Biomedical subjects

G Wegener

Publications and source records attributed to G Wegener.

At least 19 recordsLinked to original sources

PubMed2006

[Preoperative radiochemotherapy of advanced resectable cancer of the oral cavity with cisplatin vs paclitaxel/carboplatin. Analysis of two multimodality treatment concepts].

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local tumor control and to decrease the incidence of distant metastases. Platinum-based chemotherapy regimens are widely accepted as standard treatment in advanced head and neck cancer. Due to their remarkable activity as well as radiosensitizing effects, taxanes play in increasing role in multimodality treatment concepts of solid tumors. MATERIAL AND METHODS: Since 1989 a total of 85 patients with advanced squamous cell carcinoma of the oral cavity and oropharynx were recruited to participate in two different prospective clinical trials of preoperative chemoradiation. Both treatment concepts (study A: cisplatin 12.5 mg/m(2) plus radiation 36 Gy vs study B: Taxol 40 mg/m(2)/carboplatin AUC 1.5 plus radiation 40 Gy) were compared and further statistical analysis including descriptive analysis as well as univariate and multivariate analysis was performed. RESULTS: At the time of the analysis a total of 47 patients (55.3%) were alive, 38 patients (44.7%) died from tumor-related causes. The overall survival for both patient groups at 5 years was 45.1% (study A) and 84.9% (study B) and after 10 years 32.4% for study group A. A comparative analysis of both groups revealed a highly significant survival benefit at 4 years for study B (p=0.0015). In various calculation models of the multivariate analysis the regimen containing Taxol/carboplatin (study B) was superior to the cisplatin regimen (study A). CONCLUSION: Based on a retrospective analysis of two different concepts of preoperative chemoradiation and supported by recent data from the literature it is justified to conclude that taxane-based combination regimens are more effective compared to cisplatin-based regimens.

Aged↗

PubMed2005

Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels.

The prognostic value of bFGF for surgically treated renal cell cancer (RCC) patients was evaluated by immunohistochemistry (IHC) and the tissue microarray technique (TMA). Additionally, preoperative serum bFGF levels were correlated to tumour stage and the presence of metastases at initial diagnosis. Serum levels of bFGF were measured by ELISA in 39 healthy volunteers, in 37 patients with benign urologic diseases and in 74 RCC patients, 26 of whom revealed lymph node or distant metastases. bFGF expression as detected by IHC was investigated in 777 tissue cores from 259 different RCC patients [median follow-up: 138 (36-240) months]. Eighty eight patients died from tumour progression. For each patient, the TMA slides contained a tissue core from the primary tumour, its invasion front and the normal renal parenchyma. bFGF serum levels were higher in RCC patients vs healthy volunteers (P<0.01) and vs patients with benign urologic diseases (P<0.01). Metastasized patients revealed higher bFGF serum levels than organ-confined specimens (P<0.01). As detected by IHC only increased bFGF expression in the invasion front tissue correlated with the patients' long-term survival (log rank test) (P=0.03). In multivariate analysis regional LN metastases (P<0.01), the histological grading (P<0.01), and an increased bFGF expression in the invasion front (P=0.04) independently predicted the patients' clinical prognosis. Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas. The value of bFGF serum levels as indicators of systemic tumour dissemination remains to be determined.

Adult↗

PubMed2005

The therapeutic value of adrenalectomy in case of solitary metastatic spread originating from primary renal cell cancer.

INTRODUCTION: Solitary adrenal metastases occur in about 1.2-10% of renal cell cancer patients. Since the vast majority of intraadrenal lesions can be detected preoperatively, we and others have recently recommended to renounce a routine adrenalectomy during surgery of renal cell cancer. However, the impact of adrenalectomy on the patients' clinical prognosis in case of a solitary metastatic lesion within the adrenal gland remains an issue of controversial discussion. Whereas some authors suggest adrenalectomy as a potentially curative treatment option in these cases, others compare its clinical value with that of a mere lymphadenectomy. PATIENTS AND METHOD: Between 1981 and 2000, 648 patients (440 males and 208 females) underwent nephrectomy in combination with adrenalectomy in our clinic for the diagnosis of renal cell cancer. The median age at first diagnosis was 59 (range 33-84) and 60 (range 20-85) years for male and female patients, respectively. The median postoperative follow - up was 2.4 years (0.2-18 years). According to the TNM - classification system (2003) tumor stages were classified as follows: T1, 228 pat. (37%); T2, 70 pat. (11%); T3, 287 pat. (46%); T4, 37 pat. (6%). In total, 339 patients revealed regional lymph node or distant metastases at the time of the surgical treatment. Although metastases of the adrenal gland were diagnosed in 48 patients, solitary intraadrenal metastases without further systemic spread were observed in only 13 cases. Several patients' and tumor characteristics (age, tumor stage and size, the presence of regional lymph node metastases, the presence of metastatic lesions at different organ sites as well as the detection of solitary intraadrenal metastases) were correlated with the patients' overall survival by univariate and multivariate statistical analysis (logistic Cox regression analysis). RESULTS: The median long - term survival was 4.8 years for the entire cohort of patients investigated. The median long - term survival was 13.8 years and 11.7 years for patients with no evidence of metastatic spread as well as for patients with a solitary intraadrenal metastatic lesion, respectively. Accordingly, the long - term survival rates at 5 and 10 years after surgery were 66%/50% and 51%/51% for patients with no evidence of metastatic spread or isolated intraadrenal metastases. This difference was not statistically significant. In contrast, for patients revealing lymph node or distant metastases at other organ sites, the median long - term survival was significantly decreased (lymph node metastases: 0.7 years; distant metastases: 1.2 years). DISCUSSION: For patients with a solitary intraadrenal metastatic lesion, adrenalectomy is a potentially curative treatment option. The observation that the long - term survival of the latter patients is comparable to that of patients with organ - confined disease might suggest the establishment of a separate TNM - category for patients revealing a solitary metastasis within the adrenal gland and no hint at further systemic metastatic spread.

Adrenal Gland Neoplasms↗

PubMed2005

Impact of tumor size on the long-term survival of patients with early stage renal cell cancer.

As the biological behaviour of even early stage renal cell cancer (RCC) strongly correlates with tumor size, it has been argued that the inclusion of RCC up to a maximum diameter of 7 cm into a common subgroup classified as T1 according to the 5th edition of the TNM system would not adequately represent the different biological aggressiveness of these malignancies. Taking this into account, the TNM classification, which now categorizes T1 RCC as T1a and T1b according to a cutoff size of 4 cm, was recently modified. However, only a few larger investigations, mainly based on univariate statistical analyses, that support the suitability of this cutoff are at present available from the literature. Therefore, it was the aim of the present investigation to determine the tumor size that best separates patients with low responses from those with high risk for tumor progression by univariate (log rank test) and multivariate (Cox regression model) statistical analyses. Between 1981 and 2000, 652 patients (443 males and 209 females) underwent tumor nephrectomy in our clinic for the diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local growth not extending beyond the renal capsula at the time of surgery. For the different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm) that were selected to subdivide the patients into groups according to the maximum tumor diameter, the correlation between tumor size and overall survival was determined by univariate and multivariate statistical analyses. It became evident that although during univariate analysis the prognostic value of a cutoff size of 4 cm was confirmed, multivariate analysis identified the highest relative risk for cause-specific death (2.93) for patients having tumors larger than 5 cm in maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical prognosis of patients undergoing tumor nephrectomy for early stage RCC. The present study demonstrates the need for multivariate statistical approaches when the latest modification of the TNM classification system is critically evaluated.

Adult↗

PubMed2004

[Recurrent tumors in the oral and maxillofacial region. Results and treatment strategies in 20 years].

UNLABELLED: SUBJECT MATTER: Following clinical diagnosis of a recurrent tumor, curative treatment is seldom available. Depending on the size of the recurrent tumor and the patient's general health condition, extensive surgical resections and reconstructions are avoided in favor of nonsurgical treatment modalities with palliative intent. According to the literature, location of the tumor, tumor size and R-1 and R-2 resection rates are the most frequent reasons for the development of recurrent tumors. PATIENTS AND METHODS: In a retrospective evaluation, a population of 1000 patients who had been treated for primary head and neck cancer during the period from 1979 to 1996 were analyzed descriptively. Survival probabilities of patients with recurrent tumors were calculated according to the Kaplan-Meier product-limit method, and different treatment concepts were compared and analyzed with the log-rank test for significant differences. RESULTS: The largest proportion of primary tumors involved the floor of the mouth (n=369, 36.9%). A total of 198 patients (19.8%) developed recurrent cancer; 79.8% of patients experienced recurrent cancer within 2 years following primary treatment. Within the group of T1/T2 tumors the incidence of recurrent tumors was 28.9%, whereas the incidence in the T3/T4 group was 44.6%. Tumor infiltration of the resection margins was detected in 12.9%. CONCLUSIONS: In line with the literature, tumor infiltration of the resection margins is a relevant prognostic factor; therefore, intraoperative frozen section must be recommended. Treatment with curative intention, in particular extensive surgical resections, is seldom possible and always requires a very intensive discussion with the patient.

Adult↗

PubMed2004

Late relapse after treatment for nonseminomatous testicular germ cell tumors according to a single center-based experience.

The introduction of cisplatin-based systemic chemotherapy into the clinical routine has resulted in a substantial improvement of the recurrence-free and long-term survival of patients with metastatic testicular germ cell tumors. Late relapses after the completion of first-line therapy, comprising systemic chemotherapeutic treatment in combination with a complete resection of residual tumor masses visible in about 25-50% of patients, have been reported to occur in 1-5% of patients later than 2 years following the initial treatment. It has been reported that the risk for the development of late recurrence is correlated to the tumor burden at first diagnosis and/or the presence of teratomatous components within the primary testicular cancer. Second-line chemotherapy in combination with surgery, although not very well standardized, has been recommended as the most effective therapeutic regimen during the treatment of patients suffering from late recurrent germ cell tumors. Herein, we report our single-center experience with 14 patients in different clinical stages who developed late relapse after successful first-line therapy. In the present series, the risk for late relapse was not correlated to the clinical stage at first diagnosis or the presence of teratomatous elements within the primary tumor. It became evident that in selected cases chemotherapy alone can be considered a curative treatment option.

Combined Modality Therapy↗

PubMed2004

Recurrent carcinoma of the head and neck: treatment strategies and survival analysis in a 20-year period.

Following clinical diagnosis of a recurrent tumor, curative treatment is seldom available. Depending on the size of the recurrent tumor and the patient's general health condition extensive surgical resections and reconstructions are avoided in favor of non-surgical palliative intended treatment modalities. According to the literature location of the tumor, tumor size, as well as R-1- and R-2-resection rates are the most frequent reasons for the development of recurrent tumors. In a retrospective evaluation a population of 1000 patients who were treated for a primary head and neck cancer during the period from 1979 to 1996 were analysed descriptively. Survival probabilities of patients with recurrent tumors were calculated according to the product-limit method by Kaplan-Meier, different treatment concepts were compared and analysed with the log-rank test for significant differences. The largest proportion of primary tumors involved the floor of mouth ( n = 369, 36.9%). A total of 198 patients (19.8%) developed a recurrent cancer; 79.8% of patients experienced a recurrent cancer within two years following primary treatment. Within the group of T1/T2 tumors the incidence of recurrent tumors was 28.9%, whereas the incidence in the T3/T4 group was 44.6%. Tumor infiltration of the resection margins was detected in 12.9%. In line with the literature, tumor infiltration of the resection margins is a relevant prognostic factor, therefore intraoperative frozen section must be recommended. Treatment with curative intention, in particular extensive surgical resections, is seldom possible, and requires always a very intensive discussion with the patient.

Adult↗

PubMed2004

Combined chronic treatment with citalopram and lithium does not modify the regional neurochemistry of nitric oxide in rat brain.

A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentation strategy. Also inhibitors of nitric oxide synthase (NOS) have been used as an augmentation strategy, while inhibitors of NOS exhibit antidepressant-like properties in various animal models. Therefore, we hypothesized that modulation of NOS may be involved in the long-term effects of antidepressants and lithium, and studied the influence of acute and chronic administration of citalopram, alone or in combination with lithium, on NOS activity in hippocampus, cerebellum, and frontal cortex, by determination of L-citrulline being formed. We found that administration of acute or chronic citalopram (5 mg/kg and 20 mg/kg/24h, respectively) alone or in combination with subchronic lithium (60 mmol/kg chow pellet) did not influence the activity of NOS ex vivo in all regions compared to control. In contrast, high doses of lithium caused a significant decrease in NOS activity in vitro. We conclude that basal conditions are unsuitable for the study of antidepressant effects on NOS, and that the neurochemistry of nitric oxide remains unaltered following chronic citalopram or subchronic lithium under normal physiological conditions.

Animals↗

PubMed2003

[Is adrenalectomy an indispensable part of nephrectomy? Results of a multivariate statistical analysis].

Since in the absence of clinically overt metastatic disease tumorous lesions within the adrenal gland are found in only 2-10% of cases, the majority of renal cell cancer patients are overtreated by adrenalectomy as an integral part of nephrectomy. The medical records of 847 patients undergoing adrenalectomy in combination with nephrectomy irrespective of the local extent of the primary tumor or the clinical stage at first diagnosis were reviewed to determine the reliability of currently available imaging modalities regarding the prediction of adrenal gland metastases. Several patient and tumor characteristics correlated with the presence of intra-adrenal metastases, and their prognostic value was determined by a multivariate logistic regression model. Metastatic spread into the adrenal gland was observed in 27 of 847 (3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site, preoperative abdominal CT scans were interpreted as false negative. During multivariate statistical analysis, only the presence of distant metastases, vascular invasion within the primary tumor, and multifocal growth of renal cell cancer within the tumor-bearing kidney were identified to independently predict the likelihood for the presence of intra-adrenal metastases. None of the patient or tumor characteristics evaluated reliably predicted the likelihood for the presence of adrenal metastases in patients without evidence of disseminated metastatic spread. As we believe and as the current investigation demonstrates, routine adrenalectomy should not be recommended in cases of preoperatively normal radiological examinations.

Adrenal Gland Neoplasms↗

PubMed2003

[Impact of tumor size on long-term survival of patients with organ-confined renal cell cancer].

PURPOSE: As a result of the observation that the potential biological aggressiveness of even early stage renal cell cancer (RCC) strongly correlates with tumor size, the 5th edition of the TNM system (1997), which classifies all renal tumors up to a maximum diameter of 7 cm as T1, was modified in the current classification to distinguish T1a and T1b tumors based on a cut-off of 4 cm. Only a few larger investigations supporting this cut-off are available in the literature and these are based on univariate statistical analysis. To determine whether this cut-off best reflects the correlation between aggressive potential and tumor size and thus differentiates patients at low or high risk of progression, this investigation was performed using both univariate and multivariate statistical analysis. MATERIALS AND METHODS: Between 1981 and 2000, a total of 652 patients underwent tumor nephrectomy for renal cell carcinoma. Of these, the 243 patients with local RCC not extending beyond the renal capsule were subjected to univariate (log rank test) and multivariate (Cox regression model) statistical analysis. RESULTS: It became evident that, while during univariate analysis the prognostic calue of a cut-off size of 4 cm was confirmed, multivariate analysis identified the highest relative risk of cause-specific death (2.93) in those patients with tumors larger than 5 cm maximum diameter. CONCLUSIONS: The 5 cm cut-off thus appears to best determine the clinical prognosis for patients undergoing tumor nephrectomy for early stage renal call cancer. Taking this into consideration, the present study clearly demonstrates the reed for a multivariate statistical approach when the current modification of the TNM classification system is critically reevaluated.

Adult↗

PubMed2003

Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice.

Several studies have reported the anxiolytic-like effects of various nitric oxide synthase inhibitors in distinct animal models. However, in the context of anxiety, the possible involvement of cyclic GMP, believed to be one of the main targets of NO, remains obscure. Cyclic GMP is degraded by the specific phosphodiesterases in the brain. Therefore, we studied the effect of the selective phosphodiesterase type 5 inhibitor sildenafil in the mouse elevated plus-maze test of anxiety and in the open field test of locomotion. We found that sildenafil (0.05-10 mg/kg i.p.) alone did not affect the behavior of animals in the plus-maze or open field tests, but the anxiogenic beta-carboline DMCM given in a subconvulsive dose (2 mg/kg i.p.) decreased the time spent on open arms in the elevated plus-maze. Treatment with the NO precursor L-arginine (200 mg/kg i.p.) did not modify the behavior of animals in the plus-maze, however, when sildenafil (1 mg/kg i.p.) was administered in combination with L-arginine (200 mg/kg i.p.), both the time spent on the open arms and the percentage of open arm visits were significantly decreased. We conclude that augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice.

Animals↗

PubMed2002

Energy metabolism and metabolic rate of the alder leaf beetle Agelastica alni (L.) (Coleoptera, Chrysomelidae) under aerobic and anaerobic conditions: a microcalorimetric study.

In early fall, adult alder leaf beetles (Agelastica alni L.) retreat, for overwintering, to the top layer of the soil near their forage trees where the ground gets easily waterlogged so that the beetles will be submerged and cut off from atmospheric oxygen. Hence, unlike most other adult insects, alder leaf beetles encounter hypoxia/anoxia in their natural habitat and this may occur at moderate temperature. Exposing beetles to pure nitrogen gas at 20 degrees C had similar behavioral and metabolic effects as submerging them in water, causing rapid immobility and increasing the content of lactate about sevenfold to some 5&mgr;molg(-1) body weight during 10h anoxia. Recovery from 10 h hypoxia/anoxia in pure nitrogen was complete within about 90min.Hypoxia/anoxia triggered a marked decrease in metabolic activity in the beetles (microcalorimetry at 21.7 degrees C) as indicated by a precipitous drop in their heat flow rate, from 1.39+/-0.27 to 0.08+/-0.04mWg(-1) body weight, i.e. by about 94%, when the flow of gas through the calorimeter was switched from air to pure nitrogen. Post-anoxic recovery was accompanied by a peak in heat flow rate that exceeded the basal normoxic rate by about 50%. The homoeostasis of adenine nucleotides in Agelastica is lost when oxygen is wanting. Submergence at 15 degrees C for three days caused a dramatic fall in ATP, to less than 2% of the normoxic value, and a marked increase in AMP, while the total contents of adenine nucleotides decreased by almost two-thirds. Reduced metabolic activity, combined with the capacity to regenerate ATP after readmission of air, is regarded as a key factor for surviving transient lack of oxygen in alder leaf beetles.

Journal Article↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2001

Antagonistic effects of hypertrehalosemic neuropeptide on the activities of 6-phosphofructo-1-kinase and fructose-1,6-bisphosphatase in cockroach fat body.

Hypertrehalosemic neuropeptides from the corpora cardiaca such as the decapeptide Bld HrTH bring about a profound switch in the metabolic activity of cockroach fat body during which production of the blood sugar trehalose is stimulated while the catabolism of carbohydrate (glycolysis) is inhibited. The mechanisms of the metabolic switch are not fully understood. Incubation of isolated fat body from the cockroach Blaptica dubia with 10(-8) M Bld HrTH, for 10-60 min, stimulated glycogen breakdown and increased the content of the substrates of both the glycolytic enzyme 6-phosphofructo-1-kinase (PFK, EC 2.7.1.11) and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase, EC 3.1.3.11) in the tissue. The glycolytic signal fructose 2,6-bisphosphate was markedly decreased in fat body on incubation with Bld HrTH. The content of ATP was slightly reduced, while the contents of ADP and AMP were increased after incubation with the hormone. Fructose 2,6-bisphosphate is a potent activator of PFK and a strong inhibitor of FBPase purified from fat body. The activity of PFK was decreased by about 90% when the hormone-dependent changes in effectors and substrates in fat body were simulated in vitro. FBPase, in contrast, was activated about 25-fold under these conditions, suggesting the hormone to stimulate gluconeogenesis in fat body. The data support the view that fructose 2,6-bisphosphate is a pivotal intracellular messenger in the hormone-induced metabolic switch from carbohydrate degradation to trehalose production in cockroach fat body.

Adenosine Monophosphate↗

PubMed2001

Nitric oxide modulates lithium-induced conditioned taste aversion.

Nitric oxide (NO) has been shown to affect the behaviour in animal models of depression, anxiety and avoidance learning. Lithium has marked effect in avoidance learning, an effect that can be modulated via the 5-HT system. Experiments were carried out using the conditioned taste aversion (CTA) paradigm to investigate whether administration of NO-modifying drugs, serotonergic drugs and lithium, alone or in combination, induced or affected a CTA. The NO-precursor L-arginine (L-Arg), the non-specific inhibitor of NOS and guanylate cyclase, methylene blue (MB) and the specific NOS inhibitor 7-Nitroindazole (7-NI) all produced CTAs in a dose-dependent fashion. Furthermore, we found that L-Arg counteracted the CTAs induced by LiCl or MB but failed to modulate the CTA produced by 7-NI. The administration of the selective 5-HT1A agonist, 8-OH-DPAT, counteracted the CTAs produced by MB and 7-NI. In contrast, depletion of 5-HT by p-Chlorophenylalanine did not affect the aversions produced by MB and 7-NI, but counteracted the CTA produced by L-Arg. Our results suggest that NO plays a role in the acquisition of the CTA induced by LiCl. Furthermore, the results suggest that the 5-HT1A receptor plays an important role in the CTA induced by MB and 7-NI, thus indicating a possible interaction between the 5-HT and NO systems.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2000

The effect of acute citalopram on extracellular 5-HT levels is not augmented by lithium: an in vivo microdialysis study.

A substantial number of patients do not respond sufficiently to antidepressant drugs and are therefore often co-medicated with lithium as an augmentative strategy. Since lithium has been demonstrated to affect 5-HT neurotransmission, we examined the effect of acute and subchronic lithium on 5-HT levels after a challenge with citalopram. We found that subchronic administration of lithium increases extracellular 5-HT baseline level and decreases the extracellular 5-HIAA baseline. However, we found no evidence that the effect of acute citalopram on extracellular 5-HT levels is augmented by acute or subchronic lithium.

Animals↗

PubMed2000

Endogenous nitric oxide decreases hippocampal levels of serotonin and dopamine in vivo.

Nitric oxide (NO) modulates the levels of various neurotransmitters in the CNS. Here we determined whether the specific nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI), the non-selective inhibitor of guanylate cyclase (GC) and NOS, methylene blue (MB), the NO-precursor L-arginine (L-Arg), and the selective soluble GC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) affect extracellular levels of serotonin (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) in the rat ventral hippocampus by using microdialysis in freely moving animals. Local perfusion of 7-NI (1 mM) and MB (1 mM) significantly increased extracellular level of 5-HT, whereas DA was increased by 7-NI only. Systemic administration of 7-NI (50 mg kg(-1)) and MB (30 mg kg(-1)) increased the extracellular levels of 5-HT and DA. Extracellular levels of 5-HIAA was not influenced by local or systemic MB or 7-NI. In contrast, extracellular level of HVA was decreased by systemic MB and retrodialyzed MB, but was not influenced by 7-NI. Retrodialysis of L-Arg (2 mM) decreased the levels of 5-HT, DA, 5-HIAA and HVA in the hippocampus. Systemic administration of L-Arg (250 mg kg(-1)) decreased the level of 5-HT, but failed to influence DA, 5-HIAA and HVA. Local perfusion of ODQ (400 microM) did not affect 5-HT overflow in the hippocampus. We conclude that NOS inhibitors increased extracellular levels of 5-HT and DA in the rat ventral hippocampus after local or systemic administration, whereas the NO precursor L-Arg had the opposite effect. Thus, endogenous NO may exert a negative control over the levels of 5-HT and DA in the hippocampus. However, this effect is probably not mediated by cyclic GMP.

Animals↗

PubMed1999

Electrophoretic determination of estrogen-induced protein in fish exposed to synthetic and naturally occurring chemicals.

In a first step we investigated whether Leuciscus idus, a fish routinely used to assess the quality of surface water in Germany, is suitable to indicate the presence of endocrine-disrupting chemicals. An electrophoretic method was used to determine estrogen-induced protein in fish serum (presumed vitellogenin). This method was tested by exposing juvenile L. idus to 17 alpha-ethinylestradiol, 17 beta-estradiol and estrone. Nominal concentrations of the steroid were compared with concentrations determined analytically by using GC/MS techniques. Under flow-through conditions, 7 days of exposure to 6 ng/l EE2 significantly induced serum vitellogenin in juvenile L. idus. In juvenile rainbow trout (Oncorhynchus mykiss) 4 ng/l EE2 induced significantly elevated levels of serum vitellogenin. In Danio rerio oral application of 40 micrograms 4-nonylphenol/fish per day during a 3-week exposure period caused a major increase of serum vitellogenin. Physiological protein induction could also be measured in Abramis brama, Cyprinus carpio, Oncorhynchus mykiss, Perca fluviatilis, Rutilus rutilus obtained from natural habitats and in Rhodeus sericeus. The minimum amount of blood required for electrophoretic analysis was 1 microliter which should allow monitoring of small sized fish species as well as juvenile fish.

Animals↗