specific serology. The geographical distribution of cases indicated that at least two different territories of Hungary are endemic for hantaviruses. These possible natural foci are different from, but overlapping with the region endemic for tick-borne encephalitis virus. Patients sera were shown to react differently with reagents prepared from different hantaviruses, indicating that different types are present simultaneously in both natural foci.

[Buspirone: a new possibility in the treatment of anxiety]. / Buspiron: a szorongás kezelésének új lehetösége.

Buspiron an azaspirodecanedione, heterocyclic compound which, although structurally unrelated to the benzodiazepines, possesses comparable anxiolytic activity. Because buspirone lacks hypnotic, anticonvulsant and muscle relaxant properties, it has been termed "anxioselective". It seems unlikely to generate the problems of dependence, abuse and rebound. It does not impair psychomotor or cognitive performance and appears to have no additive effect with other CNS-active agents, particularly alcohol. Clinical trials and studies of buspiron suggest that it is an effective treatment for the relief of symptoms of anxiety, especially in patients in whom daytime alertness is particularly important.

A double-blind comparison of nefazodone, imipramine, and placebo in major depression.

BACKGROUND: Nefazodone is a 5-HT2-receptor antagonist and serotonin (5-HT) selective reuptake inhibitor. This study evaluates the safety and efficacy of nefazodone in patients with major depressive disorder (MDD) in comparison to imipramine and placebo treatments. It also compares two dose ranges of nefazodone to investigate its optimal dose range. METHOD: Nefazodone was evaluated in a 6-week, double-blind trial of novel design involving 180 patients meeting Research Diagnostic Criteria for major depressive disorder and having a minimum pretreatment score of 22 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Patients were randomly assigned to placebo (2-10 capsules/day), imipramine (50-250 mg/day), or nefazodone in two dose ranges (50-250 mg/day or 100-500 mg/day). RESULTS: Improvement on depression measures with nefazodone in the 100-500-mg/day dose range (endpoint mean = 460 mg/day) and imipramine (endpoint mean = 214 mg/day) exceeded that with placebo. Some benefit was also observed in the nefazodone 50-250-mg/day treatment group (endpoint mean = 242 mg/day), but it was suboptimal. Evidence of nefazodone's efficacy as an antidepressant was consistently observed on physician- (HAM-D, Clinical Global Impressions [CGI]) and patient-rated (CGI-patient rated) scales. By patient self-report, improvement of anxiety symptoms associated with depression was evident with nefazodone as early as the first week of treatment, and benefit was seen with both nefazodone dosage groups. Analyses of the physician's global assessments of therapeutic effect and side effects at end of treatment showed therapeutic benefit for both nefazodone and imipramine treatments; however, patients in the nefazodone treatment groups were significantly less troubled by adverse experiences than were imipramine-treated patients, resulting in a lower dropout rate for adverse experience. CONCLUSION: Nefazodone is a well-tolerated and effective antidepressant for the treatment of major depressive disorder.

Comparative study of platelet 3H-paroxetine and 3H-imipramine binding in panic disorder patients and healthy controls.

High affinity 3H-paroxetine and 3H-imipramine binding sites were simultaneously studied in platelets of 29 untreated patients with panic disorder and 12 healthy controls. The maximum number of binding sites (Bmax) was found to be significantly lower in the panic patients compared to the controls using either ligand. No difference in the Kd values between the groups of subjects was found. The disturbance of serotonin neurotransmission in panic disorder--decrease in Bmax values--may be either a consequence or a reason of serotonergic dysfunction.

The dexamethasone suppression test in panic disorder and major depressive episodes.

Dexamethasone Suppression Tests (DST) were performed on 30 patients with panic disorder and on 30 patients treated for major depressive episodes in order to seek an answer to the question of whether or not the two disorders have a common biological background. The hypothesis was based on the results of family studies known from the literature and on the favorable therapeutic response obtained with tricyclic antidepressants. Normal suppressive (i.e., negative in our terminology) DSTs were found in 16.7% of the patients with panic disorder and in 56.7% of patients suffering from major depressive episodes. The anxiety indices of the two groups differed significantly from each other. The results do not suggest the possibility of a close genetic relationship between the two conditions.

[Relationship between schizophrenia, ABO system and secretory system (author's transl)]. / Relation entre schizophrénie, système ABO et système sécréteur.

The ABO blood groups and the secretor status of 210 schizophrenic patients born in Budapest and in her neighbourhood was determined by the author. According to principles of the nosological taxonomy suggested by Sneshnewski the patients were classified as three forms of process, continuous, shift-like and recurrent. It was found decrease of "O" antigen and increase of "A" antigen in the continuous form, while increase of "O" and decrease of "A" in the shift-like form. In the group showing recurrent form of process are genetically independent nosological units, it was found increase of "O" non-secretors. The various frequency of genes refer to biological origin and polygenic inheritance of the disease. The author emphasizes that genetic examination of schizophrenia should carry according to principles of nosology.