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Biomedical subjects

K U Petersen

Publications and source records attributed to K U Petersen.

At least 19 recordsLinked to original sources
PubMed2005

[MR-sialography: optimisation and evaluation of an ultra-fast sequence in parallel acquisition technique and different functional conditions of salivary glands].

PURPOSE: To optimise a fast sequence for MR-sialography and to compare a parallel and non-parallel acquisition technique. Additionally, the effect of oral stimulation regarding the image quality was evaluated. MATERIAL AND METHODS: All examinations were performed by using a 1.5-T superconducting system. After developing a sufficient sequence for MR-sialography, a single-shot turbo-spin-echo sequence (ss-TSE) with an acquisition time of 2.8 sec was used in transverse and oblique sagittal orientation in 27 healthy volunteers. All images were performed with and without parallel imaging technique. The assessment of the ductal system of the submandibular and parotid gland was performed using a 1 to 5 visual scale for each side separately. Images were evaluated by four independent experienced radiologists. For statistical evaluation, an ANOVA with post-hoc comparisons was used with an overall two-tailed significance level of P =.05. For evaluation of interobserver variability, an intraclass correlation was computed and correlation >.08 was determined to indicate a high correlation. RESULTS: All parts of salivary excretal ducts could be visualised in all volunteers, with an overall rating for all ducts of 2.26 (SD +/- 1.09). Between the four observers a high correlation could be obtained with an intraclass correlation of 0.9475. A significant influence regarding the slice angulations could not be obtained (p = 0.74). In all healthy volunteers the visibility of excretory ducts improved significantly after oral application of a Sialogogum (p < 0.001; eta (2) = 0.049). The use of a parallel imaging technique did not lead to an improvement of visualisation, showing a significant loss of image quality compared to an acquisition technique without parallel imaging (p < 0.001; eta (2) = 0.013). CONCLUSION: The optimised ss-TSE MR-sialography seems to be a fast and sufficient technique for visualisation of excretory ducts of the main salivary glands, with no elaborate post-processing needed. To improve results of MR-sialography, it is reasonable to use an oral Sialogogum.

Computing Methodologies↗
PubMed2005

Mental disorders in current and former heavy ecstasy (MDMA) users.

BACKGROUND: Ecstasy use has often been found to be associated with psychopathology, yet this research has so far been based largely on subjective symptom ratings. AIMS: To investigate whether ecstasy users suffered from long-term psychopathological consequences. MEASUREMENTS: We compared the prevalence of Diagnostic and Statistical Manual version IV (DSM-IV) mental disorders in 30 current and 29 former ecstasy users, 29 polydrug and 30 drug-naive controls. Groups were approximately matched by age, gender and level of education. The current ecstasy users reported a life-time dose of an average of 821 and the former ecstasy users of 768 ecstasy tablets. FINDINGS: Ecstasy users did not significantly differ from controls in the prevalence of mental disorders, except those related to substance use. Substance-induced affective, anxiety and cognitive disorders occurred more frequently among ecstasy users than polydrug controls. The life-time prevalence of ecstasy dependence amounted to 73% in the ecstasy user groups. More than half of the former ecstasy users and nearly half of the current ecstasy users met the criteria of substance-induced cognitive disorders at the time of testing. Logistic regression analyses showed the estimated life-time doses of ecstasy to be predictive of cognitive disorders, both current and life-time. CONCLUSIONS: The motivation for ecstasy use is not likely to be self-medication of pre-existing depressive or anxiety disorders as these did not occur more frequently in the ecstasy users than in control groups or in the general population. Cognitive disorders still present after over 5 months of ecstasy abstinence may well be functional consequences of serotonergic neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA).

Adult↗
PubMed2004

[AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related disorders].

Actually, guidelines for treatment of substance-related disorders were written under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines is the description of the current scientifically proven and evidence-based medicine in addiction to derive recommendations to therapy. In this context, the guideline for treatment of cocaine-, amphetamine-, ecstasy-, and halluzinogen-related disorders is introduced.

Adult↗
PubMed2003

A summary of Food and Drug Administration-reported adverse events and drug interactions occurring during therapy with omeprazole, lansoprazole and pantoprazole.

BACKGROUND: Pantoprazole is claimed to have a lower potential for drug interaction than other proton pump inhibitors. AIM: To estimate the frequency of adverse events and drug interactions reported to the Food and Drug Administration in patients receiving omeprazole, lansoprazole or pantoprazole. METHODS: The study involved a search of the Food and Drug Administration's database for adverse events and drug interactions with omeprazole, lansoprazole or pantoprazole as primary or secondary suspect drug. An estimate of the amount of drug dispensed during the adverse event collection period (from US drug launch) was obtained from the International Medical Statistics health database. RESULTS: Of the suspected drug interactions recorded, vitamin K antagonist interactions, although rare, were the most common. The frequency of vitamin K antagonist interactions was 0.09 per million packages for omeprazole and 0.11 per million packages for lansoprazole and pantoprazole. Interactions with benzodiazepines or phenytoin were even rarer, being reported in less than 10 patients on each proton pump inhibitor. CONCLUSION: The frequency of reported drug interactions was low for omeprazole, lansoprazole and pantoprazole and vitamin K antagonist interactions were by far the most common. These potentially important drug interactions, although rare, were no less frequent on pantoprazole than on omeprazole or lansoprazole, suggesting a class effect.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

[Original brands and generic preparations].

BACKGROUND: Modern guidelines of drug approval aim at interchangeability of drugs containing the same active ingredients. Therapeutic equivalence of original and generic drugs is assumed as soon as bioequivalence is documented. For this to be accepted, first, pharmaceutical equivalence must prevail (the same amount of active substances in the same dosage forms) and, second, differences in bioavailabilities must not exceed certain limits. Drastic deviations from the original--not infrequent in the past--have become rare under the new sets of rules. CURRENT RELEVANCE: However, there is still room for sometimes stunning discrepancies between approved drugs, since the current procedures--mainly for economic reasons--do not cover some potentially relevant aspects: Usually, studies are performed on young, healthy, mostly male volunteers; possible effects of meals on bioavailability are not investigated and, after approval of a drug, maintenance of attested quality--as with all manufacturers--is not monitored. Moreover, the tolerated deviations from the bioavailability of the original drug are quite large; with certain substances, a change from the generic drug with the lowest bioavailability to that with the highest could mean transition from low efficacy to a toxic dose level. Documented examples include carbamazepine, phenytoin, levothyroxin, verapamil, and aspirin. CONCLUSIONS: In conclusion, even today's sophisticated rules do not suffice to cover all eventualities. In particular, drugs with a narrow therapeutic range require close scrutiny in product selection. Pertinent are drug documentation as well as the distinguishing features of the respective manufacturers, mainly scientific support and record of product reliability. Besides the sometimes insufficient official documentation, the internet has been gaining importance as a source of information.

Biological Availability↗
PubMed1995

Review article: omeprazole and the cytochrome P450 system.

Enzymes of the cytochrome P450 superfamily play a key role in xenobiotic metabolism. Their properties and significance are discussed with particular reference to interactions with the H+,K(+)-ATPase blocker, omeprazole. Such interactions include both inhibitory (subfamily 2C) and inducing effects (subfamily 1A). Delayed metabolic elimination of diazepam, warfarin, carbamazepin and phenytoin is probably due to omeprazole competition for the concerned isoform of subfamily 2C; however, these effects are modest to negligible in magnitude and, for phenytoin, not consistently reproducible. Also, induction of subfamily 1A is only minor as assessed from the resultant changes in N-3-demethylation of caffeine, a reaction specific to this subfamily. Concerns about a possible activation of procarcinogens that might arise from subfamily 1A induction appear ill-founded given the fact that cruciferous vegetables such as broccoli and Brussels sprouts are potent inducers, but rather seem to lower the incidence of certain types of cancer. Likewise, the idea that the toxicity of acetaminophen might increase upon subfamily 1A induction appears far-fetched, mainly because much stronger inducers of subfamily 1A (cigarette smoke and charcoaled beef) are unable to alter acetaminophen metabolism.

Acetaminophen↗
PubMed1993

Electrogenic bicarbonate secretion in gallbladder: induction by barium via neuronal, possibly VIP-ergic pathways.

In guinea-pig gallbladder epithelium, cAMP converts electroneutral HCO3- secretion into an electrogenic process. The effects of blood side Ba2+ (5 mmol/l) on HCO3- transport were investigated in vitro, using pH-stat and voltage clamp techniques to determine unidirectional fluxes of HCO3- and transepithelial electrical characteristics. Serosal, not mucosal addition of Ba2+ elevated short-circuit current (Isc), transepithelial potential difference, and tissue conductance; it inhibited the absorptive HCO3- flux while leaving the secretory flux unchanged. The Isc effect of Ba2+ was inhibited or prevented by tetrodotoxin; D- and L-propranolol; the Cl- channel blocker 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; the intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)ocytl ester; noradrenaline, by a yohimbine-sensitive action; somatostatin; HCO3(-)-free solutions. Thus Ba2+ appeared to release a neurotransmitter that gives rise to cAMP synthesis sufficient to turn part of electroneutral HCO3- secretion electrogenic. In a search for the involved signalling pathways, the H1-receptor antagonist, cetirizine, largely and hexamethonium, atropine, atenolol, indomethacin, and trifluoperazine entirely failed to antagonize the Isc effect of Ba2+. Similarly, carbachol, dobutamine, salbutamol, and serotonin were unable to mimic the action of Ba2+ and Isc effects of histamine were small and short-lived. By contrast, vasoactive intestinal peptide (VIP; 3 x 10(-7) mol/l) completely transformed HCO3- secretion into an electrogenic process. The VIP receptor antagonist (4Cl-DPhe6, Leu17) VIP, delayed and reduced the Isc responses to Ba2+ and VIP. As guinea-pig gallbladder epithelial cells possess cAMP-coupled VIP receptors close to VIPergic neurons, Ba2+ is likely to act by releasing VIP from neural terminals.

Alprostadil↗
PubMed1993

HCO3- reduces paracellular permeability of guinea pig duodenal mucosa by a Ca2+ (prostaglandin)-dependent action.

The mechanism of HCO3(-)-induced decrease in electrical conductance (Gt) of guinea pig duodenal mucosa was investigated in vitro. Gt and unidirectional fluxes of mannitol (M), Na+, and Cl- were straightly correlated. In the presence of HCO3- (20 mM), elevating the bath concentration of Ca2+ from 0 to 1.2 mM caused decreases in Gt and Na+ fluxes by approximately 30%. Smaller reductions were found in the absence of HCO-3. With the addition of Ca2+, Gt and unidirectional fluxes were lower with than without HCO3-. In the latter condition, PM/PNa, PM/PCl, and PNa/PCl (P is permeability) were close or equal to ratios predictable from free solution diffusion coefficients; with HCO3-, ratios became different or more different and PM/PNa was reduced. Straightly correlated were conductivities of six differently composed HCO3(-)-free salines and Gt of tissues bathed therein. This correlation did not embrace HCO3- Ringer. The Gt effect of Ca2+ (HCO3- present) was mimicked by prostaglandin E2 and reduced (by approximately 40%) by Ca2+ channel blockers (diltiazem, gallopamil), cyclooxygenase inhibitors (meclofenamate, diclofenac), cytochalasin D, and trifluoperazine. We conclude that without HCO3-, paracellular solute flow occurs mainly via structures resembling a free-solution shunt; HCO3-, through an action made more efficient by Ca(2+)-mediated prostaglandin synthesis and possibly involving microfilaments, strengthens a discriminatory barrier.

Animals↗
PubMed1993

Secretin and somatostatin as modulators of electrolyte transport in guinea pig gallbladder epithelium.

Effects of secretin and somatostatin on electrolyte transport by guinea pig gallbladder epithelium were investigated in vitro. Tissues were mounted in Ussing-type chambers and continuously short-circuited to measure tissue conductance, short-circuit current (Isc) and transepithelial voltage. Unidirectional fluxes (from mucosa to serosa: Jms; from serosa to mucosa: Jsm) of Na+ and Cl- were determined simultaneously by using tracer techniques and those of HCO3- by pH-stat titration. Serosal addition of secretin caused concentration-dependent increases in tissue conductance, Isc and (lumen-negative) transepithelial voltage. At 1.3 x 10(-8) M, secretin raised net HCO3- secretion by 1.5 mumol/cm2/hr, due to inhibition of Jms (from approximately 1.2 to approximately 0.7 mumol/cm2/hr) and stimulation of Jsm (from approximately 3.7 to approximately 4.7 mumol/cm2/hr). The associated increase in Isc by approximately 3.8 mumol/cm2/hr (up from approximately 0.5 mumol/cm2/hr) was not different from net HCO3-secretion (approximately 4 mumol/cm2/hr). Neither Na+ nor Cl- net fluxes accounted for secretin-induced Isc, both being absorbed at equal rates (Na+: approximately 2.7, down from approximately 4.6 mumol/cm2/hr; Cl-: approximately 2.5, down from approximately 6.4 mumol/cm2/hr). Secretin caused a 10-fold rise of luminal efflux of cyclic AMP that was mitigated by somatostatin, added at 6 x 10(-7) M to the serosal bath. Somatostatin inhibited secretin- and prostaglandin E1-induced Isc, but was ineffective in tissues stimulated with 8-Br-cyclic AMP. It partly reverted the effects of secretin on JmsHCO3 and JsmHCO3, but had no effects in untreated tissues. Our data indicate that secretin converts HCO3-secretion from an electroneutral into an electrogenic process and blocks part of NaCl absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Electrogenic and electroneutral HCO3-secretion by guinea pig gallbladder epithelium: discriminatory abilities of Cl- channel blockers.

The specificity of Cl- channel blockers (including 5-nitro-2-(3-phenylpropylamino-)benzoic acid (NPPB), diphenylamine-carboxylic acid and 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid (MPTC)) was studied in guinea pig gallbladder. This epithelium performs electroneutral HCO3- secretion, due to cell-to-lumen exit by Cl-/HCO3- exchange. At high intracellular cyclic AMP levels [produced by prostaglandin E1, (PGE1)], secretion turns electrogenic, secondary to induction of apical membrane Cl- and HCO3- conductances. Part of HCO3- secretion remains Cl(-)-dependent. Microelectrode, voltage-clamp and pH-stat techniques were used to determine membrane potentials, short-circuit current (Isc) and secretory HCO3- fluxes. With one exception, effective agents (concentration range 10(-5)-10(-4) M, luminal bath) including NPPB and diphenylamine-carboxylic acid inhibited secretory HCO3- fluxes in the presence and absence of PGE1 as well as PGE1-induced Isc. At 10(-4) M, inhibition of Isc was not attenuated by Cl- removal; however, NPPB effects were less at concentrations < 10(-4) M. MPTC (3 x 10(-5)-3 x 10(-4) M) only partly inhibited PGE1-induced Isc, was almost ineffective in Cl(-)-free solutions, and did not affect secretory HCO3- flux under any condition. Effects of NPPB and MPTC were distinct from those of the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxy-phenylhydrazone. This agent (10(-7)-10(-5) M), failed to discriminate between Cl(-)-dependent and -independent Isc. In control tissues, 10(-5) M carboyl cyanide p-trifluoromethoxy-phenylhydrazone practically abolished membrane potentials, whereas 10(-4) M NPPB produced no change.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1993

[Omeprazole and the cytochrome P450 system of the liver].

Enzymes of the cytochrome P450 family play a key role in xenobiotic and thus drug metabolism. The H+,K(+)-ATPase blocker, omeprazole, has been reported to inhibit (subfamily P450IIC) or induce (P450IA) this system. The slower metabolic elimination of diazepam, warfarin und phenytoin is probably due to omeprazole competition for P450IIC; however, this effect was rather negligible in magnitude and not reproducible in each case. Also induction of P450IA was only minor; it resulted in no (theophylline) or trivial changes (caffeine) in elimination of drugs metabolized by this subfamily. Concerns about a possible increase in activation of procarcinogens by P450IA appear illfounded, given the fact that cruciferous vegetables such as broccoli and Brussels sprouts are potent inducers but may rather be associated with a lower incidence of certain types of cancer.

Acetaminophen↗
PubMed1991

Acid-induced increase in electrical conductance of guinea pig duodenal mucosa in vitro. Temporary protection by combined effects of bicarbonate and prostaglandin E2.

Electrical conductance as a sensitive indicator of acid damage has been investigated in guinea pig duodenal mucosa using Ussing-chamber techniques. Reductions of luminal pH from 7.4 to 3.0, 2.3, or 2.0 caused concentration-dependent, progressive increases in conductance, accompanied (pH 2.0) by a continuous increase in hydrogen permeation as determined by pH-stat titration. Increases in conductance and hydrogen flux were related to base-line conductance, with higher values conditioning for a sooner onset and/or more marked elevation. Conductance increases were prevented by timely back titration. Recently, it has been shown that serosal HCO3 reduces conductance by actions dependent on prostaglandins and serosal Na and sensitive to loop diuretics. Here, serosal HCO3 delayed the onset of acid-induced conductance increase by approximately 8 minutes, an effect reduced by omission of serosal Na and during exposure to serosal furosemide (10(-3) mol/L). In the presence of serosal indomethacin (10(-4) mol/L) and HCO3, prostaglandin E2 (10(-6) mol/L serosal bath) delayed the conductance increase. Because HCO3 secretion is negligible in this model, these results indicate effects of HCO3/prostaglandin E2 beyond mere buffering of invading hydrogen. These results are consistent with intracellular actions that tighten the paracellular pathway against acid and thus provide temporary protection from acid injury. In agreement with this view, HCO3 also limited conductance increases after luminal alkalinization by a furosemide-sensitive action.

Animals↗
PubMed1990

Naloxone-insensitive transport effects of loperamide in guinea-pig gallbladder epithelium.

The effects of the antidiarrheal drug, loperamide, on HCO3 and Na transport across guinea-pig gallbladder epithelium were investigated using Ussing-chamber methods. Under basal conditions, mucosal loperamide (10(-4) mol/l) moderately lowered both the absorptive (JHCO3ms) and the secretory HCO3 flux (JHCO3sm) (pH-stat method), most likely by changing paracellular HCO3 flow. Exposure to serosal prostaglandin E1 (10(-6) mol/l) abolished Na absorption and turned HCO3 secretion electrogenic. The associated short-circuit current (Isc) was inhibited by loperamide in a concentration-dependent manner; mucosal addition (threshold at 3 x 10(-6) mol/l) of the drug was more effective. Inhibition of Isc was related to a decrease in JHCO3sm, but exceeded the drop in JHCO3net. The effects on JHCO3sm and Isc were mimicked by [Met5]enkephalin. Naloxone (10(-6) mol/l) was unable to influence the effects of loperamide and [Met5]enkephalin on Isc. There were no pro-absorptive effects of loperamide on unidirectional Na fluxes. We conclude that antisecretory properties of loperamide are solely due to inhibition of electrogenic HCO3 secretion, an effect unrelated to opiate receptor binding.

Alprostadil↗
PubMed1990

Transcellular bicarbonate transport in rabbit gallbladder epithelium: mechanisms and effects of cyclic AMP.

HCO3 permeation through rabbit gallbladder epithelium has been investigated in vitro using voltage-clamp, pH-stat and microelectrode techniques. Mucosa-to-serosa flux of HCO3 (approximately 4.9 mumol cm-2 h-1) was dependent on luminal Na and inhibited by amiloride (1 mmol/l, luminal bath), methazolamide (0.1 mmol/l, both sides), and ouabain (30 mumol/l, serosal bath). Maximal rates of serosa-to-mucosa flux of HCO3 (approximately 2.8 mumol cm-2 h-1) required serosal Na and mucosal Cl. This flux was inhibited by ouabain, 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid (1 mmol/l, serosal bath), and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (0.1 mmol/l, luminal bath). Ineffective were methazolamide (0.1 mmol/l, both sides) and amiloride (1 mmol/l, serosal bath). 8-Br-cAMP (1 mmol/l, serosal bath) largely inhibited the absorptive and moderately stimulated the secretory flux. In tissue conductance, short-circuit current, and transmural voltage prostaglandin E1 (1 mumol/l, serosal bath) and 8-Br-cAMP caused moderate to negligible increases. No significant alterations of apical membrane potential (approximately -65 mV) and the apparent ratio of membrane resistances (Ra/Rb; approximately 1.9) were found. Cell membranes responded to luminal Cl removal mostly with a slow hyperpolarization that was mitigated by 8-Br-cAMP or, in some cases, converted into a small, transient depolarization. Our results are best explained by transcellular HCO3 transport in both directions. In secretion, basolateral HCO3 entry occurs by some form of co-transport with Na, and apical exit by Cl/HCO3 exchange. cAMP opens no major electro-diffusive pathway for apical anion efflux. In absorption, HCO3 import from the lumen into the cell is secondary to cAMP-sensitive Na/H exchange.

8-Bromo Cyclic Adenosine Monophosphate↗