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Biomedical subjects

K Rudolf

Publications and source records attributed to K Rudolf.

At least 37 records · Page 2Linked to original sources
PubMed1993

Characterization of BIBN 99: a lipophilic and selective muscarinic M2 receptor antagonist.

The present study was designed to characterize the receptor selectivity profile of the novel muscarinic M2 receptor antagonist BIBN 99 (5,11-dihydro-8-chloro-11-[[4-[3-[(2,2-dimethyl-1- oxopentyl)ethylamino]propyl]-1-piperidinyl]acetyl]-6H- pyrido[2,3-b][1,4]benzodiazepin-6-one). In radioligand binding studies BIBN 99 showed high affinity for m2/M2 sites (pKi = 7.52/7.57), intermediate affinity for m4 sites (pKi = 6.76) and low affinity for m1/M1 (pKi = 5.97/6.17), m3/M3 (pKi = 6.11/6.04) and m5 sites (pKi = 5.84). Functional studies in vitro showed BIBN 99 to be a competitive antagonist and to have an 11- to 25-fold higher affinity for M2 receptors than for putative M1 receptors in the rabbit vas deferens or M3 receptors in guinea-pig trachea. In vivo studies revealed that BIBN 99 is able to cross the blood-brain barrier, and although showing an approximately 3-fold higher affinity for M2 binding sites BIBN 99 appeared to be 7- to 18-fold less potent than AF-DX 116 in inhibiting muscarinic agonist or vagally induced bradycardia in rats and guinea-pigs. The results show that BIBN 99 is the first lipophilic muscarinic M2 receptor antagonist to have remarkable M2 versus M1 selectivity (30-fold). In addition, BIBN 99 possesses central nervous system activity and only minor peripheral cardiac effects.

Animals↗
PubMed1993

Therapeutic potential of CNS-active M2 antagonists: novel structures and pharmacology.

Clinical trials with muscarinic agonists or acetylcholine esterase inhibitors for the treatment of Alzheimer's dementia have shown disappointing or equivocal results. An alternative treatment of this disease is the development of drugs which enhance the release of acetylcholine. It is believed, that of the five muscarinic receptor subtypes so far identified in the brain, M2 receptors are located presynaptically in the cortex and hippocampus and upon stimulation inhibit the release of acetylcholine. Based on this hypothesis, we initiated a drug discovery program with the aim of identifying selective and centrally active M2 antagonists which are capable of enhancing cholinergic transmission. These efforts resulted in the successful design and synthesis of novel muscarinic antagonists able to cross the blood brain barrier. Moreover, these compounds show few peripheral effects and possess a superior M2 versus M1 selectivity. The prototype of this novel class of M2 selective compounds, BIBN 99, could be a valuable tool to test the hypothesis that lipophilic M2 antagonists show beneficial effects in the treatment of cognitive disorders.

Animals↗
PubMed1993

Laparoscopic electrocoagulation of the ovarian surface in infertile patients with polycystic ovarian disease.

OBJECTIVE: To assess the endocrinologic and clinical outcome after laparoscopic ovarian electrocautery because of polycystic reaction to ovarian stimulation in anovulatory infertility patients. DESIGN: Between 1986 and 1989, 133 patients with polycystic ovarian disease underwent laparoscopic electrocoagulation of the ovarian surface in an outpatient clinic after conventional ovarian stimulation had led to polycystic reaction. SETTING: All patients were referred to our outpatient clinic affiliated with the university hospital. RESULTS: The reduction of androgen levels and normalization of cycle length were highly significant. The overall pregnancy rate was 70% (73 of 104), ranging from 27% in smokers to 94% in nonsmoking couples. In 26 second-look operations de novo adhesions were found in 26.9% of the patients. CONCLUSION: Laparoscopic coagulation of the ovarian surface is an effective tool to reduce elevated androgen levels and to improve the intraovarian mechanism of selecting a dominant follicle. A postoperative complication may be adhesion formation.

Adult↗
PubMed1990

[The GnRH-TRH double stimulation test before and following surgical removal of uterine leiomyoma].

In seven patients with uterine leiomyomatosis investigated the function of hypothalamic-pituitary-ovarian axis has been with a GnRH-TRH-double stimulation test. The basal levels of estradiol, progesterone, LH, FSH and PRL as well as the pituitary reaction after the stimulation were determined. Three patients had a tendency to a basal hypergonadotropinemia and four patients to hypoprolactinemia. The pituitary reaction following the stimulation does not show any connection between leiomyoma and secretion pattern of the hypothalamic-pituitary-ovarian axis.

Adult↗
PubMed1990

[Type and frequency of gynecological tumors in the Gondar region of Ethiopia].

The present work was done to examine the type and frequency of benign and malignant gynecological tumors in patients treated during the 5 years period from 1982 to 1986 in the Gondar College of Medical Sciences. The different pathohistological findings were compared with the history and chief complaints of the patients. A total number of 208 patients with benign and of 93 patients with malignant tumors could be analyzed. In the group of benign tumors we observed most frequently breast tumors (25.5%), endometrial and cervical polyps (24.5%), and myoma uteri (23.1%). Patients with benign ovarian tumors were treated in 40 (19.2%) cases. In the group of malignant tumors we have seen breast carcinomas (31.2%) and cervical carcinomas (34.4%) most frequently followed by the endometrial (13.0%) and ovarian (11.8%) neoplasms. Comparison with the data of the literature has shown that the mean age of our patients is lower and the number of women with advanced carcinomas is higher than in other reports.

Adolescent↗
PubMed1990

[Heterologous and homologous radioimmunoassays for human prolactin. 1. Development and critical evaluation of the method].

Based on the production of a high specific antibody against ovine prolactin a heterologous prolactin RIA (self proposed method) is introduced. From this work both a homologous and a heterologous system have been developed and used for the PRL-RIA kit production. Substances necessary for setting up the kits, their investigations and applications are described. Statistical considerations about precision, sensitivity, specificity and accuracy show the validity of these heterologous PRL-systems.

Female↗
PubMed1989

[Endometrial findings in long-term treatment with synthetic sex steroids in Turner syndrome].

In 9 patients with Turner's syndrome (karyotype 45/X0) aged from 23 to 50 years (average age 34 years) a curettage was performed. In these women there has been a treatment with mestranol 80 micrograms or ethinylestradiol 50 micrograms and chlormadinome acetate 2 mg as a sequential therapy in a cyclic manner for 5 to 22 years. Additionally in 3 patients a biopsy from the uterine cervix was performed because of abnormal colposcopic findings. Only in one patient an atrophic endometrium was found, whereas in the other patients the endometrium showed a weak proliferation or a slight secretion. Ectasia of the endometrial glands was observed in 4 patients. A hyperplastic endometrium wasn't found in any patient.

Adult↗
PubMed1989

[Applicability of the subrenal capsule assay (SRCA) in primary breast carcinoma].

We have examined the application of the subrenal capsule assay (SRCA) by use of normal immunocompetent (NIC) mice for chemosensitivity testing of primary breast cancers. In 18 out of 20 carcinomas an evaluation was possible. AB mice (10 breast cancers) and B6D2-F1 mice (10 breast cancers) were taken as recipients. Measurement of the size and the histological examination of all transplants were obligatory performed before and after finishing the assay on day 6. By use of AB mice as well as B6D2 mice in each group in 6 out of 9 evaluable cancers occurred a significant growth of the transplanted tissues after 6 days (p less than 0.05). It could be demonstrated by the histological examination that the enlargement was a consequence of the immunological reaction of the NIC mouse to the xenogeneic material. In most cases (76 of 97 used mice) the transplants consisted of inflammation cells only. Vital tumor cells were seen only in few cases (21 of 97 used mice). It is concluded, that the SRCA is not suitable for chemosensitivity testing of human breast cancer, if NIC mice as recipients are used.

Animals↗
PubMed1989

[The importance of growth factors in endocrinology and oncology].

Investigations dealing with the interrelations between peripheral hormones like proteohormones and steroid hormones and local hormones like growth factors in the target cells let us have the knack of the mechanism of action of peripheral hormones. The best known growth factors (EGF, TGF alpha, TGF beta, PDGF, IGF I, IGF II) are mentioned. The interrelation between growth factor and peripheral hormones in the target cell is demonstrated on the example of Estradiol and EGF. The practical consequences of growth factors are pointed out.

Cell Division↗
PubMed1989

Structure-activity relationships and pharmacological profile of selective tricyclic antimuscarinics.

The discovery of the M1-selective receptor antagonist pirenzepine was the impetus for a research project directed towards the development of selective muscarinic antagonists. In the pursuit of this objective, compounds with different selectivity profiles have been found. AF-DX 116 was the first cardioselective antagonist synthesized. Subsequently novel M2 receptor antagonists have been discovered with higher potency and selectivity. Moreover, a pirenzepine-type compound UH-AH 37 has been identified that, in contrast to pirenzepine, shows a higher affinity for ileal than for atrial muscarinic receptors. Among tricyclic muscarinic receptor antagonists three different selectivity profiles have been identified, namely: M1 greater than M3 greater than M2, Msm for pirenzepine; M2 greater than M1 greater than M3, Msm for AF-DX 116, AF-DX 384, AQ-RA 741; and Msm congruent to M1 greater than M2, M3 for UH-AH 37 and its (+) enantiomer.

Antidepressive Agents, Tricyclic↗
PubMed1989

[Evaluation of the subrenal capsule assay (SRCA) in breast cancer using immunocompetent (NIC) mice].

UNLABELLED: To assess the value of subrenal capsule assay (SRCA) for predictive chemo-sensitivity testing in breast cancer 24 primary tumours were examined in normal immunocompetent (NIC; AB- and B6D2-F1-) mice. In 6 cancers the effect of 0.25 mg Prednisolone mous X day (applicated with drinking water) was compared to the control group. Independent of the mice-species a significant increase of the grafts size occurred in 14 of 20 evaluable cancers (p less than 0.05). Histologically the increase of tumour size was caused by infiltrated host cells, only in 22 of 107 (20.6%) grafts vitale tumour cells were detectable. After immunosuppression the increase of the grafts size was significant lower, than in the no treated control group (p less than 0.05). In groups treated with Prednisolone only a thin inflammatory host cell infiltration was observed, but vital tumour cells were only seen in 3 of 29 (10.3%) grafts. CONCLUSION: Using normal immunocompetent mice subrenal capsule assay is not suited for predicting responsiveness of breast cancers to cytostatic drugs.

Animals↗
PubMed1988

[Behavior of the basal and stimulated serum level of thyroid stimulating hormone and determination of thyroxine, thyroxine- binding capacity and free thyroxine index in females with chronic uremia].

In 11 female patients with chronic uraemia at the age of 20 to 47 years (average age 33.1 years) the basal and the thyrotropin releasing hormone-(TRH-) stimulated thyroid gland stimulating hormone-(SH-) secretion were investigated, in addition to this the parameters of the thyroid gland total thyroxin (T4), thyroxin binding capacity (TBC) as well as the free thyroxin-index (FT4-I). In 2 women the investigations were repeated after kidney transplantation. The determination of TSH and T4 was carried out radioimmunologically, TBC was determined according to the principle of the test tube analysis, whereas FT4-I was established by computation. In 9 of the 11 female patients with chronic uraemia a physiological TSH-response behaviour is existing, whereas for T4 deviations from the reference area are to be stated in 7 female patients and for FT4-I in 6 female patients.

Adult↗
PubMed1988

[Behavior of basal and stimulated serum levels of prolactin, growth hormone and gonadotropins in females with chronic uremia].

In 11 female patients with chronic uraemia at the age of 20 to 47 years (average age: 33.1 years) the behaviour of basal and stimulated serum levels of prolactin (PRL), growth hormone (HGH) and gonadotropins (LH, FSH) was investigated. For stimulation of the hormone secretion a sequential test with arginine hydrochloride, gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) was used. In 2 women the investigations were repeated after kidney transplantation. The determination of LH, FSH, PRL and HGH was performed radioimmunologically. The investigations show that in women with chronic uraemia the basal LH-levels in general lie clearly above of those ones of women with biphasic cycles, whereas the FSH-levels are not increased. The LH-response after administration of 25 micrograms GnRH is adequate in 6 women and is absent in 5 women. After kidney transplantation a clear reduction of the basal LH-levels in comparison to the preliminary values is to be established. The increased basal LH-levels are causally made responsible for the disturbances of the menstrual cycle in women with chronic uraemia. For PRL hyper- and normoprolactinaemic as well as hypoprolactinaemic basal levels are found. A connection between the height of the PRL and creatinine levels cannot be proved. Apart from a adequate PRL response to the stimulation with TRH in the individual case this response is inadequate or is absent. The basal HGH-levels are in the area of reference. In all women HGH can adequately be stimulated, whereby the case in question is presumably a so-called paradoxical TRH-effect.

Adult↗
PubMed1988

Coincidence of gonadal dysgenesis and hyperprolactinemia.

It is reported about 4 female patients aged from 3 to 31 years (average age 18 years) with gonadal dysgenesis and hyperprolactinemia. Beside one all these females were not treated with synthetic sexual steroids. In 3 of the 4 patients both hyperprolactinemic and hypergonadotropic serum levels were observed. In one case the gonadotropic serum levels were normal. A stimulation test with GnRH-TRH or arginine-GnRH-TRH, respectively, was performed. In patients with gonadal dysgenesis a change on the area of hypothalamo-hypophyseal axis is supposed to cause the hyperprolactinemia.

Adolescent↗
PubMed1988

[Basal and gonadotropin releasing hormone-stimulated gonadotropin secretion in patients with chronic uremia].

In 11 patients with chronic uremia both the basal and stimulated levels of LH and FSH in serum were determined by RIA. After renal transplantation the investigations were repeated in 2 cases. The basal levels of LH were unphysiologically increased whereas FSH was found in the normal range. The stimulation of LH by GnRH was adequate in 6 patients and in 5 there was no response. As a result of renal transplantation there was a drop of LH in serum. It is supposed that the unphysiological increase of LH in patients with chronic uremia is the cause for the disturbances of the menstrual cycle.

Adult↗