Pharmacopoieal quality of non-expired and expired nifedipine formulations from Estonian and Russian Federation medicinal products market.

The pharmacopoeial quality of non-expired and expired nifedipine tablets of the same batches purchased from the Estonian and Russian Federation medicinal product markets was evaluated. The IR spectroscopy, HPLC analysis for quantitative content and purity of the active pharmaceutical ingredient (API), and dissolution test techniques were applied. In the experiments with non-expired nifedipine tablets, in all Estonian (n = 8, label claims 10, 20, and 40 mg) and Russian Federation (n = 4, label claim 10 mg) registered formulations the API was identified and quantified as nifedipine in amounts set by the European Pharmacopoeia and without exceeding the tolerance limits for the impurities. The dissolution rate was variable but all 10 and 20 mg non-expired nifedipine tablets released at least 80% of API in 12 h. The expiration of the nifedipine tablets led to somewhat increased dissolution rate while only traces of the nifedipine degradation products were discovered in the dissolution medium. In conclusion, our present study shows that with minor variations the Estonian and Russian Federation registered nifedipine tablets are comparable, the API preserves well beyond the expiration date but the expired nifedipine tablets may release the API faster than the non-expired tablets.

Phenolic compounds in five Epilobium species collected from Estonia.

Epilobium species have been traditionally used as medicinal plants to treat benign prostate hyperplasia. The present study investigated the content of polyphenols, tannins, and flavonoids in Epilobium parviflorum Schreb., E. hirsutum L., E. adenocaulon Hausskn., E. montanum L., and E. palustre L. growing in Estonia. The total contents of polyphenols, tannins, and flavonoids were studied using UV spectroscopy with subsequent HPLC quantification of gallic acid, ellagic acid, and quercetin as marker compounds. All roots, stems, leaves, and flowers of the plants investigated contained comparable amounts of polyphenols, tannins, and flavonoids. There was a clear positive correlation between the contents of tannins and flavonoids in various plant parts. The content of these biologically active compounds suggests the use of E. parviflorum, E. hirsutum, E. adenocaulon, E. montanum, and E. palustre collected from Estonia as herbs both individually or as a blend.

Inorganic ions in the medium modify tropane alkaloids and riboflavin output in Hyoscyamus niger root cultures.

CONTEXT: Hyoscyamus niger L. (Solanaceae) roots are rich of tropane alkaloids, such as hyoscyamine and scopolamine are used as the source of raw material for the pharmaceutical industry. AIMS: The aim of the present study was to investigate the effect of calcium, magnesium, and iron ions on the production of tropane alkaloids and excretion of riboflavin in H. niger root cultures. MATERIALS AND METHODS: The calcium, magnesium, or iron enriched/deprived Murashige and Skoog (MS) growth medium were used for culture of H. niger root tissues. The secondary metabolites were quantified using high performance liquid chromatography with ultraviolet detector (HPLC-UV) and fluorimetry techniques. RESULTS: An increased calcium content in the medium unidirectionally reduced hyoscyamine, while increasing scopolamine production with only a moderate impact on riboflavin excretion. Manipulations with magnesium and iron contents in the medium resulted in divergent changes in hyoscyamine, scopolamine, and riboflavin concentrations. CONCLUSIONS: Our results show that increased calcium ion content in the Murashige and Skoog medium may be used for the intensification of the scopolamine production in H. niger root cultures.

Vegetational variation of phenolic compounds in Epilobium angustifolium.

Epilobium angustifolium L. herbs are used in ethnomedicine to treat benign prostate hyperplasia. The aim of the study was to investigate the phenolic contents in distinct E. angustifolium organs during the whole vegetational period from May to October. The plants were obtained from a remote habitat in Estonia and spectrophotometrically analysed for the total polyphenol, tannin, and flavonoid contents. The total polyphenol content was the highest in roots (85 mg g(-1)) and stems (67 mg g(-1)) in July. The total flavonoid content was the highest in leaves (2.36 mg g(-1)) and flowers (2.09 mg g(-1)) and it remained relatively stable during the summer months. The highest tannin content was found in small growing plants in May; in older ones it declined, whereas the absolute yield per plant was greater. In sum, the aerial organs without stems collected in July-August are the best choice to get E. angustifolium plant material with stable high phenolic content.

Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin.

Valproic acid (VLP) is a widely used anticonvulsant and mood-stabilizing drug that relieves the endoplasmic reticulum (ER) stress response, a pathogenetic process related to diabetes. The aim of the present study was to evaluate whether acute valproic acid is able to interfere with glucose intolerance in two different diabetes models: The first model was a Wfs1 mutant mouse with an elevated ER stress response and the second model a streptozocin-induced diabetic mouse. VLP (300 mg/kg, i.p.) was administered to Wfs1 knockout (KO) mice and glucose tolerance test was performed 15 min later. VLP did not have an effect on the course of the glucose tolerance test in wild-type mice, while it did normalize the glucose intolerance in Wfs1 knockout mice. Acute valproic acid also lowered the blood glucose levels in streptozocin-treated mice and potentiated the effect of insulin in these mice. Thus, acute valproic acid is effective in lowering blood glucose levels possibly by potentiating insulin action in both Wfs1 KO mice and in streptozocin-induced type 1 diabetic mice.

Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge

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Loss of function of the Wfs1 gene causes Wolfram syndrome, a rare multisystem degenerative disorder. Mutant mice with targeted Wfs1 gene disruption (Wfs1 KO) display morphological and behavioral impairments that are not well understood. The present study aimed to investigate the striatal dopamine output of wild-type, heterozygous, and homozygous Wfs1 null-mutant mice using in vivo microdialysis technique. The baseline dopamine output in striatum was similar in all three animal groups. The application of 100 mM [K+]-rich modified Ringer solution caused in homozygous Wfs1 mutant mice an increase of dopamine output by 400%, while in wild-type and heterozygous animals, the increase of the dopamine output yielded up to 1,200%. In sum, the homozygous Wfs1 mutant (..) (AU)

Lower anxiety and a decrease in agonistic behaviour in Lsamp-deficient mice.

In rodents, the Lsamp gene has been implicated in trait anxiety, fear reaction and fear conditioning. Human data link the LSAMP gene to several psychiatric disorders. In this study, we presented a general phenotypic characterization of Lsamp gene-deficient mouse line, created by deleting exon 1b. These mice displayed no gross sensory-motor deficiencies, no overt abnormalities and performed normally in memory and learning tests. However, they responded with increased activity to new environments. Moreover, they displayed reduced anxiety and notable deviations in social behaviour, such as lack of whisker trimming, reduced aggressiveness and reduced dominance. One possible explanation for the anxiolytic-like effect of the deletion of the Lsamp gene is a shift in balance in the Gabra1 and Gabra2 genes in the temporal lobe in favor of the Gabra2 transcript, encoding α2 subunit of GABA(A) receptors that mediate the stimulating effect of GABA agonists. The overall phenotype of Lsamp-deficient mice, characterized by decreased anxiety and several alterations in social behaviour, makes them a good model for studying the molecular mechanisms behind inadequate social behaviours observed in several psychiatric disorders.

Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge.

Loss of function of the Wfs1 gene causes Wolfram syndrome, a rare multisystem degenerative disorder. Mutant mice with targeted Wfs1 gene disruption (Wfs1 KO) display morphological and behavioral impairments that are not well understood. The present study aimed to investigate the striatal dopamine output of wild-type, heterozygous, and homozygous Wfs1 null-mutant mice using in vivo microdialysis technique. The baseline dopamine output in striatum was similar in all three animal groups. The application of 100 mM [K+]-rich modified Ringer solution caused in homozygous Wfs1 mutant mice an increase of dopamine output by 400%, while in wild-type and heterozygous animals, the increase of the dopamine output yielded up to 1,200%. In sum, the homozygous Wfs1 mutant mice (AUC0₋3 = 0.212 nM/µl h) show significantly decreased striatal dopamine output in response to high-concentration [K+] challenge as compared with wild-type or heterozygous Wfs1 mutant conspecifics (AUC0₋3 = 0.427 and 0.505 nM/µl h, respectively). This could explain at least some of the behavioral alterations in Wfs1 mutant mice.

Lead content in pot marigold (Calendula officinalis L.) inflorescences and leaves: impact of precipitations and vicinity of motorway.

Trace metal contamination is a major environmental and health problem virtually in all countries. The present study was aimed to estimate the lead content of pot marigold (Calendula officinalis L.) inflorescences and leaves collected from a nonpolluted test field. The lead content in dry pot marigold inflorescences was 9.34 ± 0.79 µg/g, in dry leaves 11.57 ± 0.47 µg/g, and in soil 0.649 ± 0.012 µg/g. The distance of pot marigold collection beds (30-220 m from the motorway) had no effect on lead content. There was a strong positive correlation between the amount of precipitations and lead content of pot marigold leaves but not inflorescences indicating the soil as primarily the source of increased lead content. In conclusion, no effect of motorway vicinity was found for pot marigold inflorescences or leaves lead content; however, as a precaution, it is not recommended to collect the plants during or just after showers.

Higher plasma ACTH levels in adults with Asperger syndrome.

OBJECTIVE: The aim of this preliminary study was to characterize the levels of plasma adrenocorticotropic hormone (ACTH) and cortisol in adult patients with Asperger syndrome (AS). METHODS: Twenty medication-free individuals with high-functioning AS were recruited from a clinic specialized in autism spectrum disorders. Ten age-matched healthy persons (hospital staff or students) with no neuropsychiatric disorders served as controls. Blood samples for the assessment were collected at 8:00 a.m. RESULTS: The patients with AS had significantly higher plasma-ACTH values than did the healthy controls. Plasma-cortisol levels were similar in both groups. CONCLUSION: Increased plasma-ACTH levels are associated with AS. Future studies are needed to clarify whether this finding is a biological consequence of chronic anxiety and elevated stress, or a sign of facilitated response to an acute novel stressor.

Role of 5-HT1A receptors in the mediation of acute citalopram effects: a 8-OH-DPAT challenge study.

(1) The study was aimed to investigate the effects of the minimal effective doses of acute citalopram (5 mg/kg), (+/-)-8-hydroxydipropylaminotetralin HBr (8-OH-DPAT; 0.1 mg/kg), and their combined treatment on the rat open field and forced swimming behaviour and post-mortem monoamine content. (2) The animals were prospectively divided into the vehicle- and para-chlorophenylalanine (p-CPA)-pretreated (350 mg/kg) groups. (3) Acute citalopram (5 mg/kg), 8-OH-DPAT (0.1 mg/kg), or their combined treatment had no major effect on the rat open field and forced swimming behaviour. (4) The post-mortem catecholamine content in four brain regions studied was unchanged in all treatment groups. (5) The combined 8-OH-DPAT (0.1 mg/kg) and citalopram (5 mg/kg) treatment partially reversed the p-CPA-induced decrease of serotonin (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) content. (6) The present experiments demonstrate that the 5-HT1A receptors mediate some of the selective serotonin reuptake inhibitor (SSRI)-induced biochemical phenomena.