Caraway (Carum carvi L.): Anther Culture and Production of DH Plants Caraway.

We describe the production of doubled haploids through anther culture in caraway. Induction conditions for the cultivation of donor plants, anther collection, composition of culture media, and physical induction conditions for embryogenesis have been described. As a result, responsive lines with numerous haploid embryo production were obtained, which after colchicine treatment became fertile. From a practical point of view, two doubled haploid populations are tested under field conditions.

Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-study on P300 and mismatch negativity in healthy volunteers.

RATIONALE: Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors in information processing is less clear. OBJECTIVES: We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/C agonistic properties, in healthy volunteers. METHODS: Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed. RESULTS: Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude (p = 0.009) but did not affect the MMN. Psilocybin's disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude (p = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude (p = 0.014). CONCLUSIONS: Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT2A receptors in altered information processing in psychosis and schizophrenia.

Role of Glutamatergic System in Obsessive-Compulsive Disorder with Possible Therapeutic Implications.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric illness and 1 of the most common anxiety disorders with the prevalence of 3%. Although its pathogenesis remains unclear, the traditional model focused on alternations in the serotonin system. Selective serotonin reuptake inhibitors provide the most effective treatment; however, as much as 40-60% of patients do not respond to antidepressants therapy. Thus, attention has shifted towards other neurotransmitter systems and related neuroanatomical structures. Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis. In this review, we link together the existent neuroanatomical, neurophysiological, and neuropsychological evidence to argue for potential benefits of adjuvant treatment with glutamatergic agents, especially memantine. By a targeted de-excitation effect on the glutamatergic system in the temporal lobes and connected brain regions, memantine might further alleviate OCD symptoms. This effect should be even more pronounced in certain subtypes of patients with specific cognitive deficits and maladaptive compensatory memory processes (e.g., checkers).

Parathyroidectomy in Hyperparathyroidism-Associated Calciphylaxis in End-Stage Renal Disease Should be Prompt and Radical - a Case Report with Two Original Therapeutic Modifications and Successful Outcome.

We present a case of severe calciphylaxis in both thighs and calves in a patient with end-stage renal disease and advanced secondary hyperparathyroidism with successful outcome after modified therapeutic approach. The cause of calciphylaxis is multifactorial. In our case, not only severe hyperparathyroidism and mediocalcinosis, but also medication (warfarin, calcium and active vitamin D) was involved. Because the initial conservative therapy was not successful, we indicated parathyroidectomy. However, we were not able to localize parathyroid glands and we contraindicated bilateral neck exploration due to the patient's critical status. Therefore, we decided for total thyroidectomy with total parathyroidectomy. Surgery was uncomplicated and histology confirmed that all four parathyroid glands were removed. The expected post-operative hypocalcaemia was asymptomatic and we did not use any calcium supplementation or vitamin D. Thyroid hormone replacement was easy. After surgery, the large and multiple subcutaneous defects started to heal. We achieved complete healing within several months of continuing dedicated care. There is no recurrence after three years. Prompt and radical surgical parathyroidectomy was extremely useful in our patient.

Endocannabinoid system in sexual motivational processes: Is it a novel therapeutic horizon?

The endocannabinoid system (ECS), which is composed of the cannabinoid receptors types 1 and 2 (CB1 and CB2) for marijuana's psychoactive ingredient Δ9-tetrahydrocannabinol (Δ9-THC), the endogenous ligands (AEA and 2-AG) and the enzymatic systems involved in their biosynthesis and degradation, recently emerged as important modulator of emotional and non-emotional behaviors. For centuries, in addition to its recreational actions, several contradictory claims regarding the effects of Cannabis use in sexual functioning and behavior (e.g. aphrodisiac vs anti-aphrodisiac) of both sexes have been accumulated. The identification of Δ9-THC and later on, the discovery of the ECS have opened a potential therapeutic target for sexual dysfunctions, given the partial efficacy of current pharmacological treatment. In agreement with the bidirectional modulation induced by cannabinoids on several behavioral responses, the endogenous cannabinoid AEA elicited biphasic effects on sexual behavior as well. The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of several aspects of sexuality in preclinical and human studies, highlighting their therapeutic potential.

Low-dose cholecalciferol supplementation and dual vitamin D therapy in haemodialysis patients.

BACKGROUND: Traditionally, secondary hyperparathyroidism (SHPT) due to low calcitriol synthesis in failing kidneys has been treated with synthetic vitamin D receptor (VDR) activators. Recently, also the importance of low native vitamin D status beyond the issue of SHPT has been recognized in these patients. The aim of this work was to evaluate the effect of cholecalciferol supplementation in haemodialysis patients with low vitamin D serum levels. Another aim was to evaluate dual vitamin D therapy (cholecalciferol supplementation plus paricalcitol) in haemodialysis patients with vitamin D deficiency and concomitant SHPT. METHODS: Ninety clinically stable maintenance haemodialysis patients were included. Supervised cholecalciferol supplementation was administered due to low vitamin D status. Patients with SHPT were also treated with synthetic VDR activator. Two pre hoc subgroups for statistical analysis were formed: patients treated solely with cholecalciferol (N=34; 5,000 IU once weekly) and patients treated with a combination of cholecalciferol (identical dose, i.e. 5,000 IU/week) plus paricalcitol (N=34, median dose 10 µg/week). Follow-up visit was scheduled 15 weeks later. Serum concentrations of calcidiol (25-D), parathyroid hormone (PTH) and beta-cross laps (CTX) were assessed at baseline and at follow-up. Serum calcium, phosphate and alkaline phosphatase (ALP) were monitored monthly. Only non-calcium gastrointestinal phosphate binders were administered. Dialysate calcium was 1.5 mmol/L in all patients, and no oral calcium-containing preparations were prescribed. Depending on data distribution, parametric or nonparametric statistical methods were used for comparison within each group (i.e. baseline vs. follow-up data) as well as between groups. RESULTS: In the whole group of 90 patients, mean baseline 25-D serum level was 20.3 (standard deviation 8.7) nmol/L, and it increased to 66.8 (19) nmol/L (p<0.0001) after supplementation. In both preformed subgroups, the effect of vitamin D supplementation was almost identical. In cholecalciferol monotherapy, 25-D levels increased from 18.4 (8.2) to 68.6 (21.2) and in dual vitamin D therapy from 18.4 (5.0) to 67.6 (17.7) nmol/L (both p<0.0001). In addition, both treatment modalities decreased serum PTH levels importantly: from 21.7 (interquartile range 17.3; 35.4) to 18.1 pmol/L (15.3; 24.7) in monotherapy (p=0.05) and from 38.6 (31.8; 53.3) to 33.9 pmol/L (26.1; 47.5) in dual vitamin D therapy (p=0.01). Serum calcium, phosphate, ALP and CTX did not change. We have not observed any episode of hypercalcemia in any subject during the whole period of follow-up. At baseline, slightly lower 25-D levels were observed in diabetic than in non-diabetic patients. This difference disappeared after substitution. Vitamin D status and its changes were not related to the patient's age. CONCLUSION: Low 25-D levels were very common in haemodialysis patients. They were safely and effectively corrected with supervised low-dose cholecalciferol supplementation. In patients with higher baseline PTH levels, dual vitamin D therapy (cholecalciferol plus paricalcitol) was safely and effectively used.

Prediction of treatment response and the effect of independent component neurofeedback in obsessive-compulsive disorder: a randomized, sham-controlled, double-blind study.

AIMS: The goal of this study was to assess the effect of independent component neurofeedback (NFB) on EEG and clinical symptoms in patients with obsessive-compulsive disorder (OCD). Subsequently, we explored predictors of treatment response and EEG correlates of clinical symptoms. METHODS: In a randomized, double-blind, parallel design, 20 inpatients with OCD underwent 25 sessions of NFB or sham feedback (SFB). NFB aimed at reducing EEG activity in an independent component previously reported abnormal in this diagnosis. Resting-state EEG recorded before and after the treatment was analyzed to assess its posttreatment changes, relationships with clinical symptoms and treatment response. RESULTS: Overall, clinical improvement in OCD patients was not accompanied by EEG change as assessed by standardized low-resolution electromagnetic tomography and normative independent component analysis. Pre- to posttreatment comparison of the trained component and frequency did not yield significant results; however, in the NFB group, the nominal values at the downtrained frequency were lower after treatment. The NFB group showed significantly higher percentage reduction of compulsions compared to the SFB group (p = 0.015). Pretreatment higher amount of delta (1-6 Hz) and low alpha oscillations as well as a lower amount of high beta activity predicted a worse treatment outcome. Source localization of these delta and high beta oscillations corresponded with previous EEG resting-state findings in OCD patients compared to healthy controls. CONCLUSION: Independent component NFB in OCD proved useful in percentage improvement of compulsions. Based on our correlation analyses, we hypothesize that we targeted a network related to treatment resistance.

Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: voxel-based-morphometry (VBM) study.

OBJECTIVES: To address the role of latent T. gondii infection in schizophrenia we studied the influence of latent toxoplasmosis on brain morphology. METHODS: An optimized voxel-based morphometry of magnetic resonance imaging was analyzed by analysis of variance with diagnosis and seropositivity as factors in 44 schizophrenic patients (12 T. gondii positive) and 56 controls (13 T. gondii positive). RESULTS: Grey matter (GM) volume was reduced in schizophrenia patients compared with controls in the cortical regions, hippocampus and in the caudate. In the schizophrenia sample we found a significant reduction of GM volume in T. gondii positive comparing with T. gondii-negative patients bilaterally in the caudate, median cingulate, thalamus and occipital cortex and in the left cerebellar hemispheres. T. gondii-positive and -negative controls did not differ in any cluster. Among participants seropositive to T. gondii the reduction of GM in the schizophrenia subjects was located in the same regions when comparing the entire sample (11,660 over-threshold voxels (P ≤ 0.05, FWR corrected). The differences between T. gondii-negative patients and controls consisted only of 289 voxels in temporal regions. CONCLUSIONS: Our study is the first to document that latent toxoplasmosis reduces GM in schizophrenia but not in controls.

Electroencephalographic spectral and coherence analysis of ketamine in rats: correlation with behavioral effects and pharmacokinetics.

AIMS: This study was designed to evaluate the changes in EEG power spectra and EEG coherence in a ketamine model of psychosis in rats. Analyses of behavioral measurements--locomotion and sensorimotor gating--and the pharmacokinetics of ketamine and norketamine were also conducted. METHODS: Ketamine and norketamine levels in rat sera and brains were analyzed by gas chromatography-mass spectrometry after ketamine 30 mg/kg (i.p.). Ketamine 9 and 30 mg/kg (i.p.) were used in the behavioral and EEG experiments. Locomotor effects in an open field test and deficits in prepulse inhibition of acoustic startle reaction (PPI ASR) were evaluated in the behavioral experiments. EEG signals were simultaneously recorded from 12 implanted active electrodes; subsequently, an EEG power spectral and coherence analysis was performed. RESULTS: Ketamine had a rapid penetration into the brain; the peak concentrations of the drug were reached within 15 min after administration. Ketamine induced marked hyperlocomotion and deficits in the PPI ASR. EEG spectral analysis mainly showed increases in EEG power as well as coherence. These were most robust at 10-15 min after the administration and influenced all parts of the spectrum with ketamine 30 mg/kg. CONCLUSIONS: Ketamine at behaviorally active doses induces a robust increase in EEG power spectra and coherence. The maximum levels of change correlated with the kinetics of ketamine.

Primary hyperparathyroidism associated with hypocalcemia in a patient presenting with kidney disease.

Elevated serum parathyroid hormone (PTH) level together with hypocalcemia in chronic kidney disease usually suggests secondary hyperparathyroidism. However, primary hyperparathyroidism should also be considered, especially if concomitant vitamin D deficiency is suspected. We report a case of parathyroid adenoma associated with hypocalcemia and metabolic bone disease in a patient presenting with kidney disorder. The patient was successfully treated by parathyroidectomy that was preceded and followed by intensive calcium and vitamin D supplementation.

The effect of a full agonist/antagonist of the D1 receptor on locomotor activity, sensorimotor gating and cognitive function in dizocilpine-treated rats.

Cognitive impairment has been found across all subtypes of schizophrenia. The location and function of dopamine-1 receptors (D1Rs) make them attractive targets for the treatment of cognitive impairment in schizophrenia. Here we investigate the systemic effect of a D1R agonist (A77636) and antagonist (SCH 23390) on hyperlocomotor activity and cognitive deficit induced by an NMDA receptor antagonist (MK-801). Wistar rats (250-300 g) received A77636 (0.1, 0.5 or 1 mg/kg) or SCH 23390 (0.02 or 0.05 mg/kg) with MK-801 (0.1 mg/kg) or saline for 4 d. On day 4 we assessed the prepulse inhibition of the acoustic startle response, locomotor activity in a novel arena and active allothetic place avoidance (spatial memory task) 15 min after the last injection. Systematic administration of the D1R agonist at 0.1 mg/kg ameliorates cognitive dysfunction in our model of schizophrenia, but increases stereotypy and locomotor activity (model of psychotic symptoms) at higher doses (0.5 or 1 mg/kg). Administration of the D1R antagonist had no effect on cognitive function, but decreased hyperlocomotion induced by MK-801. Thus, based on our results, over-activation of D1Rs may exacerbate psychotic symptoms in patients with schizophrenia.

The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801.

The purpose of the present study was to investigate the opposite effect of the pre- and postsynaptic serotonin-1A (5-HT(1A)) receptors on the psychotic-like behavior induced by a non-competitive antagonist of the NMDA receptor, dizocilpine (MK-801). Male Wistar rats received two doses (0.025mg/kg and 1mg/kg) of 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin) and/or MK-801 in two different doses, 0.1mg/kg or 0.3mg/kg. We measured sensorimotor gating by testing prepulse inhibition of acoustic startle response (PPI) and locomotor activity of rats. We found an opposite effect of the low and high 5-HT(1A) receptor agonist doses on MK-801 induced deficit in PPI and hyperlocomotion in habituated rats. The low dose of 8-OH-DPAT, which preferentially acts on presynaptic 5-HT(1A) receptors, restored the deficit in PPI and hyperlocomotion in MK-801 (0.1mg/kg)-treated habituated rats. However, the high dose of 8-OH-DPAT, which activates both pre- and postsynaptic 5-HT(1A) receptors, decreased PPI and increased locomotor activity after administration of the low dose of MK-801. Administration of 8-OH-DPAT itself dose-dependently decreased PPI. However, only the high dose of 8-OH-DPAT increased spontaneous locomotor activity of rats. Our results indicate that there is an interaction between the NMDA and 5-HT(1A) receptors. In addition, these findings could indicate that activation of the 5-HT(1A) autoreceptor could be effective as a treatment in schizophrenia, but full potent agonism of the receptor could worsen the psychotic symptoms.

The effect of repetitive transcranial magnetic stimulation (rTMS) on symptoms in obsessive compulsive disorder. A randomized, double blind, sham controlled study.

BACKGROUND: The goal of our study is to assess whether transcranial magnetic stimulation (rTMS) would facilitate the effect of antidepressant in OCD patients. METHOD: The aim of the randomized, double-blind, sham controlled study was to compare the 2 and 4 week efficacy of the 10 sessions rTMS with sham rTMS in serotonin reuptake inhibitor resistant OCD patient. Thirty three right-handed patients were randomly assigned to either active rTMS or to sham rTMS. Active rTMS with the frequency of 1 Hz at 110% of motor threshold (MT) was administered over the left dorso-lateral prefrontal cortex. The same time schedule was used for sham administration. Thirty patients finished the study, three patients' dropped out at the beginning. Psychopathology was assessed by CGI, HAMA, Y-BOCS and BAI before the treatment, immediately after the experimental treatment, and 2 weeks after the experimental treatment by an independent reviewer. RESULTS: Both groups improved during the study period but the treatment effect did not differ between them in any of the instruments. CONCLUSION: Low frequency rTMS administered over the left dorso-lateral prefrontal cortex during 10 daily sessions did not differ from sham rTMS in facilitating the effect of serotonin reuptake inhibitors in OCD patients.

The effect of zotepine, risperidone, clozapine and olanzapine on MK-801-disrupted sensorimotor gating.

Dizocilpine (MK-801; 0.3 mg/kg i.p.)-induced disruption in prepulse inhibition of the acoustic startle response (PPI) can be preferentially restored by "atypical" antipsychotics. In contrast, some findings indicate that not all of the "atypical" antipsychotics, such as clozapine and risperidone, are effective in restoring the NMDA antagonist-induced deficits in PPI. In our study, we evaluated the effect of four different "atypical" antipsychotic drugs on deficits in PPI induced by MK-801. Zotepine and risperidone have high affinities to D2-like and 5-HT2A receptors, while clozapine and olanzapine have multipharmacological profiles with the highest affinities to serotonin 5-HT1A,2A/2C receptors and muscarinic receptors. Results have shown that MK-801 disrupted PPI and increased the ASR in rats. Our results showed no effect of zotepine (1 and 2 mg/kg) and risperidone (0.1 and 1 mg/kg) on disrupted PPI by MK-801. Administration of clozapine (5 and 10 mg/kg) and olanzapine (2.5 and 5 mg/kg) restored the deficits in PPI induced by MK-801. Additionally, we found a decrease of approximately 46% in PPI after administration of clozapine (5 mg/kg) and olanzapine (2.5 and 5 mg/kg) without MK-801 treatment. In summary, the four "atypical" antipsychotics had different efficacies to restore the disrupted PPI by MK-801. Only clozapine and olanzapin restored the MK-801-induced deficits in PPI.

Bright light therapy and/or imipramine for inpatients with recurrent non-seasonal depression.

INTRODUCTION: The aim of a double-blind study was to assess the efficacy of bright light therapy and/or imipramine in the treatment of inpatients suffering with recurrent non-seasonal major depressive disorder. METHOD: 34 in-patients with DSM-III-R diagnosis of major depressive disorder, recurrent type, were randomly allocated into 3 treatment groups. After 4-day washout period with baseline assessment they underwent 3 weeks of different types of treatment: a) Group A: bright light therapy (5000 lux from 6-8 a.m.) and imipramine 150 mg/day. b) Group B: bright light therapy (5000 lux from 6-8 a.m.) and imipramine-like placebo. c) Group C: dim red light (500 lux from 6-8 a.m.) and imipramine 150 mg/day. Outcome measures included weekly Hamilton Psychiatric Rating Scale for Depression, Clinical Global Impression Scale, Montgomery and Asberg Psychiatric Rating Scale for Depression and Beck Depression Inventory. RESULTS: Patients of all three groups improved significantly. The improvement of the patients of group B treated with bright light therapy plus placebo was superior to the other two groups, but not significantly. CONCLUSION: Bright light therapy can be effective in the treatment of non-seasonal major depressive disorder.