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G Franke

Publications and source records attributed to G Franke.

At least 19 recordsLinked to original sources
PubMed2006

Tyramine in the assessment of regional adrenergic function.

Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue with microdialysis probes in normal subjects. We measured glycerol concentrations to follow changes in lipolysis and monitored tissue perfusion with ethanol dilution. During perfusion with tyramine, dialysate glycerol concentration increased dose-dependently from 83+/-8 microM at baseline to 181+/-18 microM at 3.5 mM tyramine (p<0.001) followed by a fall down to 121+/-9 microM at 35 mM tyramine (p<0.001). Propranolol almost completely blocked this response. A similar lipolytic response was not observed in isolated human adipocytes. Dopamine <35 microM did not replicate the tyramine-induced lipolysis; however, dopamine >35 microM potently inhibited lipolysis. We conclude that tyramine-induced lipolysis is explained by a pre-synaptic mechanism. Tyramine applied through a microdialysis probe in concentrations up to 3.5 mM can be used to assess pre- and post-synaptic mechanisms regulating lipid mobilization.

Adipocytes↗
PubMed2006

The effect of oral glucose loads on tissue metabolism during angiotensin II receptor and beta-receptor blockade in obese hypertensive subjects.

AT1 receptor blockers and ACE inhibitors decrease the risk for new onset diabetes mellitus. The phenomenon could be related to a direct angiotensin II effect on tissue metabolism. To address the issue, we recruited eighteen obese hypertensive patients. Patients were randomized to double-blind treatment with either valsartan (n = 8) or atenolol (n = 10) for thirteen weeks. They underwent an oral glucose tolerance test before and during active treatment, while metabolism was monitored through subcutaneous and intramuscular microdialysis and indirect calorimetry. After glucose ingestion, venous glucose and insulin concentrations increased rapidly while systemic free fatty acid concentrations were suppressed. Dialysate glucose and lactate concentrations increased briskly in adipose tissue and in skeletal muscle. Dialysate glycerol decreased profoundly in both tissues. Respiratory quotient increased markedly after glucose ingestion. These responses were identical at baseline and during active treatment either drug. We conclude that AT1 receptor blockade in obese hypertensive patients has no effect on interstitial glucose supply, lipolysis, and substrate oxidation. One possible explanation is that angiotensin II levels in obese hypertensives are not sufficient to elicit the metabolic changes that have been observed after direct angiotensin II application. The exact mechanism by which inhibition of the renin-angiotensin-aldosterone system decreases the diabetes risk remains unresolved and requires further study.

Adipose Tissue↗
PubMed2005

Osmosensitive mechanisms contribute to the water drinking-induced pressor response in humans.

BACKGROUND: Water drinking elicits a sympathetically mediated pressor response in multiple-system atrophy patients through an unknown mechanism. We reasoned that gastrointestinal distention, hyposomotic stimulation, or both contribute to the water-induced pressor response. METHODS: We compared the response to normal saline and water on blood pressure in 10 patients with probable multiple-system atrophy. Patients featured moderate to severe autonomic dysfunction. EKG and finger arterial blood pressure were recorded continuously, and 500 mL normal saline and distilled water were each given in a single-blinded fashion. Fluids were applied through a previously inserted nasogastric tube within a 5-minute period. RESULTS: Blood pressure began to increase within 10 minutes after water administration and reached a maximum after 20 minutes. Blood pressure did not change after saline administration. The blood pressure change after 20 minutes was 8 +/- 9/2 +/- 5 mmHg with water and -1 +/- 11/-1 +/- 7 mmHg with normal saline administration (p = 0.02 between interventions). Heart rate did not change with either intervention. CONCLUSION: Ingestion of water elicits a greater pressor response than the ingestion of normal saline. Thus, gastric distention is probably not the crucial mechanisms for the water-induced pressor response. Instead, the response may be mediated through osmosensitive afferent structures in the gastrointestinal tract, portal vein, and liver.

Autonomic Nervous System Diseases↗
PubMed2004

Hypothalamic neuropeptide release after experimental subarachnoid hemorrhage: in vivo microdialysis study.

OBJECTIVES: As evidence exists about independent regulation of peripheral and central release of the vasoactive and natriuretic neuropeptides arginine-vasopressin (AVP) and oxytocin (OXT), we investigated their release patterns following subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: After injection of 0.1 ml arterial blood or saline into the great cistern of 33 Wistar rats, AVP and OXT levels were measured in blood and by microdialysis in the hypothalamic supraoptic (SON) and paraventricular nucleus (PVN). For statistical analysis, the analysis of variance (ANOVA) was used with Tukey HSD post hoc ANOVA tests to determine specific group differences. RESULTS: Plasma AVP and OXT peaked 2 h after SAH (P < 0.05), and normalized at 4 h. In the SON, both AVP and OXT peaked 4 h after SAH (P < 0.05). In the PVN, AVP increased in both groups (P < 0.05), while no OXT release occurred. By the sham group, any effect of experimental procedure was excluded. CONCLUSIONS: The SAH-specific central neuropeptide release, which exceeded peripheral release and continued longer, may contribute to pathophysiological events following SAH.

Animals↗
PubMed2003

Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries.

BACKGROUND: The aetiology of atypical haemolytic uraemic syndrome (aHUS) is, in contrast to classical, Shiga-like toxin induced HUS in children, largely unknown. Deficiency of human complement factor H and familial occurrence led to identification of the factor H gene (FH1) as the susceptibility gene, but the frequency and relevance of FH1 mutations are unknown. METHODS: We established a German registry for aHUS and analysed in all patients and 100 controls the complete FH1 gene by single strand confirmational polymorphism and DNA sequencing. In addition, complement C3 and factor H serum levels were assayed. Demographic data at onset of aHUS and follow up were compared for the mutation positive and negative groups. RESULTS: Of 111 patients with aHUS (68 female, 43 male, mean age 33 years) 14% had FH1 germline mutations, including two of eight patients with familial aHUS. For each of these eight patients, both parents were tested, and we were able to trace the mutation for five cases. In the other three cases (one with the mutation 3749 C/T, one with 3200 T/C, and one with 3566+1 G/A), we could not detect the mutation in either parent, although paternity was proven by genetic fingerprinting, suggesting that these subjects have new mutations. C3 was decreased in five mutation carriers but also in two non-carriers, and factor H was decreased in none of the carriers, but elevated in six carriers and 15 non-carriers. Clinical parameters including associated medications and diseases, and outcome of aHUS and of post-aHUS kidney transplantation were similar in the mutation positive and negative groups. CONCLUSION: FH1 germline mutations occur with considerable frequency in patients with aHUS. Hypocomplementaemia is not regularly associated with a germline mutation, and factor H serum levels can even be elevated. Screening for FH1 mutations contributes to the classification of aHUS.

Adult↗
PubMed2001

Limited effect of systemic beta-blockade on sympathetic outflow.

Central beta-adrenoreceptors may augment sympathetic outflow. We tested the hypothesis that beta-blockade attenuates central sympathetic outflow by inhibiting central adrenoreceptors. We studied 18 healthy controls (4 female, 14 male; age, 26+/-6 years, body mass index, 23+/-3 kg/m(2)). ECG, brachial, and finger arterial blood pressure, muscle sympathetic nerve activity, and respiration were measured continuously before and during complete beta-blockade. Subjects received a total intravenous dose of 0.21 mg/kg of propranolol in 15 minutes. Spontaneous baroreflex slopes were calculated using the sequence technique (BRSup, BRSdown). The sympathetic baroreflex slope was determined at baseline using phenylephrine and sodium nitroprusside infusions. The subjects underwent cold pressor testing before and during beta-blockade. The R-R interval increased from 861+/-119 ms at baseline to 952+/-141 ms during beta-blockade (P<0.01). Blood pressure was 117+/-9/65+/-8 mm Hg at baseline and 117+/-10/67+/-8 mm Hg during beta-Blockade (P=NS). beta-Blockade did not affect baroreflex sensitivity (BRSup: 21+/-10 versus 28+/-11 ms/mmHg, P<0.1; BRSdown: 17+/-8 versus 20+/-8 ms/mmHg, P=NS). Muscle sympathetic nerve activity increased significantly during beta-blockade (number of bursts/100 beats: 32+/-9 versus 40+/-14, P<0.05), compared with baseline. However, the operating points of the parasympathetic and sympathetic baroreflex during beta-blockade were on the baroreflex curves obtained at baseline. beta-Blockade blunted the heart rate response to cold pressor testing; blood pressure and muscle sympathetic nerve activity responses were similar. Our study demonstrates that propranolol does not cause an acute decrease in sympathetic activity in normotensive young subjects. This, observation is not consistent with an important tonic stimulatory effect of beta-adrenoreceptors in the brain.

Adrenergic beta-Antagonists↗
PubMed2001

Overexpression of sialyltransferase CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-Sialyltransferase is related to poor patient survival in human colorectal carcinomas.

Thomsen-Friedenreich (TF)-related blood group antigens, such as TF, Tn, and their sialylated variants, belong to a family of tumor-associated carbohydrates. The aim of the present study was to examine tumor-associated alterations of glycosyltransferases involved in the biosynthesis of the TF glycotope in colorectal carcinomas. To this end, glycosyltransferase expression was examined in 40 cases of colorectal carcinoma specimens classified according to the WHO/Union International Contre Cancer guidelines and in "normal" mucosa of the same patients. Occurrence of TF glycotope was examined by immunohistochemistry with the monoclonal antibody A78-G/A7. Expression of sialyltransferases CMP-sialic acid:Galbeta1,3GalNAc-R alpha3-sialyltransferase I and II (ST3Gal-I and ST3Gal-II) and CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-sialyltransferase (ST6GalNAc-II) and of core 2 beta1,6-N-acetylglucosaminyltransferase was determined by reverse transcription-PCR in the same cryostat sections used for immunohistochemistry. Additionally, alpha2,3-sialyltransferase enzyme activity was studied in each of these tissues. The TF glycotope was detected in 7% of the normal mucosa, but in 57% of the carcinoma samples. Expression of alpha2,3-sialyltransferases ST3Gal-I, ST3Gal-II, and enzyme activity of alpha2,3-sialyltransferase was significantly increased (P < 0.001) in carcinoma specimens compared with normal mucosa. ST3Gal-I mRNA expression was significantly increased (P = 0.05) in cases showing invasion of lymph vessels. Expression of ST6GalNAc-II was significantly increased (P = 0.04) in cases with metastases to lymph nodes along the vascular trunk. Moreover, ST6GalNAc-II expression provides an prognostic factor for patient survival (log rank, P = 0.02). In an attempt to study the functional relevance of the glycosyltransferases for TF biosynthesis, SW480 colorectal cells were transfected with each of the enzymes, and cell surface expression of the TF glycotope was examined by flow cytometry. The presence of TF was not altered by transfection of the cells with either sialyltransferase ST3Gal-I or ST3Gal-II. However, successful transfection with core 2 beta1,6-N-acetylglucosaminyltransferase led to reduced expression of TF. In contrast, increased cell surface expression of TF was found after ST6GalNAc-II transfection. Thus, expression of TF on the cell surface of SW480 colorectal carcinoma cells depends on the ratio of core 2 beta1,6-N-acetylglucosaminyltransferase and ST6GalNAc-II. Earlier immunohistological studies demonstrated that TF is a prognostic factor for patient survival. Our results suggest that sialyltransferase ST6GalNAc-II is of crucial relevance for the prognostic significance of TF.

Adult↗
PubMed2001

Genetic influences on baroreflex function in normal twins.

Blood pressure and heart rate are strongly influenced by genetic factors; however, despite the pivotal role of genetics in short-term cardiovascular regulation, little is known about the genetic contribution to baroreflex function. We assessed genetic influence on baroreflex sensitivity (BRS) in 149 twin pairs (88 monozygotic of age 33+/-13 years and BMI 23+/-4 kg/m(2) and 61 dizygotic of age 33+/-11 years and BMI 24+/-4 kg/m(2)). ECG and finger arterial blood pressures were measured continuously under resting conditions. BRS values were calculated by use of cross-spectral analysis (baroreflex slope calculated as mean value of transfer function between systolic blood pressure and the R-R interval in the low-frequency band [BRSLF] and baroreflex slope calculated as the mean value of transfer function between systolic blood pressure and R-R interval in the respiratory frequency band [BRSHF]) and the sequence technique (BRS+, BRS-). Heritability (h(2)) was estimated with a path-modeling approach. BRS values did not differ significantly between groups (monozygotic, BRSLF, 17+/-13; BRSHF, 21+/-18; BRS+, 19+/-16; and BRS-, 21+/-15, and dizygotic, BRSLF, 16+/-9; BRSHF, 20+/-14; BRS+, 18+/-10; and BRS-, 20+/-11 ms/mm Hg), and were significantly correlated (P:<0.001). When variances and covariances for monozygotic and dizygotic twins were compared, significant correlations were found for BRS in monozygotic (range, r=0.38 to 0.48) but not in dizygotic twin pairs (r=-0.03 to 0.09). Thus, BRS is heritable; the variability can be explained by genetic influences (P:<0.01; h(2) range, 0.36 to 0.44). The genetic influence on BRS remained strong after correction for BMI and blood pressure. Therefore, BRS is strongly genetically determined, probably by different genes than are resting blood pressure and BMI.

Adult↗
PubMed2001

Interaction between beta-adrenergic receptor stimulation and nitric oxide release on tissue perfusion and metabolism.

Nitric oxide (NO) may be an important modulator of sympathetic tone. We used im and sc microdialysis in humans to characterize the interaction of NO synthase inhibition and adrenoreceptor stimulation on tissue perfusion, metabolism, and norepinephrine release. Microdialysis probes were perfused with L- or D-nitro-L-arginine-methyl-ester (100 micromol/L) followed by incremental doses of isoproterenol, epinephrine, or nitroprusside. Blood flow was estimated based on the ethanol dilution technique. In muscle, the increase in blood flow with isoproterenol was abolished by L-NAME. The ethanol ratio was 0.03 +/- 0.011 with D-NAME and 0.075 +/- 0.014 with L-NAME during isoproterenol treatment (1 micromol/L). The effect was less pronounced in adipose tissue. The vasodilatory effect of nitroprusside was similar with D- and L-NAME. L-NAME augmented isoproterenol- and epinephrine-induced glycerol release. Dialysate glycerol during 1 micromol/L isoproterenol was 47 +/- 6.7 micromol/L with D-NAME and 72 +/- 15 micromol/L with L-NAME. In skeletal muscle, dialysate norepinephrine during 1 micromol/L isoproterenol treatment was 0.73 +/- 0.17 and 1.3 +/- 0.15 nmol/L with D- and L-NAME, respectively. We conclude that NO synthase inhibition attenuates beta(2)-adrenoreceptor-mediated vasodilation and enhances beta-adrenoreceptor-mediated lipolysis. These effects are in part mediated through an increase in interstitial norepinephrine concentrations. The data are consistent with the idea that in humans, NO is important in modulating and ameliorating sympathetic effects in peripheral tissues.

Adrenergic beta-Agonists↗
PubMed2000

Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein.

OBJECTIVE: Recent data indicated that disposition of oral digoxin is modulated by intestinal P-glycoprotein. The cardioselective beta-blocker talinolol has been described to be secreted by way of P-glycoprotein into the lumen of the gastrointestinal tract after oral and intravenous administration. We therefore hypothesized that coadministration of digoxin and talinolol may lead to a drug-drug interaction based on a competition for intestinal P-glycoprotein. METHODS: Pharmacokinetics of digoxin (0.5 mg orally), talinolol (30 mg intravenously and 100 mg orally), and digoxin plus talinolol orally, as well as digoxin plus talinolol intravenously, were assessed in five male and five female healthy volunteers (age range, 23 to 30 years; body weight, 60 to 95 kg) in a changeover study with at least a 7-day washout period. Digoxin and talinolol were analyzed by fluorescence polarization immunoassay and HPLC, respectively. RESULTS: Oral coadministration of 100 mg talinolol increased the area under the concentration-time curve (AUC) from 0 to 6 hours and the AUC from 0 to 72 hours of digoxin significantly by 18% and 23%, respectively (5.85+/-1.49 versus 7.22+/-1.29 ng x h/mL and 23.0+/-3.3 versus 27.1+/-3.7 ng x h/mL, for both P<.05) and the maximum serum levels by 45%. Renal clearance and half-life of digoxin remained unchanged. Coinfusion of 30 mg talinolol with oral digoxin had no significant effects on digoxin pharmacokinetics. Digoxin did not affect the disposition of talinolol after both oral and intravenous administration. CONCLUSION: We observed a significantly increased bioavailability of digoxin with oral coadministration of talinolol, which is most likely caused by competition for intestinal P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction.

BACKGROUND: P-Glycoprotein is an efflux pump in many epithelial cells with excretory function. It has been demonstrated that rifampin (INN, rifampicin) induces P-glycoprotein, particularly in the gut wall. We therefore hypothesized that rifampin affects pharmacokinetics of the P-glycoprotein substrate talinolol, a beta1-blocker without appreciable metabolic disposition but intense intestinal secretion in human beings. METHODS: Pharmacokinetics of talinolol (a single dose of 30 mg administered intravenously or 100 mg administered orally for 7 days) and duodenal expression of the MDR1 gene product P-glycoprotein as assessed by reverse transcriptase-polymerase chain reaction of the MDR1-messenger ribonucleic acid, by immunohistochemistry and Western blot analysis were analyzed before and after coadministration of rifampin (600 mg per day for 9 days) in 8 male healthy volunteers (age 22 to 26 years). RESULTS: During rifampin treatment, the areas under the curve of intravenous and oral talinolol were significantly lower (21% and 35%; P < .05). Treatment with rifampin resulted in a significantly increased expression of duodenal P-glycoprotein content 4.2-fold (2.9, 6.51) (Western blot) and messenger RNA was increased in six of the eight volunteers. P-Glycoprotein expression in biopsy specimens of gut mucosa correlated significantly with the systemic clearance of intravenous talinolol (rs = 0.74; P < .001). CONCLUSIONS: Rifampin induces P-glycoprotein-mediated excretion of talinolol predominantly in the gut wall. Moreover, clearance of talinolol from the blood into the lumen of the gastrointestinal tract may be predicted by the individual intestinal P-glycoprotein expression. Thus we describe a new type of steady-state drug interaction affecting compounds that are subject to transport rather than metabolism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

[Clinical use of mydriasis with 10% phenylephrine and its antagonism by 0.5% dapiprazole].

BACKGROUND: Dapiprazole hydrochloride is an alpha-1-adrenergic inhibitor that anticipates the mydriatic effect of phenylephrine in dilator muscle receptors in a competitive way. The aim of this study was to determine for which indications for mydriasis pupil dilation by phenylephrine alone is sufficient and if the reversal by dapiprazole is convenient and the practical. MATERIAL AND METHOD: In 286 eyes of 147 outpatients, the pupil was dilated for fluorescein angiography-FLA (100 eyes of 50 patients), examination of the fundus-Fd (99 eyes of 52 patients), central argon laser coagulation-cALC) (64 eyes of 32 patients), peripheral argon laser coagulation-pALC (16 eyes of 9 patients) and Nd:YAG capsulotomy (7 eyes of 4 patients) with phenylephrine 10% eyes drops, followed by reversal by dapiprazole 0.5%. The width and mobility of the pupil were tested at intervals of 10 min. When mydriasis by phenylephrine was insufficient, tropicamide was applied additionally. RESULTS: In 98% of FLA with scanning laser ophthalmoscope, 75% of cALC, 76% of Fd, 62% FLA with fundus camera and 38% of pALC, mydriasis could be reached that was sufficient for the indication. Diabetics showed significantly more sluggish pupil mobility (t1/2: P < 0.05 mydriasis, P < 0.005 reversal). The mean duration after using dapiprazole until reaching the starting value (+/- 1 mm) of the pupil was 44.3 +/- 26.3 min. In 86% of the examined eyes, the pupil reached its starting value within 1 h. The subjective degree of satisfaction with the application of dapiprazole was "satisfied" to "very satisfied" (5.4 +/- 1.4 points on a scale from 1 to 7 points). DISCUSSION AND CONCLUSION: In fundus examination, fluorescein angiography by a laser scanner, diagnostic retinal examination and central laser coagulation, the combination phenylephrine/dapiprazole was most suitable. In our opinion, the combination is less suitable for peripheral argon laser coagulation and fluorescein angiography using a fundus camera.

Adolescent↗
PubMed1999

[Quality of life following transplantation. The impact ofa new immunosuppressive substance].

The improvement of quality of life is one of the major goals in the treatment of patients after renal transplantation. While immunosuppressive therapy is present in almost all of these patients, little is known about the effects of newer immunosuppressive agents. We therefore investigated the impact of tacrolimus on life quality. From November 1997 to January 1998, a questionnaire was handed out which focussed on physical and mental problems as well as sexual capacity and the attitudes towards graft, donor and transplant related side effects. 50 kidney graft recipients treated with tacrolimus were matched to 50 patients with a cyclosporine-based immunosuppression (= controls). Values are given as mean +/- standard deviation. Tacrolimus treated patients had a mean creatinine of 1.8 +/- 0.8 mg/dl, as compared to 1.6 +/- 0.7 mg/dl in controls. The overall status of health was assessed to be good in 82% of the tacrolimus group (controls: 80%). 38% were working full-time (controls: 20%). Only 14% of patients described their physical condition as poor (16% in controls). Sexual function was good in 66% (controls: 74%) and poor in 10% (controls: 12%). Mental function was assessed to be good in 92% (controls: 82%). The majority of patients felt comfortable with their physical, sexual and mental capabilities. This was independent from the immunosuppressive regimen.

Cyclosporine↗
PubMed1997

A single and multiple dose bioavailability study with carbamazepine 400 mg retard tablets with reference to enzyme autoinduction and circadian time differences.

UNLABELLED: Both single and multiple dose bioequivalence studies are required to assess the quality of modified release formulations of drugs. In bioequivalence studies of drugs with enzyme autoinducing properties such as carbamazepine (CBZ), the standard multiple dose study design must be modified to guarantee equivalence of drug elimination. This problem was considered with regard to carbamazepine 400 retard AWD (test) whose bioavailability relative to a listed reference (Tegretal 400 retard) was studied in 2 randomized, open, crossover studies both with 18 healthy volunteers of Caucasian origin (20-36 years, 61.5-92 kg, 172-195 cm). The single dose study was done with 400 mg CBZ. Serum concentration time profiles of CBZ and its active metabolite CBZ-10,11-epoxide were determined until 144 h after administration. The multiple dose study was performed with 400 mg CBZ b.i.d. for 15 days (first 2 days: 200 mg b.i.d.) followed by a 7-day study with the alternative investigational product. 24-hour serum concentration time profiles of CBZ and its metabolite were measured on days 15 and 22 of the study. The quantitative drug analysis was done with an HPLC method the quality of which fulfilled the requirements of bioequivalence studies. Test was considered bioequivalent to reference with regard to the extent of absorption, if the 90% confidence intervals of the AUC0-infinity ratio (single dose) and AUC0-24h ratio (multiple dose) were within the range of 0.80-1.25, and with regard to rate of absorption if the 90% confidence intervals of the Cmax/AUC ratio (single dose) or AUCF0-24h ratio were within 0.70-1.43. The point estimators (90% confidence limits) of the AUC ratio (test/reference) of CBZ were 0.979 (0.94, 1.02) for the single and 1.01 (0.947, 1.076) for the multiple dose comparison. The point estimator (90% confidence limits) of the Cmax/AUC ratio was 0.989 (0.959, 1.020) and of the AUCF0-24h ratio 1.066 (0.937, 1.212). There were no circadian time differences in any pharmacokinetic parameter. IN CONCLUSION: Carbamazepine 400 retard AWD tablets were bioequivalent to reference with regard to extent and rate of absorption after both single and multiple dose administration.

Adult↗
PubMed1996

Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation in patients with schizophrenia and major depression.

Debrisoquine 4-hydroxylation and sulphamethazine N-acetylation phenotypes were determined in 115 Czech drug-free in-patients with schizophrenia (n = 64) or major depressive disorder (n = 51). These data were compared with a control group of 321 healthy volunteers from the North-East German area of Greifswald. The distribution of debrisoquine hydroxylator phenotypes was almost identical in patients and healthy controls. Thus, there were 8.7% (95% CI 5.4-12.0%) of poor metabolizers (PM) among patients while 8.7% (95% CI 23.6-13.8%) PM among the control group. The prevalences of PM amongst patients with chronic schizophrenia and major depression were 10.9% (95% CI 4.5-21.3%) and 5.9% (95% CI 1.24-16.3%), respectively (chi 2 schizophrenics vs control = 0.315, NS; chi 2 depressive patients vs control = 0.450, NS). However, within the group of EM patients there was a significant (P < 0.01) shift towards higher debrisoquine metabolic ratios, reflecting a lower hydroxylation capacity in EM patients compared with EM healthy controls. The proportion of slow acetylators (SA) was 60.0% (95% CI 51.0-68.9%) in the entire group of psychiatric patients and 57.5% (95% CI 52.1-62.9%) in the control group (chi 2 all patients vs control = 0.195, NS). Furthermore, there were no significant differences in the prevalence of the SA phenotype between controls and schizophrenics or patients with major depression. Although the results of this modest study were negative, the presence of subtle differences in the metabolic capacity between psychiatric patients and a healthy population cannot be ruled out.

Acetylation↗
PubMed1995

Effects of streptolysin O, picibanil (OK 432) and interferon alpha 2A on cytochrome P-450-dependent monooxygenases and arylamine N-acetyltransferase in rat liver.

Streptolysin O, a thiol-activated exotoxin from group A beta-haemolytic streptococci, caused a dose-dependent depression of aniline hydroxylase, aminopyrine N-demethylase and ethylmorphine N-demethylase activities when added into the hepatic microsomal mixtures from male rats at concentrations 0.02-0.4 HU/mL in vitro. The activities of 7-ethoxycoumarin O-deethylase, 7-ethylresorufin O-deethylase and 7-pentylresorufin O-depentylase were not altered with the used concentrations of the toxin. Specific antibody against haemolytic action of streptolysin O added to incubation mixtures in vitro was not able to protect streptolysin-sensitive monooxygenases from the inhibition. The addition of streptolysin O (0.01-0.8 HU/mL) into the cytosol-containing medium did not significantly influence the activity of procainamide N-acetyltransferase. Immunomodulators picibanil (OK 432) and human recombinant interferon alpha 2A which are known to suppress oxidative metabolism in vivo in humans and animals, were without effect either on the cytochrome P-450-dependent monooxygenases or on the N-acetyltransferase activity when administered in vitro at the doses real in their clinical application (0.001-0.1 KE/mL of picibanil and 10-500 U/mL of alpha-interferon).

Animals↗
PubMed1995

[Differential value of various vital stains of corneal endothelium].

Specular microscopy shows the integrity of the endothelial cell pattern, and vital staining methods allow the evaluation of endothelial viability. Dyes commonly used such as trypan blue enter the cells passively through the disturbed membrane. The uptake of fluorescein diacetate (FDA) is an active process. To compare the efficiency of the two methods we performed double stainings and examined the results. Pig cornea endothelium was stained by both trypan blue and FDA and vital and non-vital cells were compared. More non-vital cells were stained by FDA than by trypan blue, indicating that cells with membranes that are not permeable by trypan blue cannot metabolize FDA. This fact is important where estimating the endothelial viability of donor corneas.

Animals↗