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Biomedical subjects

B Ahrens

Publications and source records attributed to B Ahrens.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects.

BACKGROUND: A robust association between "suicidality" and deficits of the serotoninergic neurotransmission has been claimed in the past. However, many studies having investigated the relationship between suicidality and peripheral indicators of serotoninergic neurotransmission suffer from considering only one or a very small number of potentially useful serotoninergic parameters, whereas a synoptic multidimensional approach appears to be more appropriate. Furthermore, the psychiatric context within which suicidal behaviour occurs should be considered when interpreting biochemical findings of patients with suicidal ideation and suicide attempts. METHODS: In the present study 5 peripheral serotonergic markers, (platelet 5HT concentration, 5HT uptake activity, 5HT(2A) receptor binding characteristics, MAO-B activity and tryptophan concentration in plasma) were assessed simultaneously. Of the 60 acutely suicidal inpatients (ICD-10: F43.xx, n = 52; F31/32/33, n = 8), 45 were suicide attempters. Data of 28 nonsuicidal patients with major depression (F31, n = 4; F32, n = 14; F33, n = 10) and 123 healthy volunteers represented the control groups. RESULTS: Mean platelet 5HT concentration was significantly lower in suicidal inpatients when compared to nonsuicidal depressed patients, but did not differ from the figure in healthy subjects. Nonsuicidal depressed patients showed significantly higher mean platelet-5HT concentration than healthy controls. Mean V(max) of 5HT uptake in washed platelets, but not in platelet-rich plasma, was significantly higher in suicidal patients than in healthy controls, not, however, when compared to nonsuicidal depressed patients. Mean K(D) for the platelet 5HT(2A) receptor and MAO-B activity were significantly lower in suicidal patients as compared to nonsuicidal depressed patients and healthy controls. The observed differences in peripheral serotonergic markers between groups are partially due to a significant gender effect. A lower MAO-B activity was observed only in suicidal females, while the higher V(max) of 5HT uptake in washed platelets of suicidal patients was due to suicidal males. CONCLUSIONS: In view of conflicting observations made by other authors and the present findings on suicidal patients with adjustment disorder it remains doubtful whether and if so to which extent platelet studies can provide valid information on serotonergic mechanisms related to suicidal behaviour.

Adult↗
PubMed2006

Gene expression profiling as novel tool in experimental asthma research.

With the advances achieved in decoding of the genetic structures of species and the novel possibilities of simultaneous measurements of the regulation of all genes of a given tissue, the last 10 years have seen a massive increase of our knowledge about genetic regulation of diseases. Additionally, the possibilities to control transcriptional processes within the cells will speed up the process of disentangling the various pathways leading to disease.

Animals↗
PubMed2006

Allergic lung inflammation induces pulmonary vascular hyperresponsiveness.

Pulmonary arterial vasoconstriction is an important early component of pulmonary hypertension. Inflammatory mechanisms play a prominent role in the pathogenesis of pulmonary hypertension. The present authors investigated the potential role of acute allergic lung inflammation for alterations in pulmonary haemodynamics. BALB/c mice were intraperitoneally sensitised to ovalbumin and challenged by ovalbumin inhalation. Subsequently, lungs were ventilated and perfused ex vivo, and pulmonary arterial pressure (P(pa)) was continuously monitored. Isolated perfused lungs of allergen-sensitised and -challenged mice showed five-fold enhanced P(pa) responses to serotonin, which is reported to be a significant contributor to pulmonary hypertension in humans. This increase in P(pa) was abolished by the serotonin receptor-2A antagonist ketanserin, but not the serotonin receptor-1B antagonist GR127935. Intracellular signalling to serotonin involved phosphatidylcholine-specific phospholipase C and protein kinase C, as well as Rho-kinase, as assessed by employing the specific inhibitors D609, bisindolylmaleimide and Y27632, respectively. In addition to serotonin, impressively enhanced P(pa) increases in allergic lungs were also evoked by the thromboxane receptor agonist U46619, angiotensin II and endothelin-1. In conclusion, allergic lung inflammation was accompanied by impressive pulmonary vascular hyperresponsiveness. These results suggest a possible role for allergic inflammation in the development of pulmonary arterial hypertension.

Animals↗
PubMed2006

Common vaccine antigens inhibit allergen-induced sensitization and airway hyperresponsiveness in a murine model.

BACKGROUND: Co-vaccination with cellular pertussis vaccine down-regulates allergic sensitization to diphtheria and tetanus antigens. Using a murine model, we investigated whether vaccination with diphtheria/tetanus toxoids, administered separately or simultaneously with the whole cell vaccine of Bordetella pertussis, inhibits subsequent allergen-induced immune and inflammatory responses. METHODS: BALB/c-mice were vaccinated intracutaneously with a combination of diphtheria and tetanus toxoids or a combination of diphtheria and tetanus toxoids with a whole cell vaccine of B. pertussis (three times, days -21 to -7) prior to systemic sensitization (days 1-14) and repeated airway challenges (days 28-30) with ovalbumin. RESULTS: Compared with negative controls, systemic sensitization and airway allergen challenges induced high serum levels of allergen-specific IgE, predominant Th2-type cytokine production, airway inflammation and development of in vivo airway hyperreactivity. Vaccination with diphtheria and tetanus toxoids prior to sensitization suppressed IgE formation and development of eosinophilic airway inflammation. Co-vaccination with a whole cell pertussis vaccine inhibited allergen sensitization, airway inflammation and development of in vivo airway hyperreactivity. Prevention was due to an allergen-specific and general shift from a predominant Th2 towards a predominant Th1 immune response. CONCLUSION: Vaccination with diphtheria and tetanus toxoids alone or in combination with whole cell pertussis vaccine prior to allergen sensitization prevented allergen-induced Th2 immune responses. Vaccine antigens may down-regulate allergic responses to a range of common allergens.

Allergens↗
PubMed2004

Assessing dimensional and categorical aspects of depression: validation of the AMDP Depression Scale.

BACKGROUND: A new observer depression scale which is based on the descriptive operationalized classification principles of ICD-10 is introduced. The AMDP Depression Scale (AMDP-DS), a 22-item clinician-rated inventory, provides the opportunity of dimensional as well as categorical depression severity assessment. METHODS: A sample of 50 patients with depressive symptoms were assessed with the AMDP-DS by two raters in a joint rater session. A number of widely used depression scales were applied separately by an independent rater. The ICD-10 symptom checklist was used for categorical assessment of depressive disorders. RESULTS: The inter-rater reliability for the total score of the AMDP-DS was excellent (Intraclass coefficient: 0.97). There were high correlations with the sum scores of the other scales under study. The correlations between the ICD-10 symptom-checklist and the AMDP-DS ranged from 0.75 to 0.89 for the total sample and 0.44 to 0.51 for patients with acute depressive episode. LIMITATIONS: The results are limited by the method of a joint rater setting and the relatively small subsample of patients with depressive episode. CONCLUSIONS: The AMDP-DS satisfies the requirements of psychometric criteria with a sufficient degree. A new depression scale designed to cover dimensional as well as categorical aspects has successfully been developed.

Adult↗
PubMed2004

Resiquimod, a new immune response modifier from the family of imidazoquinolinamines, inhibits allergen-induced Th2 responses, airway inflammation and airway hyper-reactivity in mice.

BACKGROUND: Allergen-induced sensitization and airway disease are the results of adverse immune reactions against environmental antigens that may be prevented or inhibited by immune modifying strategies. OBJECTIVE: To investigate the effects of the novel immune response modifier resiquimod (R-848), from the family of imidazol-derivates, in a murine model of allergen-mediated Th2-immune responses and concomitant airway inflammation and airway hyper-reactivity. METHODS: BALB/c mice were systemically sensitized with ovalbumin (OVA) on days 1 and 14 and challenged with OVA aerosol on days 28 and 29. R-848 was applied intranasally to sensitized animals once prior to the first allergen airway challenge, on day 27. RESULTS: A single application of R-848 significantly reduced numbers of eosinophils and lymphocytes in bronchoalveolar lavage fluid and inhibited mucus gland hyperplasia, compared with sensitized and challenged controls. Associated with the decrease in airway inflammation, single intranasal treatment with R-848 abolished the development of airway hyper-reactivity after allergen sensitization and airway challenges. Additionally, Th2-cytokine production in lung tissues from sensitized and R-848-treated animals was reduced, whereas IL-12 and IFN-gamma production was increased, compared with non-treated sensitized mice. CONCLUSION: These data indicate that R-848 effectively inhibits allergen-induced airway inflammation and hyper-reactivity by modulation of increased Th2-immune responses.

Allergens↗
PubMed2001

[Prophylactic long-term therapy of affective disorders with lithium, valproic acid and carbamazepine--effectiveness and cost-effectiveness].

Affective disorders have a substantial public health impact due to morbidity, mortality, quality of life impairment and economic implications. There has been renewed debate of the efficacy and effectiveness of Lithium in long-term treatment of affective disorders. In the present paper current literature is discussed with a focus on the routine use of Lithium (effectiveness) and on cost aspects. Recent reviews have confirmed the prophylactic efficacy of Lithium in bipolar affective disorders. However, there is some evidence that effectiveness studies do not hold what efficacy research would promise. Non-compliance is likely to be a major reason for this. Lithium response rates have declined in recent studies. This may be related to diagnostic change (broader concept of affective disorders) and more widespread Lithium use. Non-compliance in patients taking Lithium is a primary factor in relapse with substantial cost effects (due to inpatient care). Current studies compare Lithium with Valproic acid/divalproex, and find cost advantages for the latter possibly due to better compliance. A special suicide-preventive effect has only been proven for Lithium. To ensure the full prophylactic potential of Lithium compliance needs to be improved. Future studies will compare Lithium with Valproic acid/divalproex, Carbamazepine and new treatment strategies more detailed.

Antimanic Agents↗
PubMed2001

Does lithium exert an independent antisuicidal effect?

AIM OF STUDY: Recent investigations have indicated that adequate lithium treatment lowers the suicide mortality associated with affective illness. One important question is whether the mechanism by which lithium prophylaxis may be effective in prolonging survival can be explained exclusively in terms of successful protection against the recurrence of depressive episodes, or whether one should consider an independent anti-suicidal factor. METHODS: We investigated a group of high-risk patients with recurrent affective disorders (n = 167) who had committed one or more suicide attempts before the start of lithium prophylaxis within a collaborative project by the International Group for the Study of Lithium Treated Patients (IGSLI). According to their recurrence-related response to long-term lithium prophylaxis, patients were classified into three groups: excellent (n = 45), moderate (n = 81) and poor responders (n = 41). Only depressive episodes resulting into hospitalisation were considered. A marked reduction in the number of suicide attempts was observed in the excellent lithium responders. However, we also found that over 80% of moderate responders and nearly 50% of poor responders did not exhibit any further suicidal behaviour during lithium treatment. Furthermore, we could demonstrate a significant reduction of suicide attempts per year as compared to a corresponding pre-lithium period in all three groups (0.10 vs. 0.33, 0.06 vs. 0.27, 0.02 vs. 0.26). There were four suicides in this high-risk group, corresponding to a suicide-related standardised mortality ratio (SMR) of 13.7. This contrasts sharply with an expected suicide SMR of approx. 100 in this population. Suicide risk was not related to the recurrence-preventing effect. CONCLUSION: The reduction in suicide attempts, in both responders and non-responders, indicates that lithium possesses a specific anti-suicidal effect besides its mood-stabilising property.

Adult↗
PubMed2001

Metabolism of orally administered androstenedione in young men.

Androstenedione is a steroid hormone and the major precursor to testosterone. It is available without prescription and taken with the expectation that it will be converted to testosterone endogenously and increase strength and athletic performance. The metabolism of orally administered testosterone has not been well studied. We randomly assigned 37 healthy men to receive 0, 100, or 300 mg oral androstenedione in a single daily dose for 7 d. Single 8-h urine collections were performed on the day before the start of the androstenedione administration and on d 1 and 7 to assess excretion rates of free and glucuronide- conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone. Serum testosterone glucuronide concentrations were measured by frequent blood sampling over 8 h on d 1 in 16 subjects (5 each in the 0 and 100 mg group and 6 in the 300 mg group). In the control group, mean (+/-SE) d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 3 +/- 1, 215 +/- 26, 175 +/- 26, and 0.4 +/- 0.1 microg/h, respectively. In the 100 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 47 +/- 11, 3,836 +/- 458, 4,306 +/- 458, and 1.6 +/- 0.2 microg/h, respectively. In the 300 mg group, mean d 1 and 7 excretion rates for testosterone, androsterone, etiocholanolone, and dihydrotestosterone were 115 +/- 39, 8,142 +/- 1,362, 10,070 +/- 1,999, and 7.7 +/- 1.5 microg/h, respectively. Urinary excretion rates of all metabolites were greater in both the 100 and 300 mg groups than in controls (P < 0.0001). Urinary excretion rates of testosterone (P = 0.007), androsterone (P = 0.009), etiocholanolone (P = 0.0005), and dihydrotestosterone (P < 0.0001) were greater in the subjects who received 300 mg androstenedione than in those who received 100 mg. In the treated groups, excretion of free testosterone accounted for less than 0.1% of the total excreted testosterone measured. Serum testosterone glucuronide levels increased significantly during frequent blood sampling in both the 100 and 300 mg groups compared with controls (P = 0.0005 for the 100 mg group; P < 0.0001 for the 300 mg group). The net mean changes in area under the curve for serum testosterone glucuronide were -18 +/- 25%, 579 +/- 572%, and 1267 +/- 1675% in the groups receiving 0, 100, and 300 mg/d androstenedione, respectively. We conclude that the administration of both 100 and 300 mg androstenedione increases the excretion rates of conjugated testosterone, androsterone, etiocholanolone, and dihydrotestosterone and the serum levels of testosterone glucuronide in men. The magnitude of these increases is much greater than the changes observed in serum total testosterone concentrations. These findings demonstrate that orally administered androstenedione is largely metabolized to testosterone glucuronide and other androgen metabolites before release into the general circulation.

Administration, Oral↗
PubMed2000

Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study.

Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.

Adult↗
PubMed2000

Gold and silver complexes with the ferrocenyl phosphine FcCH2PPh2.

Linear gold(I) and silver(I) complexes with the ferrocenyl phosphine FcCH2PPh2 [Fc = (eta5-C5H5)Fe(eta5-C5H4)] of the types [AuR(PPh2CH2Fc)], [M(PPh3)(PPh2CH2Fc)]OTf, and [M(PPh2CH2Fc)2]OTf (M = Au, Ag) have been obtained. Three-coordinate gold(I) and silver(I) derivatives of the types [AuCl(PPh2CH2Fc)2] and [M(PPh2CH2Fc)3]X (M = Au, X = ClO4; M = Ag, X = OTf) have been obtained from the corresponding gold and silver precursors in the appropriate molar ratio, although some of them are involved in equilibria in solution. The crystal structures of [AuR(PPh2CH2Fc)] (R = Cl, C6F5), [AuL(PPh2CH2Fc)]OTf (L = PPh3, FcCH2PPh2), [Au(C6F5)3(PPh2CH2Fc)], and [Ag(PPh2CH2Fc)3]OTf have been determined by X-ray diffraction studies.

Journal Article↗
PubMed2000

Oral androstenedione administration and serum testosterone concentrations in young men.

CONTEXT: Androstenedione, a steroid hormone and the major precursor to testosterone, is available without prescription and is purported to increase strength and athletic performance. The hormonal effects of androstenedione, however, are unknown. OBJECTIVE: To determine if oral administration of androstenedione increases serum testosterone levels in healthy men. DESIGN: Open-label randomized controlled trial conducted between October 1998 and April 1999. SETTING: General clinical research center of a tertiary-care, university-affiliated hospital. PARTICIPANTS: Forty-two healthy men aged 20 to 40 years. INTERVENTION: Subjects were randomized to receive oral androstenedione (either 100 mg/d [n = 15] or 300 mg/d [n = 14]) or no androstenedione (n = 13) for 7 days. MAIN OUTCOME MEASURES: Changes in serum testosterone, androstenedione, estrone, and estradiol levels, measured by frequent blood sampling, compared among the 3 treatment groups. RESULTS: Mean (SE) changes in the area under the curve (AUC) for serum testosterone concentrations were -2% (7%), -4% (4%), and 34% (14%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P<.001) but not for the 100-mg/d group (P = .48). Baseline testosterone levels, drawn 24 hours after androstenedione administration, did not change. Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in the estradiol AUC was significant for both the 300-mg/d (P<.001) and 100-mg/d (P = .002) groups. There was marked variability in individual responses for all measured sex steroids. CONCLUSIONS: Our data suggest that oral androstenedione, when given in dosages of 300 mg/d, increases serum testosterone and estradiol concentrations in some healthy men.

Administration, Oral↗
PubMed2000

Impact of in utero Th2 immunity on T cell deviation and subsequent immediate-type hypersensitivity in the neonate.

It was the aim of this study to analyze the impact of maternal Th2 immune responses on onset and subsequent development of allergen-specific immunity and immediate-type hypersensitivity in early childhood. In a well characterized mouse model of Th2 immunity, BALB / c mice were sensitized to ovalbumin (OVA) before mating followed by allergen aerosol exposure during pregnancy. At the end of pregnancy mice developed allergen-specific Th2 / Th0 immunity and immediate-type hypersensitivity responses to OVA. T cells from these newborns, when restimulated with PMA / ionomycin, demonstrated a lowered capacity to produce IFN-gamma. To assess whether prenatal allergen exposure favors postnatal onset of a Th2-type immune response, these offspring were immunized to a novel antigen by a single injection of beta-lactoglobulin (BLG). In contrast to offspring from non-sensitized mothers, offspring from OVA-sensitized mice showed both higher anti-BLG immunoglobulin titers and higher frequencies of immediate-type skin test responses. Our data suggest that Th2 / Th0 immunity present during pregnancy has a decisive impact on shaping of the Th1 / Th2 T cell profile in the neonate. Furthermore, this effect favors the development of Th2 immune responses, when mice are exposed to a novel antigen during early childhood.

Animals↗
PubMed2000

[Omega-3 fatty acids in psychiatry].

Omega-3 fatty acids (ALA, EPA, DHA) are essential polyunsaturated fatty acids. Due to their pivotal involvement in signal transduction processes in the CNS, a role for these fatty acids in psychiatric disorders has been postulated. This review summarizes the latest findings on the physiological function of these compounds in the CNS and gives a comprehensive overview on the emerging therapeutic role of these psychoactive drugs in psychiatric disorders, with special emphasis being put on affective disorders and schizophrenia.

Brain↗
PubMed2000

Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.

BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.

Adult↗
PubMed2000

Screening, identification and quantitation of benzodiazepines in serum by solid phase extraction on a cyanopropyl phase using high performance liquid chromatography and photodiode array detection.

A screening procedure for benzodiazepines in serum is presented. The compounds are extracted over a cyanopropyl phase followed by identification and determination via high performance liquid chromatography and photodiode array detection. Diazepam (CAS 439-14-5), flunitrazepam (CAS 1622-62-4), nordazepam (CAS 1088-11-5), oxazepam (CAS 604-75-1) and temazepam (CAS 846-50-4) are quantified. Retention data of 42 benzodiazepines and their metabolites as well as hydrolysis products are listed. This assay leads to an expansion of a known systematic toxicological analysis system to identify pharmaceuticals, drugs of abuse and pesticides.

Anti-Anxiety Agents↗