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Biomedical subjects

G Schubert

Publications and source records attributed to G Schubert.

At least 55 records · Page 3Linked to original sources
PubMed1996

A transient role of the kidney in the maintenance of hypertension.

Using the Prague hypertensive rat (PHR), a model derived from the Wistar rat, in which a normotensive parallel, the Prague normotensive rat (PNR), was bred from the same parent pair (so that transplantation of organs between both these parallel rat model lines results in no distinct signs of rejection), we were able to show that hypertension travels with the kidney. Transplantation of a kidney from PHR to a bilaterally nephrectomized (BNX) PNR led to an increase in systolic blood pressure (SBP) in the recipient for 10 weeks after grafting. Similarly, a decrease in SBP was seen in BNX PHR for the same period of time after grafting a kidney from PNR. If, however, the SBP was measured over a longer period of time, because the elevated SBP slowly drops after grafting a kidney from PHR to BNX PNR, it is less than 130 mm Hg in the fourth month and thereafter. If BNX PHR receives a kidney from PNR, the decrease in SBP is permanent, amounting to 126.3 +/- 12.7 mm Hg one year after transplantation. The grafting of a heart from PHR to the abdominal aorta of PNR does not influence SBP. In conclusion, the presence of a kidney from PHR is necessary for the development, but is not sufficient for the maintenance of hypertension. The heart of PHR is not "hypertensogenic" as is the kidney.

Animals↗
PubMed1995

Clinical and urodynamic effects of propiverine in patients suffering from urgency and urge incontinence. A multicentre dose-optimizing study.

The efficacy and tolerability of propiverine hydrochloride (15, off 45, 60 mg/d) were evaluated in the treatment of 185 patients suffering from urgency/urge incontinence in an open, randomized, multicentre parallel-group trial lasting 21 days. The effects on bladder volume and pressure were assessed on the basis of urodynamics and micturition frequency. Subjective adverse reactions were recorded. The bladder capacity and compliance increased and bladder pressure decreased in a dose dependent manner following therapy with 15, 30, 45 and 60 mg/d. In 70% of the patients a decrease in micturition frequency was observed after 15 mg/d, and in 80% after 30 to 60 mg/d. Subjective anticholinergic symptoms were reported by 21, 40 and 28% of the patients following therapy with 30, 45 and 60 mg/d. 15 and 30 mg were the daily doses with the most favourable ratio of efficacy in micturition frequency to tolerability. The results suggest that propiverine is a safe and effective drug for the treatment of urgency and urge incontinence. Individual treatment with an initial dosage of 30 mg/d should be recommended.

Administration, Oral↗
PubMed1994

Intestinal absorption of peptides by coupling to bile acids.

Poor intestinal absorption of peptides greatly limits their use as drugs for the treatment of chronic diseases. Since bile acids are efficiently absorbed by an active, Na(+)-dependent transport system in the ileum of mammals, model peptides of different chain length were attached to the 3-position of modified 3 beta-(omega-amino-alkoxy)-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid. These peptide-bile acid conjugates inhibited Na(+)-dependent [3H]taurocholate uptake into brush-border membrane vesicles isolated from rabbit ileum in a concentration-dependent manner. Furthermore, photoaffinity labeling of the bile acid-binding proteins of M(r) 93,000 and 14,000, identified as the protein components of the ileal Na(+)-dependent bile acid transport system in rabbit ileum (Kramer, W., Girbig, F., Gutjahr, U., Kowalewski, S., Jouvenal, K., Müller, G., Tripier, D., and Wess, G. (1993) J. Biol. Chem. 268, 18035-18046) by the photoreactive taurocholate analogue, (3,3-azo-7 alpha, 12 alpha-dihydroxy-5 beta [7 beta, -12 beta-3H]cholan-24-oyl)-2-aminoethanesulfonic acid, was inhibited by the peptide-bile acid conjugates. In contrast, the parent peptides and amino acids neither had a significant effect on [3H]taurocholate uptake by ileal brush-border membrane vesicles nor on photoaffinity labeling of the ileal bile acid-binding membrane proteins. The inhibitory effect of peptide-bile acid conjugates on [3H]taurocholate transport and photoaffinity labeling of the bile acid-binding proteins in rabbit ileal vesicles decreased with increasing chain length of the attached peptide radical. By in vivo ileum perfusion in anesthetized rats an intestinal absorption of the bile acid conjugate S3744 of the fluorescent oxaprolylpeptide 4-nitrobenzo-2-oxa-1,3-diazol-beta-Ala-Phe-5-Opr-Gly (S1037) and secretion of the intact compound into bile could be demonstrated, whereas the parent peptide S1037 or its t-butylester S4404 were not absorbed. The intestinal absorption of S3744 showed a similar temperature dependence as [3H]taurocholate absorption and was inhibited by the presence of taurocholate indicating a carrier-mediated uptake of S3744 via the ileal bile acid transporter. In conclusion, these results indicate that oligopeptides can be made enterally absorable by coupling to modified bile acid molecules making use of the specific intestinal absorption pathway for bile acids. This finding may be of great importance for the design and development of orally active peptide drugs.

Amino Acid Sequence↗
PubMed1994

[Clinical and urodynamic effects of oral propiverine therapy in neurogenic urinary incontinence. A multicenter study for optimizing dosage].

The efficacy and tolerability of propiverine hydrochloride (in doses of 15, 30, 45 and 60 mg/day) were evaluated in the treatment of 66 patients suffering from neurogenic incontinence for 21 days in an open, randomized, multicentre, parallel-group trial. Evaluation of efficacy was based on changes in cystometry, flow measurements and micturition and that of safety on adverse reactions and blood chemistry. The bladder volume increased and bladder pressure decreased dose dependently; the ratio of the two increased by 0.6, 3.3, 3.8 and 8.1 ml/cm H2O after 15, 30, 45 and 60 mg/day respectively. Some 54% of patients had a decreased micturition frequency after 15 mg/day and about 80% after 30-60 mg/day. At the same time, 8, 35, 12 and 42% of patients had subjective anticholinergic symptoms after therapy with 15, 30, 45 and 60 mg/day, respectively. The results suggest that propiverine is a safe and effective drug for the treatment of neurogenic incontinence. A daily dose of 30 mg propiverine is recommended; individual adjustment of the maintenance dose to 15 or 45 mg/day may be necessary.

Adolescent↗
PubMed1993

The role of the kidney in the development of hypertension: a transplantation study in the Prague hypertensive rat.

It has been shown that genetic hypertension in rats usually "travels with the kidney". To elucidate the mechanism of this phenomenon further, experiments were carried out in the Prague hypertensive (PH) rat, a model of genetic hypertension derived from the Wistar strain, in which a normotensive parallel, the Prague normotensive (PN) rat, was also bred from the same parent pair. Thus, it is possible to transfer organs between both parallels without substantial signs of rejection and without the use of immunosuppressive drugs. Unilateral nephrectomy and transplantation of one kidney between PH and PN rats, did not affect the arterial blood pressure (BP). Transplantation of one kidney from PN rats to bilaterally nephrectomised PH rats normalised the high BP. If a PH rat was left with one original kidney in situ after the transplantation of a "normotensive" kidney, the high BP persisted until the original "hypertensive" kidney was removed. This removal resulted in sustained normalisation of BP. When the development of high BP in the PH rats was prevented for 2 months after weaning by antihypertensive drugs, transplantation of kidneys from these rats to bilaterally nephrectomised PN rats always induced a sustained hypertension in the recipient. These results argue against a role of high-BP-induced damage to the kidney and against an intrinsic increase in the salt-reabsorptive capacity of the tubular epithelium in PH rats. The data support the view that the kidney from PH rats produces a "hypertensinogenic" substance, the secretion of which is genetically determined and is not influenced by the magnitude of the BP.

Animals↗
PubMed1992

Liver-specific drug targeting by coupling to bile acids.

Bile acids are selectively taken up from portal blood into the liver by specific transport systems in the hepatocyte plasma membrane. Therefore, studies were performed to evaluate the potential of bile acids as shuttles to deliver drugs specifically to the liver. The alkylating cytostatic drug chlorambucil and the fluorescent prolyl-4-hydroxylase inhibitor 4-nitrobenzo-2-oxa-1,3-diazol-beta-Ala-Phe-5-oxaproline-Gly were covalently linked via an amide bond to 7 alpha, 12 alpha,-dihydroxy-3 beta- (omega-aminoalkoxy)-5-beta-cholan-24-oic acid. The chlorambucil-bile acid conjugates S 2521, S 2539, S 2567, and S 2576 inhibited Na(+)-dependent [3H]taurocholate uptake in a concentration-dependent manner both into isolated rat hepatocytes and rabbit ileal brush border membrane vesicles, whereas the parent drug chlorambucil showed no significant inhibitory effect. The chlorambucil-bile acid conjugates were able to prevent photoaffinity labeling of bile acid binding proteins in rat hepatocytes by the photolabile [3H]7,7-azo derivative of taurocholic acid indicating their bile acid character. The chlorambucil-bile acid conjugate S 2577 was able to alkylate proteins demonstrating the drug character conserved in the hybrid-molecules. Liver perfusion experiments revealed a secretion profile of the chlorambucil-bile acid conjugate S 2576 into bile very similar to taurocholate compared to chlorambucil which is predominantly excreted by the kidney. 4-Nitrobenzo-2-oxa-1,3-diazol-beta-Ala-Phe-5-oxaproline-Gly- t-butylester (S 4404), a fluorescent peptide inhibitor of prolyl-4-hydroxylase, was not transported in intact form from portal blood into bile in contrast to its bile acid conjugate S 3744; about 25% of the peptide-bile acid conjugate S 3744 was secreted in intact form into bile within 40 min compared with less than 4% of the parent oxaprolylpeptide S 4404. In conclusion, these studies reveal that modified bile acid molecules can be used as "Trojan horses" to deliver a drug molecule specifically into the liver and the biliary system. This offers important pharmacological options for the development of liver-specific drugs.

Affinity Labels↗
PubMed1991

[Enteral anastomosis with the biofragmentable Valtrac ring. A prospective study].

In a prospective study, 150 enteral anastomoses using the new Valtrac biofragmentable anastomosis ring (BAR) are described. The manipulation involved was simple to learn and standardised intestinal anastomoses could be created at various bowel segments. No stenoses or postoperative bleeding occurred, the suture dehiscence rate was low. The use of these rings can be recommended to achieve a high level of standardisation for colon anastomoses and small bowel-colon anastomoses without restriction, whereas for other localisations the number of cases is too small to allow a final assessment to be made.

Anastomosis, Surgical↗
PubMed1990

Development and perspectives of experimental pancreas transplantation in the rat.

Whole organ pancreas transplantation in the rat was first described by Sun Lee in 1972. Since that time the basic technique has been modified in several ways and this model can now be used for a variety of experiments. Various techniques for transplantation and representative results of functional and immunological experiments are summarized.

Animals↗
PubMed1990

[Studies on the occurrence of texture types in calcium oxalate urinary stones].

A review of texture types of calcium oxalate calculi and a pattern of 4 basic texture types was presented. A method of texture classification as a part of the routine polarization microscopy urinary calculus analysis was developed. Thereby a representative material could presented on the distribution of texture types. A connection between pathological urinary parameters and the texture type was demonstrated.

Calcium Oxalate↗
PubMed1989

Molecular mechanics and X-ray crystal structure investigations on conformations of 11 beta substituted 4,9-dien-3-one steroids.

The influence of 11 beta-phenyl substitution upon 4,9-dien-3-one steroid-backbone conformations is calculated by means of the MM2p molecular mechanics scheme. In the case of steroids having a 13 beta configuration, the lowest strain energy is always evaluated for the conformational combination of rings A(inverted) B(normal) while, moreover, the 11 beta substitution increases the relative stability of the conformation A(normal) B(normal) compared to the nonsubstituted compound. Introduction of the 11 beta substituent causes some bowing of the energy-minimum structures in the A-ring region toward the beta side. For 13 alpha configurated steroids, the ring conformations A(inverted) B(normal) C(boat) and A(normal) B(inverted) C(twist/boat) are found to be energetically preferred. Quantitative description of different ring conformations using asymmetry and pseudorotational parameters as well as the comparison of molecular mechanics and available X-ray structure data give an impression of the conformational mobility. Whereas the effect of 11 beta substitution within a given ring conformation is limited, contributions to molecular flexibility can be found in the ability to adopt different basic conformations and in the occupation of near-minimum structures. An X-ray crystal structure analysis of a potential antiprogestational steroid has been performed, and the results are in good agreement with the calculated structure.

Crystallography↗
PubMed1989

[Value of ambulatory clinic-associated stoma therapy, analysis of expenses, success and cost effectiveness from the public economic viewpoint].

A pilot project providing ambulant, hospital-associated stoma care for the affected patients both in the hospital and at home has been in progress in the Kiel/Neumünster area since 1982. An evaluation of the stoma therapist's activities in 1988 and a survey in 1989 demonstrated that patients and family physicians are increasingly accepting the project. Besides a markedly better quality of life, a cautious cost analysis is proved that more than DM 200,000 can be saved annually by avoiding hospitalization and adapting the care system to the needs of the patients.

Ambulatory Care↗
PubMed1988

Urolithiasis associated with urogenital tuberculosis. Clinical and mineralogical aspects.

Of 628 patients with bacteriologically or histologically proven urogenital tuberculosis (UGT) treated from 1960 to 1985. 126 patients (20.1%) had additional urinary tract infection and 66 patients (10.5%) developed urolithiasis. In these 66 patients a simultaneous urinary tract infection occurred in 29 cases (43.9%). Twenty-eight calculi were analyzed by a combined crystal-optical and x-ray-diffraction method. A high incidence of struvite/carbonate apatite calculi (11/28) as well as of calcium phosphate calculi (6/28) was found. The texture of 15 calculi was investigated on thin sections by polarization microscopy and a high concentration of organic material was found in both calcium oxalate and struvite/carbonate apatite calculi probably due to the specific and nonspecific infection with deposition of cell and protein degradation products.

Crystallization↗
PubMed1988

Composition and structure of renal and ureteral calculi in patients under covalitin therapy.

We examined the composition and texture of 53 urinary calculi from patients receiving Covalitin therapy. The texture of the infection stones and of concrements containing mainly apatite showed no changes as compared to concrements from control groups receiving no such therapy. Calcium oxalate stones more often showed a whewellite texture (Type 2) and a less frequent occurrence of weddellite (Type 4) as compared to the control groups. Surface or marginal changes indicating a possible litholysis could not be shown.

Adult↗
PubMed1988

[Need for the differentiation of apatite and carbonate apatite].

With extensive analytical and clinical examinations it is shown that the proof of carbonate in apatite may allow no additional reference of an infection with urea-splitting bacteria. With certain analytical methods the presence of carbonate is demonstrable in each urinary calculus apatite phase. Carbonate-bearing apatite indeed is accompanied frequently with struvite, but may be occur also without an infection. Therefore, in the future it should be renounced on the differentiation of apatite and carbonate apatite in routine analyses of urinary calculi.

Apatites↗