Patients with difficult-to-treat depression do not exhibit an increased frequency of CYP2D6 allele duplication.

The insufficient response of patients to antidepressant medications may result from several factors, including altered drug metabolism. CYP2D6 genotyping may help assess the possible factors that contribute to difficult-to-treat depression. The aim of our study was to determine the frequency of CYP2D6 allelic variants and the prevalence of predicted CYP2D6 phenotypes in patients who were suffering from difficult-to-treat depression and compare the data with those for the healthy population of Hungary.55 patients who failed to respond to 2 or more adequate trials of different CYP2D6-dependent antidepressants were selected for genotyping.The prevalence of the predicted CYP2D6 phenotypes in the patient population was 1.8% for the UMs, 80.0% for EMs, 3.6% for IMs and 14.5% for PMs compared with 1.9% for UMs, 83.3% for EMs, 6.5% for IMs and 8.3% for PMs in the Hungarian population.The CYP2D6 allele frequencies and the predicted phenotype distributions in patients with difficult-to-treat depression were not significantly different to those found in the healthy population of Hungary. The cumulative frequency of the CYP2D6*1XN, *2XN and *35XN alleles was 0.9% in the patient population -suggesting that CYP2D6 duplication or multiplication does not play a significant role in antidepressant pharmacotherapy failure in this patient sample. The cumulative frequency of the non-functional alleles (33.5%) and the prevalence of the genetically determined PM phenotype (14.5%) were relatively high in the patient group. These figures draw attention to the possibility of unrecognised and non-reported side effects and non-adherence to drug treatment.

Postoperative application of amphotericin B nasal spray in chronic rhinosinusitis with nasal polyposis, with a review of the antifungal therapy.

Chronic rhinosinusitis (CRS) affects 1-4% of the adult population. The etiology of this multifactorial, chronic disease, which leads to a significant impairment of the quality of life, often accompanied by nasal polyposis, is not fully understood. In the past decade, it was presumed that the disease, which causes characteristic eosinophilic infiltration of the nasal mucosa, is triggered by an enhanced (but not classical allergic IgE-type) immune response against fungal organisms in the nasal mucus. If this supposition is correct, then it appears obvious that the administration of amphotericin B nasal spray in adequate concentration following endoscopic polypectomy should be advantageous for these patients, and might even reduce the number of recurrent cases. To check on this assumption, we conducted a prospective randomized placebo-controlled trial involving 33 patients, 30 of whom remained in the study throughout. Patients with nasal polyposis were operated on with an endoscopic technique between 1 November 2005 and 1 October 2006; group A (14 randomly selected patients) were treated with a nasal spray containing 5 mg/ml amphotericin B, while the placebo group B (16 randomly selected patients) received a nasal spray lacking amphotericin B. We evaluated our results with the aid of a modified Lund-Mackay CT score, the SNAQ-11 test (which assesses changes in the symptoms), a quality of life test and endoscopy. The SPSS 14.0 for Windows program was utilized to process the data of examinations performed preoperatively and 1 year postoperatively. The CT scores of the group A patients 1 year after the operation exhibited wide scattering, without signs of recovery. The CT scores of the group B patients indicated a slight improvement, though this did not prove significant relative to group A. Both the SNAQ-11 test and the quality of life test revealed a significant improvement in each group, but the degrees of change in these tests did not differ significantly between the two groups of patients. The endoscopic findings indicated a slight improvement to the advantage of the amphotericin B-treated group 12 months after the operation. These results lead to the conclusion that the administration of amphotericin B nasal spray to patients operated on for nasal polyposis does not give rise to a significant alteration in either CT score, clinical symptoms, or quality of life. The more favorable clinical aspects observed in the amphotericin B-treated group during the endoscopic follow-up did not correspond to an improvement in the symptoms. In connection with the conclusions drawn from this study, the authors discuss the controversial data available on the fungal etiology of CRS. They critically analyze the contradictory observations and conclusions of seven recent clinical studies.

Investigation of abiogenic stress-induced alterations in the level of secondary metabolites in poppy plants (Papaver somniferum L.).

We aimed to understand the effects of water stress on the alkaloid production in various developmental stages of poppy plants and the effect of stress on the alkaloids content in the capsules. Three stages of the life cycle of Papaver somniferum L. were selected in our studies: Rosette, Flowering and Lancing developmental stages. Four types of water conditions were examined: Control, Withdrawal of Water, 50% Water Supply and Inundation. The morphological monitoring, results of Relative Water Content and proline content were used as indicators of stress. The result of the measurements in poppy leaves show that the secondary metabolites dramatically respond to these stress conditions. The constant water supply was beneficial for the accumulation of alkaloids in the capsules.

Thin-layer chromatography-densitometry and liquid chromatography analysis of alkaloids in leaves of Papaver somniferum under stress conditions.

The effect of stress conditions on the concentrations of secondary metabolites were examined during various developmental stages of Papaver somniferum plants. P. somniferum plants were grown in laboratory conditions (Budakalász). The experiment consisted of 22 treatments. Significantly different alkaloid contents can be observed under different stress conditions. In general, the alkaloid contents of plants are very low; therefore, a highly sensitive and reliable method has to be developed for analysis. The amount of alkaloids was measured by 2 separation and detection techniques. Accuracy of the thin-layer chromatography method for quantitative analysis is limited. Without purification of samples the background is too noisy. Column liquid chromatography is a sensitive and relatively inexpensive method that allows precise quantitative determination of the alkaloid content.

[Chemical tests with Marrubium species. Official data on Marubii herba in Pharmacopoeia Hungarica VII]. / Marrubium fajok növénykémiai vizsgálata Adatok a VII. Magyar Gyógyszerkönyv Marrubii herba cikkelyéhez.

About 40 species of the Marrubium genus (Lamiaceae) are known of which 2 species (M. vulgare L. and M. peregrinum L.) and one hybrid (M. x paniculatum Desr.) can be found as native plants in Hungary. The above-ground parts of M. vulgare L. are official in Hungarian Pharmacopoeia VII. Active substances in Marrubii herba are labdane-structured bitter materials. Although the presence of furanic labdane diterpenes in the plant is known, the pharmacopoeia gives only microscopic tests, qualitative tests (for other parts of the plant and foreign organic matter) for the bitter value of Marrubii herba. We have examined the main terpenoid substances isolated with column, gel and preparative layer chromatography. Structure elucidations were performed by means of UV, mass and NMR spectroscopy. We have compared the changes in terpenoid-type compounds (premarrubiin and marrubiin) in plants during the vegetation period; in different Marrubium species and in the different extractions of horehound by means of thin layer chromatography and densitometry. By reason of our results we propose qualitative and quantitative chemical tests for the paragraph of Marrubii herba in Pharmacopoeia Hungarica VII.

Comparsion of hydroxyindole-O-methyltransferse levels in pineal glands of normal, blinded, and congenitally anophthalmic guiena pigs.

The level of pineal hydroxyindole-O-methyltransferase activity was measured in normal sighted, normal blinded, and congenitally anophthalmic guinea pigs at 1100-1200 and 2300-2400 h. Significant day-night differences were found in the normal sighted and normal blinded guinea pigs; however, the levels were markedly elevated in the normal blinded guinea pigs. The congenitally anophthalmic guinea pigs did not demonstrate a difference between day and night activities. Both the day and night levels of hydroxyindole-O-methyltransferase activities in the latter animals were slightly less than the low daytime levels for the normal, sighted guinea pigs.