The repeatable method of laparoscopic ovum pick-up (OPU) in sheep: clinical aspects and efficiency of the method.

The aim of the study was to develop new laparoscopic technique for repeated recovery of sheep oocytes. Oocytes were aspirated with specifically designed catheter. It allowed to recover oocytes without ovary damage and to preserve very good quality of recovered oocytes. Fifteen ewes were oocytes donors. Oocytes were collected: one time (group I, n=15), two times (group II, n=15), three times (group III, n=10), four times (group IV, n=5). The endoscope was inserted into the abdominal cavity. Two trockars for putting the manipulators were inserted 15 cm cranial from the udder. Oocytes were collected by aspiration of the follicular fluid from the ovarian follicles. The observed clinical complications were: ovary bleeding and cicatrix at place of needle insertion, the fragmentary adhesion of infundibulum and ovary, adhesions of omentum and peri- toneum near the place where the grasping forceps were inserted and adhesion of ovary and uterus. Ovarian follicles (n=204) were aspirated, 130 (63.8%) oocytes were obtained. Out of 130 obtained oocytes, 112 were qualified for in vitro maturation. The remaining 18 oocytes (13.8%) were rejected due to cytoplasmic changes. The proposed technique allows for the collecting oocytes of good quality that can be used for IMV/IVF techniques and cloning.

Iron-induced luminescence as a method for assessing lipid peroxidation of frozen-thawed goat spermatozoa.

Freezing/thawing procedures induce enhanced reactive oxygen species (ROS) formation in mammalian sperm and these ROS may be a cause for the decrease in sperm function following cryopreservation. In the present study, we used a chemiluminescence method to detect ROS-induced damage in goat spermatozoa. Iron-induced luminescence of fresh and frozen/thawed sperm cells was assessed using a luminometer. It was shown that the freezing/thawing procedure had a significant effect on some luminescence parameters. Semen freezing significantly increased the values of integral, peak max, T.half (rise) and T.max (peak) parameters. A significant correlation was observed between the percentage of motile spermatozoa and integral, peak max and T.half (rise) parameters. In conclusion, the results of the present study indicate that measurement of induced luminescence can be an alternative, sensitive and relatively simple method for assessing the effect of cryopreservation on oxidative damage to spermatozoa.

Theophylline derivatives as potential histamine H3-receptor antagonists.

Previous results of histamine H3-receptors investigations allowed to formulate a general structure of H3-receptor antagonists. According to this model a series of compounds were obtained. As heterocycles they contained a theophylline moiety connected with a polar group (amine, ester, amide, and thiourea function) via an alkyl chain linked by a spacer to a lipophilic residue. The common distance between xanthine moiety and lipophilic rest was a six-link-chain. Selected compounds did not show significant H3-receptor antagonist activity and were weak antagonists at histamine H1-receptors.

4-Aryl-1-piperazinylalkyl derivatives of 1,2,3,4-tetrahydro-beta-carboline ring system. Synthesis and preliminary in vivo studies.

Three series of compounds containing a 4-aryl-1-piperazinylalkyl fragment attached to a different position of the indole (A) or 1,2,3,4-tetrahydro-beta-carboline (B, C) have been prepared. The quantitative relationship between the structure of some derivatives and their sedative effect was found using the Free-Wilson approach.

Structure-activity relationship studies of CNS agents, Part 25. 4,6-di(heteroaryl)-2-(N-methylpiperazino)pyrimidines as new, potent 5-HT2A receptor ligands: a verification of the topographic model.

A series of new 4,6-di(heteroaryl)pyrimidines containing an N-methylpiperazino group (6-13) or an ethylenediamine chain (15-20) in position 2 were synthesized and their 5-HT1A and 5-HT2A receptor affinities were determined. It was shown that the substituent effects on the 5-HT2A affinity are additive and could be described quantitatively. In a behavioral model it was also demonstrated that 6-11 are 5-HT2A receptor antagonists. The molecular modelling results suggested that the distances between the basic nitrogen atom and the two aromatic centers (d1 = 5.2-8.4 A, d2 = 5.7-8.5 A, and d3 = 4.6-7.3 A) define the molecular topography of the 5-HT2A receptor antagonists under study.

[Congenital villous atrophy. Disease picture of congenital chronic diarrhea with poor prognosis]. / Kongenitale Zottenatrophie. Krankheitsbild einer konnatalen chronischen Diarrhö mit infauster Prognose.

We report on a patient with connatal chronic diarrhea. Electron microscopical examination revealed "microvillus inclusion disease", characterized by enterocyte brushborder abnormalities. Differential diagnoses are enteral infection and intolerance to formula protein, rarely disaccharidase deficiency. Therapeutic approaches with glucocorticosteroids, pentagastrin and somatostatin failed, just as using growth factor did. No differentiation of the enterocytes occurred with increasing age. Altogether the prognosis of this disease is very poor.

Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines.

The 5-HT1A and 5-HT2 receptor affinity of 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines 1-8, 10 and 12-15 has been determined. It has been found that the specific 5-HT1A affinity of the protonated form (KiAH+) 2-n-hexyl derivatives 4, 8, 14 and (+)-LSD is of the same order. It has been shown by means of molecular modelling methods that pharmacophores of all the active compounds can adopt a common position at the 5-HT1A receptor model. The model also offers an explanation for the observed stereoselectivity chiral compounds.

Structure-activity relationship studies of CNS agents. Part VIII. Bulk tolerance around the protonation center of 4-substituted 1-(3-chlorophenyl)piperazines at 5-HT1A and 5-HT2 receptors.

The effect of a steric hindrance around the protonation center of the model 4-substituted 1-(3-chlorophenyl)-piperazines 1-9 and 11-14 on their affinity for 5-HT1A and 5-HT2 receptor sites was investigated. Additional evidence for hydrophobic interactions between the N-4 hydrocarbon substituents and 5-HT1A receptors has been presented. However, the hydrophobic forces play a minor role in stabilization of the bioactive complex with 5-HT2 receptors. It has also been found that even bulky substituents around the protonation center of 1-aryl-piperazines are well tolerated at both 5-HT1A and 5-HT2 sites.

Structure-activity relationship studies of central nervous system agents. 5. Effect of the hydrocarbon chain on the affinity of 4-substituted 1-(3-chlorophenyl)piperazines for 5-HT1A receptor site.

The effect of the hydrocarbon chain of the model 4-substituted 1-(3-chlorophenyl)piperazines 12-31 on their affinity for 5-HT1A receptor sites was investigated. It was found that elongation of the 4-n-alkyl chain strongly increases the 5-HT1A affinity of the investigated compounds. The affinity reaches the maximum (Ki = 2.67 nM) for the n-hexyl derivative 20. It was shown that hydrophobic interactions of N-4 substituents of 1-arylpiperazines significantly contribute to their 5-HT1A affinity. The specific binding constant was defined as the receptor affinity of the protonated species of compounds under physiological conditions. The range of Ki(AH+) = 1 - 3 x 10(-11) M is a specific affinity limit of the investigated class of compounds at the 5-HT1A receptor sites.

Synthesis and quantitative structure-activity relationship analysis of 2-(aryl or heteroaryl)quinolin-4-amines, a new class of anti-HIV-1 agents.

Thirty-eight 2-(aryl or heteroaryl)quinolin-4-amines, N,N-disubstituted, N-monosubstituted, and without a substituent at the amino group have been synthesized with use of novel chemistries developed by us recently. Some of these derivatives show anti-HIV-1 activity at a concentration level of 1 microM and low cell toxicity in vitro. The most active and least toxic compounds are derivatives of 2-(3-pyridyl)quinoline. The results of the quantitative structure-activity relationship analyses, including several classical, linear regression correlations and a Free-Wilson approach of de novo model, provide guidelines for the design of new active compounds of this class.

[Is chirality a key to stereoselective drug action?]. / Czy chiralnosc jest kluczem do stereoselektywnego dzialania leków?

The aim of this paper is to analyse examples of stereoselective binding of drugs to receptor sites. Selected examples are also given for the binding of drugs to serum albumin and for stereochemical aspects of drug metabolism.

[Surgical treatment of cholelithiasis]. / Operative Therapie der Cholelithiasis.

The indication for cholecystectomy has undergone a distinct change over the last few years due to the development of endoscopic and medical forms of therapy. The incidence of silent gallstones discovered incidentally has greatly increased owing to the widespread use of ultrasound. While surgery is not indicated in these cases, it is mandatory in acute and chronic septic complications, obstruction of the cystic duct or non-functional gallbladder. In a small number of patients, cholecystolithiasis can be treated with ESWL and chemolitholysis, but most will need surgery. Cholecystectomy is the sole causal therapy. Except in young patients, common bile duct stones are the domain of endoscopic papillotomy, even when the gallbladder is left in situ temporarily or (in high-risk patients) permanently. Here, endoscopy supplements the therapeutic concept even in emergency cases; stone extraction can obviate the need for common bile duct revision. Morbidity and mortality of gallstone surgery increase appreciably with patient age. Early operation is recommended in acute cholecystitis because of the lower morbidity and mortality rates. Present possibilities of individualized therapy require good interdisciplinary cooperation to prevent serious complications.

Technical aid for facilitating emergency endoscopy.

Emergency endoscopy is usually complicated by unfavorable examination conditions. The irrigating capability of the instrument is inadequate. The use of an easy-to-operate volume- and pressure-driven irrigation pump has proved very efficient and safe in the hands of an experienced endoscopist, and helps establish the correct diagnosis or provide proper treatment.

[The effect of mass chest x-ray on early detection of bronchial cancer]. / Der Einfluss der Röntgenreihenuntersuchung auf die Früherkennung des Bronchialkarzinoms.

On 30.6.1983, mass radiographic screening was abandoned despite objections to the effect that it offered the only chance of detecting carcinoma of the lung at an early stage. In a retrospective analysis of our patient material comprising 1.010 patients with bronchial carcinomas seen within the period between 1.1.1980 to 31.12.1986, we investigated the question as to whether these objections might not be justified. Four hundred and thirty-seven patients seen prior to 30.6.1983 were compared with 537 patients examined after this date, on the basis of the following parameters: age - sex - symptomatology - cancer stage - histology - treatment. After stopping mass radiographic screening, an increase in age and symptomatic tumour findings was observed, and thus a shift towards more advanced stages of carcinoma. A relative decrease in the number of squamous cell carcinomas, and a relative increase in the number of adenocarcinomas were observed. All the parameters in the patients identified at mass radiographic screening were comparable with those seen in patients identified incidentally. In comparison with symptomatic patients, those identified by mass radiography screening more frequently presented with earlier tumour stages, and the lesions were more frequently resectable. All in all, over a period of three and one-half years, mass radiographic screening revealed 23.8% of all cancers of the lung, and 36.8% of all resectable lesions. After the abandonment of mass radiographic screening, an increase in more advanced and symptomatic tumours was observed.

New derivatives of amino alcohols with antiarrhythmic activity.

Nine new N-acyl derivatives of 2-amino-1-alcohols and 1-amino-2-alcohols with a potential arrhythmic activity have been obtained. In the preliminary screening 2-[N-(7-theophyllineacetyl)-amino]-2-methyl-1-propanol, 5, was more active in the chloroform-induced arrhythmia than quinidine. Unlike to propranolol and quinidine, compound 5 in doses of 5-30 mg/kg, iv, did not prevent distortions of the cardiac rhythm evoked by adrenaline and strophanthine. When administered at the peak of arrhythmia, it did not abolish disturbances of the cardiac rhythm. Compound 5 had a low toxicity (LD50 = 3000 mg/kg, ip), did not change the control ECG curve, showed no cardiodepressive activity, and had weaker local anesthetic properties than lignocaine.