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Biomedical subjects

D Albrecht

Publications and source records attributed to D Albrecht.

At least 19 recordsLinked to original sources

The CNS renin-angiotensin system.

The renin-angiotensin system (RAS) is one of the best-studied enzyme-neuropeptide systems in the brain and can serve as a model for the action of peptides on neuronal function in general. It is now well established that the brain has its own intrinsic RAS with all its components present in the central nervous system. The RAS generates a family of bioactive angiotensin peptides with variable biological and neurobiological activities. These include angiotensin-(1-8) [Ang II], angiotensin-(3-8) [Ang IV], and angiotensin-(1-7) [Ang-(1-7)]. These neuroactive forms of angiotensin act through specific receptors. Only Ang II acts through two different high-specific receptors, termed AT1 and AT2. Neuronal AT1 receptors mediate the stimulatory actions of Ang II on blood pressure, water and salt intake, and the secretion of vasopressin. In contrast, neuronal AT2 receptors have been implicated in the stimulation of apoptosis and as being antagonistic to AT1 receptors. Among the many potential effects mediated by stimulation of AT2 are neuronal regeneration after injury and the inhibition of pathological growth. Ang-(1-7) mediates its antihypertensive effects by stimulating the synthesis and release of vasodilator prostaglandins and nitric oxide and by potentiating the hypotensive effects of bradykinin. New data concerning the roles of Ang IV and Ang-(1-7) in cognition also support the existence of complex site-specific interactions between multiple angiotensins and multiple receptors in the mediation of important central functions of the RAS. Thus, the RAS of the brain is involved not only in the regulation of blood pressure, but also in the modulation of multiple additional functions in the brain, including processes of sensory information, learning, and memory, and the regulation of emotional responses.

Angiotensins↗

[Integrated Health Care in cardiology at Essen].

This paper reports in detail on a project of Integrated Health Care in cardiology at Essen, Germany. Information on the structure of the contract, the participants, the agreed claiming of benefits and provision of services are provided as well as relevant figures and contact data.

Cardiology↗

Angiotensin-(1-7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas.

The renin-angiotensin system not only plays a critical role in blood pressure control but is also involved in learning and memory mechanisms. In addition to angiotensin (Ang) II, Ang-(1-7) may also have important biological activities in the brain. Here, we show for the first time that Ang-(1-7) enhances long-term potentiation (LTP) in the CA1 region of the hippocampus. Our studies with AT1 receptor antagonists and selective Ang-(1-7) receptor antagonists demonstrate the existence of a distinct Ang-(1-7) receptor in the brain, the G-protein-coupled receptor Mas, encoded by the Mas protooncogene. We also show that the genetic deletion of this receptor abolishes the Ang-(1-7)-induced enhancement of LTP. Thus, we firstly demonstrate that Ang-(1-7) influences the induction of LTP in limbic structures implicating its distinct function in learning and memory mechanisms; secondly, we have identified Mas as a functional receptor for Ang-(1-7) in the brain.

Angiotensin I↗

[Mental health promotion and prevention of mental diseases: are there population-based concepts? Looking abroad].

BACKGROUND: The rising public health relevance of mental health requires increased activities in the field of mental health promotion and prevention. In recent times interest in this sphere increases in Germany. OBJECTIVE: Which kinds of population-based mental health promotion programmes and prevention approaches are internationally available? What can be learned from their example? METHOD: Systematic search of the Internet and literature databases. Analysis and comparison of the available mental health promotion and prevention concepts with regard to targets, sub-targets, target groups, protagonists, settings, outcome indicators and evidence management. RESULTS: Concepts for mental health promotion and prevention programmes exist in England, Australia, the European Union and in Quebec, Canada. The concepts show similarities such as choosing similar settings like work place and schools or similar target groups like caretakers or adults in particular challenging life circumstances. CONCLUSIONS: Concepts for population-based mental health promotion and prevention have been created in some countries. For developing such programmes in Germany one should refer to internationally available experience as well as to own gathered experiences as to own expressions gathered pilot projects and the German Health Target Programme.

Australia↗

HHV-8 DNA in blood and the development of HIV-associated Kaposi's sarcoma in the era of HAART--a prospective evaluation.

OBJECTIVE: To explore the significance of HHV-8 viremia in HIV-positive individuals for the risk of developing Kaposi's sarcoma (KS) in the era of highly active antiretroviral therapy. METHODS: 237 HIV-positive patients were included in this prospective evaluation and followed over an average duration of 34 months. HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were determined. In addition AIDS-defining conditions and antiretroviral therapy were documented of all participating subjects. RESULTS: HHV-8 DNA was detectable in PBMCs of 12.6% out of all individuals. 53.3% of these patients initially complained about KS, although 9.2% of patients without HHV-8 DNA in PBMCs were found on KS as well. Furthermore, four patients in total were observed with newly developed KS during follow up visits. None of these patients were noted with detectable HHV-8 DNA at their initial evaluation. CONCLUSIONS: Prevalence of HHV-8 DNA in PBMCs of subjects in this investigation was quite similar to former investigations. However, new diagnosed KS occurred less frequently than demonstrated in previous studies. All of those observed patients with new KS manifestations were negative for HHV-8 DNA in PBMCs at study entry. This observation differs from earlier studies which have postulated the detection of HHV-8 DNA in PBMCs as a predictive value for development of KS. Due to results as presented, a single HHV-8 DNA test in blood has no predictive value in support of predictability of KS development. With respect toto costs and to a less complicated performance antibody assays should be preferred.

Adult↗

Monitoring of endogenous interferon-alpha and human herpesvirus 8 in HIV-infected patients with Kaposi's sarcoma.

The incidence of AIDS-associated Kaposi's sarcoma has declined since the mid-nineties due to the availability of potent antiretroviral therapy including protease inhibitors. However, Kaposi's sarcoma is still the most common neoplasia in HIV-infected patients. In the pathogenesis of the HIV-associated as well as other forms of this disease an infectious agent seems to play a role, namely the human herpesvirus 8. Even before the discovery of the HIV virus, high levels of an unusual acid-labile form of endogenous interferon alpha were found in patients with AIDS-associated KS. The administration of recombinant interferon alpha evolved as standard therapy for Kaposi's sarcoma in HIV-infected patients with a moderate immunodeficiency in addition to antiretroviral therapy. This investigation monitored the levels of HHV 8 and endogenous interferon in 4 patients with and without Kaposi's sarcoma during the course of HIV-disease. The results of our experiments lead us to two hypotheses: First of all, the pre-therapeutic level of endogenous interferon may be a predictor of the response to an interferon-alpha therapy for HIV-associated Kaposi's sarcoma. Secondly, the determination of HHV 8 DNA in blood of HIV-positive patients may allow conclusions about the risk for the development of Kaposi's sarcoma. However these hypotheses should be tested by monitoring the levels of endogenous interferon and HHV 8 DNA in clinical studies of a greater number of HIV-infected patients.

Adult↗

Genetic deletion of angiotensin AT2 receptor leads to increased cell numbers in different brain structures of mice.

Angiotensin II (Ang II) is a potent vasoactive peptide and displays growth factor-like properties. Different high-affinity Ang II receptor subtypes (AT1A, AT1B and AT2) have been cloned. They are expressed in various brain structures. Additionally, it has been assumed that Mas could interact directly or indirectly with the renin-angiotensin system. The AT1 receptor mediates pressor and mitogenic effects of Ang II, whereas physiological function and signaling mechanisms of the AT2 receptor remain poorly understood. Recent reports have shown that Ang II could mediate apoptosis through AT2 receptors. Since the AT1A, AT2 and Mas knockout mice provide new tools for uncovering potential actions of Ang II, the cell number in different brain structures of male adult wild-type mice and mice deficient for AT1A, AT2 or Mas was evaluated to get more insight into the role of Ang II in central nervous system development. In nearly all investigated brain structures (cortex, hippocampus, amygdala, thalamus), the cell number was significantly higher in AT2-deficient mice in comparison to wild-type mice. To the contrary, in AT1A-deficient mice the cell number was significantly less than in controls in the lateral geniculate and the medial amygdaloid nucleus. However, cell numbers were not changed in Mas-knockout mice compared to their wild-types. These results show the contrary effects of both angiotensin receptors on cell growth and represent the first demonstration of their action on neuronal cell development evidenced in the adult mouse brain.

Angiotensin II↗

Factors associated with clinical assessment of overactive bladder and selection of treatment.

BACKGROUND: Overactive bladder (OAB) affects >17 million individuals in the United States, but the symptoms of OAB are frequently underreported by patients and therefore untreated by physicians. OBJECTIVE: The purpose of this observational study was to investigate the demographic and clinical factors associated with the decision to treat OAB pharmacologically and identify factors associated with physicians' assessment of symptom severity. METHODS: We studied 31 physicians treating 217 patients with OAB and collected data on patient demographic characteristics, OAB symptoms, previous management strategies, physicians' assessments of OAB severity, and treatment prescribed. Stepwise logistic regression was used to identify factors associated with selecting pharmacologic treatment and with physician assessment of severity of OAB symptoms. RESULTS: The mean age of the patients was 61.3 years; approximately 82% were female, and approximately 73% were white. Participants with urinary incontinence were significantly (P < 0.001) more likely to be treated with medication than were those with only symptoms of nocturia or urinary frequency. Other significant factors associated with pharmacologic treatment were being white (odds ratio [OR], 9.5; 95% CI, 2.9-30.8); being black (OR, 5.9; 95% CI, 1.2-29.7); physician's clinical assessment of OAB as moderate (OR, 3.5; 95% CI, 1.5-8.2) or severe (OR, 3.8; 95% CI, 1.1-13.7); previous use of medication (OR, 2.9; 95% CI, 1.1-8.1); and number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.0-1.5). Factors associated with physician assessment of OAB severity included distress due to OAB symptoms (OR, 2.1; 95% CI, 1.3-3.2), number of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.1-1.4), and use of previous treatment(s) (OR, 0.4; 95% CI, 0.2-0.8). CONCLUSIONS: Both demographic and clinical symptoms of OAB were associated with the decision to treat OAB with medication, whereas physicians' assessment of OAB severity was associated only with clinical symptoms. Urinary incontinence was the key symptom associated with the decision to treat patients with medication and with the assessment of OAB symptom severity.

Aged↗

Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia.

OBJECTIVE: To assess the crossreactivity of glucosamine sulfate, used for treatment of degenerative joint disease with antibodies induced in heparin-induced thrombocytopenia (HIT). BACKGROUND: HIT is a severe adverse effect of heparin therapy induced by an immunological mechanism. The antibodies in HIT are induced by a complex of heparin and, in most cases, platelet factor 4. Hereby generation of the antigen is not strictly dependent on heparin. Heparin can be substituted by a variety of polysulfated carbohydrates. In vitro and in vivo crossreactivity of HIT antibodies has been demonstrated for a chemically polysulfated chondroitin-like substance (Arteparon, Luitpoldwerke, Munich, Germany), formerly used for chondroprotection. Another drug widely used in the treatment of degenerative joint disease is glucosamine sulfate. Glucosamine is a building block of glycosaminoglycans, of which heparin is the clinically most important. Many patients with degenerative joint disease use glucosamine sulfate. This group is also at the highest risk to develop HIT following joint replacement surgery. METHODS: We examined the interactions of glucosamine sulfate (DONA 200-S, Opfermann, Wiehl, Germany) with platelets and antibodies of patients with HIT in and without the presence of heparin. Sera of 5 HIT patients and platelets of 4 healthy donors were used. The binding of HIT antibodies to PF4/glucosamine sulfate complexes was assessed by an ELISA. RESULTS: HIT antibodies did not activate platelets in the presence of glucosamine sulfate in a serotonin-release assay. Preincubation with glucosamine sulfate did not inhibit platelet activation by HIT antibodies in the presence of heparin (0.2 IU/ml). Antibodies bonded to PF4/heparin but not to PF4/glucosamine sulfate complexes. CONCLUSIONS: In contrast to sulfated glycosaminoglycans, there is no evidence for an immunological crossreactivity of HIT antibodies between heparin and glucosamine sulfate.

Antibody Specificity↗

Inhibitory action of nociceptin/orphanin FQ on functionally different thalamic neurons in urethane-anaesthetized rats.

1. In this study we administered nociceptin/orphanin FQ (NC) ionotophoretically onto neurons located in functionally distinct thalamic structures of urethane-anesthetized rats. Extracellular single unit recordings were made in the medial and lateral ventroposterior nucleus, posterior thalamic nucleus, zona incerta, lateral posterior nucleus, laterodorsal nucleus, ventrolateral nucleus and reticular nucleus. 2. NC decreased the firing rate in 60% of thalamic neurons. This decrease in firing rate was accompanied by a significant reduction in the number of high threshold bursts. 3. In about 20% of the neurons NC increased the firing rate. In most cells NC-induced increases in discharge rate could be blocked by the GABA(A) receptor antagonists bicuculline and SR 95531. 4. The NC receptor ligands [Phe(1)Psi(CH(2)-NH)Gly(2)] nociceptin(1-13)NH(2), Ac-RYYRIK-NH(2) and [Nphe(1)]NC(1-13)NH(2) were also evaluated. All these peptides inhibited NC-induced changes in firing rate. In addition, in some neurons where NC inhibited firing, [Nphe(1)]NC(1-13)NH(2) and Ac-RYYRIK-NH(2) elicited per se an increase in firing rate, suggesting the existence of tonic innervation of thalamic neurons by NC-containing fibres. 5. In NC-inhibited neurons nocistatin induced a significant increase in firing rate. 6. The present study demonstrated that NC regulates various thalamic nuclei related not only to somatosensory, but also to the visual and motor functions.

Action Potentials↗

Biomechanical analysis of the brachioradialis as a donor in tendon transfer.

Anatomic and biomechanical properties of the passive brachioradialis muscle were investigated to understand the limited excursion of this muscle seen during tendon transfer surgery. First, architectural measurements were performed on three fiber bundles obtained from four regions of the brachioradialis (10 specimens) chosen to represent the range of muscle fiber lengths across the brachioradialis. Next, in separate specimens (eight specimens), passive excursion was measured by securing the distal tendon stump to a servomotor. A constant load of 4.9 N was applied to the tendon, while the distal tendon was released from the surrounding tissue in 3-cm increments. Within the four regions studied, muscle fiber length varied significantly from 104.2 +/- 6.2 mm to 179.8 +/- 6.1 mm. As the brachioradialis was released, an average of 3 mm of mobility was obtained for each interval whereas for the succeeding three intervals, an average of 5.3 mm of mobility was obtained. This resulted in 22.2 +/- 2.3 mm of mobility when each specimen was fully released. These data show that there is no intrinsic muscle fiber length limitation to excursion, but that excursion is limited by other intermuscular connections to adjacent connective tissue and other muscles.

Biomechanical Phenomena↗

Resistance analyses in HIV infected patients with a history of multiple antiretroviral treatment regimens.

OBJECTIVE: To assess HIV-1 isolate based resistance profiles from extensively pretreated patients and effects of a resistance guided switch of antiretroviral therapy. METHODS: In a prospective study phenotypic and genotypic resistance analyses were performed on HIV infected individuals with failure of the current therapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyte counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks. RESULTS: All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations and phenotypic resistance to AZT and 3TC were found in over 80% of individuals; resistance to DDI and D4T was detected in less than 10% of cases. A resistance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or more drugs compared with patients with resistance to less than two drugs of ongoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patients with resistance to at least two drugs in the previous regimen. CONCLUSIONS: Among different RTI, the profile of clinically relevant resistance indicates pronounced differences when looking at separate drugs. Regarding virological response, in the context of available drugs, resistance tested with currently used methods is of limited value in extensively pretreated patients and seems to have its value primarily in first or second switch of therapy.

Adult↗

Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT Study.

OBJECTIVE: To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS: The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS: A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS: Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Aged↗

Studies of tin ethyl etiopurpurin photodynamic therapy of the canine prostate.

PURPOSE: Previous studies have demonstrated the technical feasibility of destroying prostate tissue using photodynamic therapy for benign and malignant disease. A series of canine studies was performed to evaluate the systemic uptake and distribution of the photosensitizer tin ethyl etiopurpurin (SnET2) in the prostate and surrounding tissues, and determine the optimal combination of drug dose, light dose and time interval between drug and light administration using transurethral and transperineal interstitial light delivery. MATERIALS AND METHODS: Adult male mongrel source dogs received intravenous bolus injections of 0.5 or 1.0 mg./kg. SnET2 in 4 studies. In the first study the concentration of SnET2 in the prostate and surrounding tissue was measured at various time points after dosing. In the second study a tissue dose response relationship of SnET2-PDT was studied after transperineal interstitial light application. The third and fourth studies evaluated the tissue effects of combined transurethral and transperineal interstitial light application on SnET2 sensitized prostates. RESULTS: Substantial amounts of SnET2 were measured in the prostate between 24 and 168 hours after infusion. Drug and light dose dependent prostatic tissue necrosis and volume reduction were documented in the dose response relationship study. The combination of transurethral and transperineal light resulted in the extensive destruction of glandular epithelium with minimal damage to surrounding structures. Average prostate volume decreased 52%. Transperineal interstitial light delivery with multiple diffusers resulted in substantial glandular destruction of the prostate. An average volume reduction of more than 60% was achieved. CONCLUSIONS: SnET2-PDT is a viable minimally invasive treatment modality for prostate tissue destruction.

Animals↗

5-HT(1A) receptor-mediated inhibition and 5-HT(2) as well as 5-HT(3) receptor-mediated excitation in different subdivisions of the rat amygdala.

The techniques of extracellular single cell recording and microiontophoresis were used to study the effects of serotonin (5-HT) and of 5-HT(1A), 5-HT(2A/2C) and 5-HT(3) receptor agonists on the spontaneous activity of amygdaloid neurons in rats anesthetized with urethane. The background discharge rate was modified by 5-HT as well as by 5-HT agonists in about two-thirds of neurons tested in different nuclei of the amygdaloid complex. Whereas the 5-HT(2) and 5-HT(3) agonists significantly increased the neuronal discharge rate in nearly all subdivisions of the amygdala, the 5-HT(1A) agonist significantly inhibited the firing rate. Co-administration of bicuculline and 5-HT receptor agonists prevented the 8-OH-DPAT-induced increases in the firing rate in most cases tested, as well as the inhibitory effects of DOI or 2-methyl-5HT. Therefore, GABAergic interneurons seem to be involved in the mediation of serotonergic effects. The action of 5-HT agonists on the neuronal discharge rate was blocked by different receptor-specific antagonists. The results support the hypothesis that 5-HT exerts control throughout the amygdala by acting at least on 5-HT(1A), 5-HT(2A/2C) and 5-HT(3) receptors seemingly located both on projection and interneurons.

Action Potentials↗

Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia. Report of four cases and review of literature.

Differential diagnosis between post-transfusion purpura (PTP) and heparin-induced thrombocytopenia (HIT) can be difficult in the initial stages of thrombocytopenia, as the early clinical presentations are often similar. Four patients are described who were suspected clinically of suffering from HIT. All four patients had recent blood transfusions and platelet alloantibodies, thus the diagnosis of PTP was made. One lethal gastrointestinal and one retroperitoneal hemorrhage developed in two of the four patients. Unusually, one patient was male and two different platelet alloantibodies were present in his serum; in another patient platelet alloantibodies and HIT-antibodies were detectable. To arrive at the right diagnosis as quickly as possible is vitally important since treatment, which has to be initiated promptly, is very different for the two syndromes. Thus, we suggest that in patients where HIT is suspected, additional information should be sought. If features consistent with PTP (such as a recent blood transfusion or a marked drop in platelet count to below 15 Gpt/L) are present, we recommend parallel testing for platelet alloantibodies to rule out PTP.

Acute Disease↗

Various effects of angiotensin II on amygdaloid neuronal activity in normotensive control and hypertensive transgenic [TGR(mREN-2)27] rats.

The effects of iontophoretically ejected angiotensin II (Ang II) on the firing rate of neurons in the basolateral complex and the central and cortical amygdala were investigated in two strains of urethane anesthetized rats. In normotensive Sprague-Dawley rats, Ang II induced a significant increase in the discharge rate of responsive amygdaloid neurons. In contrast, in the hypertensive transgenic [TGR(mREN-2)27] rats with higher brain Ang II level, Ang II more often caused inhibitory effects on the amygdaloid firing rate in comparison with controls. The distribution of nonresponsive, excited, and inhibited neurons differed significantly in the two rat strains. Moreover, the responsiveness of amygdaloid neurons was significantly higher in transgenic rats in comparison with controls. Both the increase and the decrease in the firing rate caused by Ang II could be blocked either by angiotensin AT(1) or by AT(2) receptor-specific antagonists. In many cases, the Ang II-induced decrease in the firing rate was antagonized by bicuculline, a gamma-aminobutyric acid (GABA(A)) antagonist. The higher responsiveness of amygdaloid neurons in transgenic rats as well as the predominance of inhibitory effects, presumedly mediated by GABAergic interneurons, could change the output of the amygdala and its influence on thirst, kidney, and cardiovascular function or on processes of learning and anxiety.

Amygdala↗

Interaction between Mas and the angiotensin AT1 receptor in the amygdala.

The Mas-protooncogene is a maternally imprinted gene encoding an orphan G protein-coupled receptor expressed mainly in limbic structures of the rodent CNS. Because Mas and the product of the Mas-related gene enhance the effects of angiotensins on cells expressing angiotensin receptors of the AT1 subtype, we first compared the distribution of cells expressing AT1 receptors in different limbic and thalamic brain structures in Mas-knockout mice and in wildtype mice by an immunohistochemical approach. No significant differences could be found between the two strains. The Mas-protooncogene seems to be implicated in the signal transduction of angiotensin receptors and is expressed in the amygdala. Therefore we then analyzed whether field potentials are altered by angiotensin II in brain slices of the basolateral amygdala. An opposite action of angiotensin II was obtained in mice lacking the Mas-protooncogene in comparison to wildtype mice. The use of different angiotensin receptor antagonists provides the first in vitro evidence for a functional interaction between the Mas-protooncogene and the AT1 receptor.

Action Potentials↗