[Diagnostic and therapeutic management of helicobacter pylori: a survey among German gastroenterologists in private practice]. / Diagnostisches und therapeutisches Management der Helicobacter-pylori-Infektion: eine Umfrage unter niedergelassener Gastroenterologen in Deutschland.

Purpose: The acceptance and realization of clinical guidelines in daily routine practice is unknown. The aim of this study was to evaluate the behaviour of private gastroenterologists in Germany with respect to the diagnostic and therapeutic management of H. pylori infection in times of increasing antibiotic resistance. Methods: Between 12/2014 and 02/2015 a standardized questionnaire with 19 multiple choice questions were sent to 1507 private gastroenterologists in Germany. The data were electronically captured and analyzed using SurveyMonkey. Results: The response rate was 36 % (540 questionnaires). 65 % of responders prescribe first line therapy by themselves and mainly use standard triple therapies. In patients with intolerance to penicillin, 81 % prescribe Italian triple therapy and 19 % prescribe bismuth quadruple therapy. Risk factors for primary clarithromycin resistance (migrational background, previous macrolide exposure) are routinely assessed by only a minority of responders (22 % and 17 %, respectively). Forty-one percent of responders perform eradication control by themselves mainly using a 13C urea breath test (54 %). In second line therapy, 42 % are prescribing bismuth quadruple therapy and 24 % fluoroquinolone triple therapy. After second line therapy, 58 % of responders are performing eradication control by themselves. Of those, 70 % always take biopsies for antibiotic susceptibility testing. Conclusions: The results of our survey suggest that most private gastroenterologists in Germany adhere to current guidelines for H. pylori management; however, some relevant deviations seem to exist. Our data might be useful for further developments of clinical guidelines and their communication among the medical community.

Magnetic particle hyperthermia: Néel relaxation in magnetic nanoparticles under circularly polarized field.

The mechanism of magnetization reversal in single-domain ferromagnetic particles is of interest in many applications, in most of which losses must be minimized. In cancer therapy by hyperthermia the opposite requirement prevails: the specific loss power should be maximized. Of the mechanisms of dissipation, here we study the effect of Néel relaxation on magnetic nanoparticles unable to move or rotate and compare the losses in linearly and circularly polarized fields. We present exact analytical solutions of the Landau-Lifshitz equation as derived from the Gilbert equation and use the calculated time-dependent magnetizations to find the energy loss per cycle. In frequencies lower than the Larmor frequency, linear polarization is found to be the better source of heat power, at high frequencies (beyond the Larmor frequency) circular polarization is preferable.

Is there any connection between the presence of kidney stones in primary hyperparathyroidism and the location of an underlying adenoma?

The majority of the patients with primary hyperparathyroidism (pHPT) recurrently produce kidney stones, while the rest have other clinical manifestations. The aim of this study was to examine the possibility of an association between the presence of kidney stones and the location of an underlying adenoma. This was a retrospective evaluation of the records of 91 patients (10 males, 81 females, mean age: 61.9 years [20 - 70 yrs]) operated for primary hyperparathyroidism between 1995 and 2000. One patient was excluded due to carcinoma. Kidney stones were found in 55 cases and other clinical symptoms in 35 cases. In 50 of the 55 patients (91 %) with kidney stones, the adenoma was located in the left inferior parathyroid gland (chi2 = 67.5, p < 0.00,001), while in 24 of the 35 patients (69 %) without kidney stones, the adenoma was in the right inferior parathyroid gland (chi2 = 43.9, p < 0.0001). These results suggest that the location of the adenoma may influence the presence of kidney stones in pHPT. It is proposed that the biologic effects of parathyroid hormone could differ depending on which of the four parathyroid glands it was secreted in, or the four glands may produce different biologically active fragments.

Anti-inflammatory effect and soft properties of etiprednol dicloacetate (BNP-166), a new, anti-asthmatic steroid.

In vitro and in vivo anti-inflammatory properties and soft characteristics of etiprednol dicloacetate (BNP-166) a new steroid, which has been developed for the treatment of asthma, were investigated in this study. The compound effectively decreased cytokine production in lipopolysaccharide stimulated lymphocytes and attenuated lectin-induced proliferation of blood mononuclear cells in tissue culture. In an animal model of allergen sensitized and challenged Brown Norway rats, using topical treatment, etiprednol dicloacetate substantially attenuated the extent of allergen induced bronchoalveolar fluid eosinophilia. At every examined parameter its pharmacological effects were comparable to those of budesonide. By means of in vitro biological and analytical methods the soft character of BNP-166 was also investigated. The anti-inflammatory effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of serum components, present in the assay. This loss of activity was most likely the result of the fast metabolism of etiprednol dicloacetate, which in the presence of sera could have been demonstrated by LC/MS/MS. Our data indicate that the significant local effect of the compound will very likely be accompanied with a drastically reduced systemic activity indicating an encouraging selectivity of the pharmacological action of etiprednol dicloacetate.

Decreased bone density, elevated serum osteoprotegerin, and beta-cross-laps in Wilson disease.

Osteopathia has been reported in Wilson disease (WD), but bone density has not been measured; therefore, we performed bone mineral density (BMD), bone mineral content (BMC), and quantitative bone ultrasound (QUS) assessments, as well as measured the serum levels of osteocalcin (OCN), beta-cross-laps (beta-CTx's), and the recently discovered osteoprotegerin (OPG) and its ligand RANKL to investigate the underlying mechanism of osseous disorders. Serum OCN, beta-CTx, OPG, and RANKL levels were measured by ELISA in 21 WD patients and in 20 age- and gender-matched healthy subjects. BMD, BMC, and QUS parameters were also determined. Osteoporosis was present in 9/21 (43%) WD patients. Abnormal QUS parameters were found in 7 (33%) of the patients. Although serum OCN levels were similar in patients and controls (29.93 +/- 24.65 mg/ml vs. 29.84 +/- 6.89 mg/ml), beta-CTx and OPG levels were significantly increased in WD compared with the healthy controls (625.4 +/- 312.3 pg/ml vs. 423.6 +/- 144.3 pg/ml and p = 0.022 and 7.2 +/- 3.4 pM vs. 3.5 +/- 1.0 pM and p < 0.001, respectively). No difference was observed in the RANKL level. There was a positive correlation between OCN and beta-CTx (r = 0.55; p = 0.01). We proved high occurrence of osteoporosis in WD. Negative bone remodeling balance is a consequence of increased bone resorption, which is indicated by elevated beta-CTx. The novel finding of elevated serum OPG may reflect a compensatory reaction to enhanced osteoclast activity, despite the normal OCN level.

Pharmacokinetic study on a new antiischaemic agent (BRLP-42).

In the present study the pharmacokinetics of BRLP-42--a new antiischaemic agent--was investigated in dogs and rats. Plasma concentrations were measured by HPLC. After intravenous application the curves can be characterized by a two-compartment open pharmacokinetic model. The central volume of distribution (Vcentr.) is large (1.07 +/- 0.14 l/kg in dogs and 2.74 l/kg in rats), the first elimination half-life (t1/2 alpha) is 5.47 +/- 1.67 min in dogs and 13.7 min in rats. These facts indicate rapid and large tissue distribution. The excretion and/or metabolic elimination of BRLP-42 resulted in short second elimination half-life (t1/2 beta = 41.45 +/- 2.34 min in dogs and 43.8 min in rats). After oral application high individual variability can be seen. This fact may be due to the different rate and/or extent of absorption process. The plasma level curves can be characterized by a one-compartment open pharmacokinetic model. The absorption seems to conceal the distribution phase of the kinetic curve. The absorption half-life was short (t1/2a = 17.36 +/- 5.90 min in dogs and 2.7 min in rats). The bioavailability was 40 +/- 8% in dogs and 28% in rats. The elimination half-life (t1/2e = 28.77 +/- 0.88 min in dogs and 30.1 min in rats) is connected dominantly with metabolic elimination and/or excretion of BRLP-42. In the cases of intravenous as well as oral administrations the plasma concentrations decreased under the limit of quantitation by 4-6 hours in dogs and 4 hours in rats after treatments.

[Pharmacokinetic studies of epervudine in rats using HPLC]. / Epervudine farmakokinetikai vizsgálata HPLC módszerrel patkányokon.

Pharmacokinetic properties of active substance of Hevizos ointment (Epervudine) were studied in rats after intravenous, oral and dermal applications. The animals received 10 mg/kg of Epervudine intravenously and orally. For checking of dermal absorption 220 mg of ointment (containing 0.8% of Epervudine) was applied. An HPLC method was developed for determination of Epervudine concentrations in serum. The method meets the requirements of precision and accuracy of the kinetic measurements (i.e. CV% is less than 20%) within the concentration range of 50-10,000 ng/ml. The mean serum concentration-time curve after i.v. administration can be characterized by a two-compartment open pharmacokinetic model. The first and second elimination half-lives (t1/2 alpha and t1/2 beta) are 0.14 and 0.31 hours, respectively. These values indicate fast distribution and elimination of compound studied. In the case of oral administration the absorption process conceals the fast distribution, so the mean serum concentration-time curve can be characterized by a one-compartment open pharmacokinetic model. The absorption of Epervudine starts practically prompt. The absorption half-life (t1/2a) is 0.11 hours. Highest serum concentrations were measured from 20 to 90 minutes after treatment. The elimination half-life (t1/2e) is 1.53 hours. The ratio of areas under serum level curves following oral and intravenous administration proves a good bioavailability (90%) of Epervudine. After dermal application Epervudine does not absorb.

Pharmacokinetic and metabolism studies on girisopam by chromatographic and spectrometric methods in humans.

Girisopam possesses selective anxiolytic action without muscle relaxant and anticonvulsive activity. After a 100-mg oral dose of 14C-labelled girisopam to seven male subjects, the mean recovery of 14C radioactivity was 51% in urine and 33% in faeces. A high-performance liquid chromatographic method has been developed for studying girisopam in single-dose pharmacokinetic studies. The serum extract was chromatographed on a normal-phase column using a mobile phase of hexane-ethanol-diethyl ether (66:9:25, v/v) and ultraviolet detection at 235 nm. The recovery was 60% and the detection limit was 3 ng/ml, using 1 ml of serum. After a 20-min delay, girisopam is rapidly absorbed. After reaching a mean serum level of 178 ng/ml at a mean time of 2.0 h, the serum concentration of girisopam decreased with a mean elimination half-time of 22.2 h. The metabolites were separated by high-performance liquid chromatography, radio thin-layer chromatography and gas chromatography. Their structures were determined by liquid chromatography-mass spectrometry, mass spectrometry and gas chromatography-mass spectrometry. Their chemical structures were confirmed by comparison with synthesized reference compounds. The major urinary metabolites were 7-demethylgirisopam (I), 4'-hydroxygirisopam (II) and 4-hydroxymethyl-4-demethylgirisopam (III), which were in conjugated form, and 4-carboxy-4-demethylgirisopam (V), a compound with an open-chain structure (VII) and traces of 4-demethyl-4-oxogirisopam (VIII) and 4-hydroxymethyl-4-demethylgirisopam (III), which were in non-conjugated form. The metabolic profile in the serum consisted predominantly of the glucuronides of I, II and III. The non-conjugated metabolites were the metabolite with the open-chain structure (VII), III and V. Besides the parent compound, the faeces sample contained conjugates of I and II.

[In vivo bioequivalence study of Sulpirid (GYKI-Alkaloida) and Dogmatil fort (Delagrange) 200 mg sulpiride tablets in healthy volunteers]. / A Sulpirid (GYKI-Alkaloida) és a Dogmatil fort (Delagrange) 200 mg sulpirid hatóanyagtartalmú tabletták in vivo bioekvivalencia vizsgálata egészséges önkénteseken.

A single-dose, "crossover" bioequivalence study was conducted in healthy volunteers by comparing sulpiride serum levels after oral administration of the Test Product Sulpiride (200 mg) (GYKI-Alkaloida) in fasting subjects with those produced after oral administration of a marketed reference product (200 mg) (Delagrange Co., France). Statistical comparisons of Cmax, Tmax and AUC0-infinity have been performed utilizing ANOVA with subject, group, subject within group, period and product as sources of variance. No significant differences between the Test Drug and the Reference Drug considering the pharmacokinetic parameters Cmax, Tmax and AUC0-infinity were found. The 95% confidence intervals were as follows: AUC0-infinity: -20.46% and 31.19%, Cmax: -28.05% and 26.65% and Tmax: -43.53% and 20.67%. In the study for the analysis of Sulpiride a specific HPLC procedure with uv detection (lambda = 228 nm) and an internal standard were applied according to P. Nicolas et al. with modification. Sulpiride levels in serum reached a maximum at 4.4 hr +/- 1.5 (S.D.) following administration of Sulpiride tablet and at 5.0 hr +/- 0.8 (S.D.) after Dogmatil fort tablet. The maximal serum concentrations were 506.1 ng/ml +/- 87.2 (S.D.) and 509.1 ng/ml +/- 101.9 (S.D.) for Sulpiride and Dogmatil fort, respectively. The half-life of Sulpiride in serum was 9.9 hr +/- 1.3 (S.D.) following dosing with Dogmatil fort tablet and 12.2 hr +/- 3.0 (S.D.) following dosing with Sulpiride tablet.