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Biomedical subjects

Z Fendrich

Publications and source records attributed to Z Fendrich.

At least 19 recordsLinked to original sources
PubMed2002

[Physiologic function of P-glycoprotein].

P-glykoprotein has been proposed to function as a membrane transport protein for a large variety of substrates, ranging from small lipophilic molecules, steroid hormones, lipophilic peptides, some drugs, biologically important molecules and xenobiotics. There is little doubt that P-glycoprotein transports a wide range of substrates out of cells, nevertheless it is difficult to explain its wide substrate specificity and mechanism of the transport. P-glycoprotein has been found to be a major cause of acquired multidrug resistance (MDR) of cancer cells to chemotherapeutic drugs. The identification and localization of P-glycoprotein expression in a variety of normal human tissues raised the question of the physiological functions of P-glykoprotein. Currently, there is considerable evidence that P-glycoprotein can protect the body and sensitive tissues against a range of different xenobiotics. In addition, P-glycoprotein might play a role in regulation of cell differentiation, proliferation, immune response and programmed cell death.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Influence of P-glycoprotein on the transplacental passage of cyclosporine.

The transfer kinetics of cyclosporine across the dually perfused rat placenta in the maternal to fetal direction and a possible involvement of P-glycoprotein were investigated. The transplacental clearance of cyclosporine in the materno-fetal direction was found to be dependent on the maternal inflow concentration of cyclosporine. Coadministration of cyclosporine with an excess of quinidine or chlorpromazine into the maternal compartment revealed 1.7- and 1.9-fold increase in cyclosporine concentration in the fetal compartment. In the experiments where quinidine was present both in the maternal and fetal compartments, cyclosporine appeared in the fetal compartment significantly faster, and its amount was three times higher when compared with controls. Conversely, quinidine or chlorpromazine did not affect the transplacental passage of L-[(3)H]-glucose. The interference of quinidine with the metabolism of cyclosporine in the placenta was excluded because only traces of M-1 and M-17 metabolites were found in the fetal solutions. Sodium azide, a mitochondrial respiratory inhibitor, was found to double the rate of cyclosporine, but not L-[(3)H]-glucose, passage across the placenta. Our findings indicate that P-glycoprotein pumps cyclosporine out of the trophoblast cells of the rat placenta in the ATP-dependent manner and restricts the passage of cyclosporine across the placental barrier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Metamizol--a new effective analgesic with a long history. Overview of its pharmacology and clinical use].

Metamizol is an effective, non-opioid analgesics which was originally introduced to the therapy in the year 1922. However, with the reference to the side effects of other related pyrazolone derivatives its administration, similarly as the usage of other pyrazolones, was significantly limited. Later, metamizol has been used, usually mixed, with spasmolytic agents and quite recently it has been introduced as a mono-component medicament. Metamizol proved to be a very effective analgesic. When administered in equipotent doses, it had its effects comparable to various opioid analgesics, such as tramadol, pentazocine and pethidine. Beside the strong analgesic effect, it produces also significant antipyretic and splasmolytic effects without the adverse, unpleasant anticholinergic impact. Its spasmolytic effect on the smooth muscle of the sphincter Oddi, urinary tract, and the gal bladder is comparable to the effects of buthylscopolamine. Unlike aspirin and other nonsteroidal antiinflammatory drugs it has, however, no antiinflammatory activity when administered in clinical doses. Similarly, metamizol has no effect on the CNS, cardiovascular system, renal and metabolic functions. On the other hand, metamizol, like aspirin, has got a significant effect on the aggregation of platelets. Metamizol is basically a prodrug. The parent substance is not effective before its conversion into two active metabolites (4-methylaninoantipyrine and 4-aminoantipyrine) in the body. Metamizol is well absorbed from the small intestine but only two above mentioned active metabolites and no parent drug can be detected in the blood. The active metabolites are consequently metabolised to ineffective metabolites including the relevant acetylderivatives, in which the acetylation phenotypes can be distinguished. In the therapy, metamizol can be used, as an analgesic, at post-surgical pain, patient's controlled analgesia (PCA), at the cancer's pain and in the pains of different origin (post-traumatic pain, the pain at myocardial infarction, craniocerebral trauma, and the invasive diagnostic interventions), as well as at he pain of neuromuscular origin, headache and migraine. Its spasmolytic effect in connection with a strong analgesic activity is very useful at various colic attacks. Further, metamizol is a useful antipyretic both in the adults and children. Its adverse effects are not pronounced and drug interactions are minimal. Only when metamizol is administered together with cyclosporine, the blood levels of the last substance should be regularly checked.

Analgesics↗
PubMed2000

[Effective and safe pharmacotherapy of acne vulgaris and treatment of sun-damaged skin].

An inevitable condition for the pharmacist is a basic knowledge of dermatological changes which are prominent in acne and solar impairment of the skin to be able to recommend in a qualified manner an effective and safe treatment to the patient. However, sufferers of the more serious forms of acne should always be referred to their general practitioner, or preferentially a dermatologist. Acne vulgaris is an androgen-induced disorder, but three major mechanisms for the development of the disease have been identified: hypertrophy of the sebaceous gland, hyperkatosis of the follicular epithelium, and proliferation of microbial flora, particularly Propionibacterium acnes. The basis of all lesions is the microcomedone which is developed into the ripe comedone. Inflammatory lesions are thought to be due to proliferation of P. acnes. In the selfmedication of common acne, benzoyl peroxide, which in a 5-10% lotion exerts antimicrobial and keratolytic properties, proved to be useful. Patients appreciate a lot its instant effect which is visible after just one day of treatment. Salicylic acid is another effective drug, which, when used on the long-term basis, has comedolytic properties; it reduces the number of microcomedones and counteracts plugging of the follicles. In addition, in healthy young women who take oral contraception, a triphasic combined oral preparations of contraceptives with newer progestins, notably with norgestimmate, which is practically free of androgenic effects, are recommended with advantage for the treatment of moderate acne vulgaris without any adverse effects. Solar impairment of the skin, the so-called solar ageing, is clinically indistinguishable from biological ageing. Changes connected with solar impairment appear mostly in the dermis, where solar elastosis develops, the skin gets drier and wrinkle formation appears. For the treatment, hydroxy acids are recommended, namely salicylic acid, which is very effective, because in combination with a suitable vehicle it produces desquamation or exfoliation. Desquamation is beneficial as it gives a youthful appearance to the skin.

Acne Vulgaris↗
PubMed1999

[Common gastrointestinal symptoms and their effective and safe treatment].

The pharmacist is an important specialist in the selection of the drug when the patient comes for pharmacist's advice of how to alleviate common gastrointestinal symptoms. Of all drugs which can be effective in these situations, only three drugs (bismuth subsalicylate, psyllium, and docusate sodium) proved to be advantageous for self-medication. Bismuth subsalicylate (BSS) is much appreciated in the treatment of peptic ulcers where it not only covers the base of the ulcer but also eradicates Helicobacter pylori. Therefore this drug does not treat only the symptoms but the cause of the disease as well. Dyspepsia may also be effectively treated with BSS because of its strong and rapid protective effect on the gastric mucosa. Last but not least, the salicylate component of this substance and not bismuth alone is responsible for the elimination of diarrhoea in the so-called traveller's diarrhoea, as the salicylate decreases enhanced secretion of fluid in the colon. On the other hand, the natural fibre psyllium may effectively alleviate constipation, because it increases the volume and weight of stools as well as the transit time in the colon and facilitates defecation. Similarly, docusate sodium is a detergent agent which facilitates the entrance of water into the stool, which is then better and more easily pushed out from the large intestine.

Bismuth↗
PubMed1998

Unidirectional transfer of D-xylose across the rat placenta.

1. The transplacental transfer of D-xylose was investigated in the present study. 2. Umbilical perfusion of the rat term placenta was used to study materno-foetal (M-F) and foetomaternal (F-M) transfer of this compound. 3. D-Xylose was found to cross the rat term placenta very quickly in the M-F direction, with subsequent accumulation in the foetal compartment (the F-M ratio being 2.23 at the end of the experiments). In contrast, no transfer in the F-M direction was observed. 4. A possible facilitation of the transplacental transfer of D-xylose from the mother to foetus in rats is suggested.

Animals↗
PubMed1998

Different transfers of N-acetyl-p-aminobenzoic acid and p-aminobenzoic acid across the placenta and the small intestine in rats.

The aim of the present study was to evaluate the transfer of N-acetyl-p-aminobenzoic acid (AcPABA) across the rat term placenta and the rat small intestine and to compare it with that of its parent drug p-aminobenzoic acid (PABA). Umbilical perfusion of the rat term placenta was used to determine the materno-fetal transfer. AcPABA appeared in the fetal compartment significantly more slowly than PABA (k transfer = 0.023 and 0.064 min(-1), respectively). The rate of equilibration between the maternal and fetal compartments was slightly lower for AcPABA than for the parent drug (k eqilibration = 0.0082 and 0.011 min(-1), respectively). Similarly, AcPABA was shown to be absorbed from the small intestine significantly more slowly than PABA (ka = 0.052 and 0.82 min(-); tmax = 37 and 3.1 min, respectively). Our results showed that both investigated compounds which are structurally related and very similar in their physical-chemical characteristics crossed both the placental and small intestinal barrier with a different kinetics. AcPABA was transported across both barriers significantly more slowly than its parent compound, which might indicate a possible equipment of the placenta with a carrier for PABA, a similar one to that previously found in the rat small intestine.

4-Aminobenzoic Acid↗
PubMed1998

[Self-medication of the common cold].

Self-medication can be useful in the multisymptomatic management of the common cold and other preferentially non-febrile flu-like symptoms, especially as at present multicomponent remedies are available, which may make self-medication significantly easier with consequent better compliance of adult patients. Children, on the contrary, are not suitable acceptants of self-medication mediated by their parents because the sickness exhibits in children nearly exclusively febrile progress. The procedure of the therapy to be really effective and safe must be necessarily concentrated into pharmacies, where safety and efficacy of therapy are ensured by the pharmacist as the last link of contact between the patient and the drug. Any other distribution of the OTC drugs is therefore strictly unacceptable. Patients suffering from the common cold usually exhibit simultaneously various symptoms of the disease. These different symptoms are, however, experienced during the day with different intensity. During the day and often also in the course of the labour process there is a need to concentrate on the most bothersome symptoms, notably the relief of the nasal congestion with the exploration of the safest and most effective drug, such as pseudoephedrine. In addition, it is necessary to administer an effective nonsteroidal anti-inflammatory drug, preferably ibuprofen, which provides relief from symptoms caused by release of inflammatory mediators. In the night time there is a need of a multisymptom therapy which may relieve cough and any other disturbing cold symptoms to allow satisfactory beneficial, continuous, and refreshing sleep.

Adult↗
PubMed1997

Pharmacokinetic examination of p-aminobenzoic acid passage through the placenta and the small intestine in rats.

In the present study the permeability of the rat small intestine and the placenta to p-aminobenzoic acid (PABA) and antipyrine (AP) was investigated. Perfusion of the rat term placenta was used to determine the materno-fetal transfer of both compounds. PABA appeared in the fetal compartment faster than AP (ktransfer = 0.064 and 0.046 min-1, respectively). The rate of equilibration between the maternal and fetal compartments and placental clearance were lower for PABA than for AP (kequilibration = 0.011 and 0.020 min-1; Clp = 0.22 and 0.33 ml/min, respectively); the feto-maternal concentration ratios at equilibrium (FMCReq) were, however, mutually comparable. Similarly, PABA proved to be absorbed from the small intestine significantly faster than AP (ka = 0.824 min-1 and 0.479 min-1; tmax = 3.1 min and 8.9 min, respectively). The apparent volume of distribution (Vd) of AP in non-pregnant animals showed that the drug is distributed into the whole body water as expected (Vd = 0.66 l/kg); however, Vd of AP in pregnant animals was estimated to be 1.81 l/kg. Vd of PABA in non-pregnant animals showed its partially limited distribution, which was only slightly increased in the pregnant animals. Our results confirmed a faster penetration of hydrophilic PABA across the placenta and the small intestine than that of lipophilic AP. The mechanism of transplacental passage of PABA, however, remains to be determined.

4-Aminobenzoic Acid↗
PubMed1997

Phenytoin transfer across the in situ perfused rat term placenta.

Transfer of phenytoin (PHT) across the rat term placenta perfused in situ was investigated and compared with that of antipyrine (AP) as a marker of passive diffusion. PHT was shown to cross the placenta with similar kinetics as AP did. Both the first order transfer constant (ktr = 0.070 min-1) and the first order equilibration constant (keq = 0.027 min-1) of PHT were comparable to those of AP (ktr = 0.046 min-1, keq = 0.022 min-1). Similarly, there were significant differences between PHT and AP in the foeto-maternal concentration ratio at equilibrium (FMCReq = 1.01 and 1.09, respectively). The present data indicate that the transfer of PHT through the rat placenta is governed by the same principles as that of AP, i.e. by the mechanism of passive diffusion. Surprisingly, maternal plasma protein binding of PHT (60.5%) did not seem to influence either its rate of transfer or its eventual foeto-maternal concentration ratio.

Analgesics↗
PubMed1996

Mechanisms of action of some air pollutants on the airways.

Common air pollutants (O3, SO2) exert their deleterious effects in several ways, mostly on the respiratory functions. Ozone causes formation of peroxides and aldehydes with subsequent release of inflammatory lipids and cytokines. Changes in the activity of neutral endopeptidase and release of neuropeptides may occur. As a result, bronchial hyperreactivity can be detected. In the mechanisms of the disturbances due to sulfur dioxide, cholinergic mechanisms and release of neuropeptides may be involved.

Air Pollutants↗
PubMed1995

Analysis of pharmacotherapy of hypertension in out-patients.

In the present pilot study an attempt was made to evaluate the usefulness of results obtained about the treatment of patients suffering from high blood pressure for a pharmacoepidemiological study of the therapeutic value of antihypertensive agents. Data from 90 hypertensive patients were used in the present retrospective-prospective study. These patients all attended an out-patient clinic located in one of the East-Bohemian districts that are participating in the MONICA programme. Instead of the analysis of the population data, regular blood pressure measurements, plasma glucose levels, and total cholesterol concentrations were measured and analysed. The consumption of various antihypertensive drugs in this study was similar to that found in larger studies performed in other health districts of the Czech Republic. Diuretics were the drugs most frequently prescribed for hypertensive patients. General practitioners rarely prescribed calcium channel blockers and angiotensin-converting enzyme inhibitors in 1990 and 1991. The metabolic effects of antihypertensive drugs, mostly diuretics, were not significantly evident. The most frequent occurrence of non-compensated blood pressure was recorded for the treatments with Trimecryton and methyldopa. However, the validity of these findings should be tested in a larger group of hypertensic patients.

Adrenergic beta-Antagonists↗
PubMed1995

Pharmacokinetic parameters of verapamil and its active metabolite norverapamil in patients with hepatopathy.

Verapamil (CAS 52-53-9) is a calcium channel blocker with a vasodilatatory effect. Because of its significant first-pass effect, verapamil might be advantageous in the treatment of portal hypertension. It does not produce any excessive systemic effects, provided the doses are suitably adjusted. A decision was made to examine the pharmacokinetic parameters, independent of compartmental analysis of verapamil and its active metabolite norverapamil, in patients with portal hypertension. Their biological half-lives of the terminal phase were significantly prolonged as compared with the control group. However, no statistically significant differences were found in the values of tmax and Cmax. The calculated pharmacokinetic parameters of norverapamil were not significantly different from those of verapamil, except for the tmax of norverapamil, which was significantly longer in patients suffering from portal hypertension as compared with verapamil. The ratio of areas under the plasma concentration-time curve (AUC) of verapamil and norverapamil was comparable in both groups of patients. No relationship between the changes in the pharmacokinetic parameters and the extent of hepatic insufficiency was observed.

Adult↗
PubMed1981

Intestinal absorption of tolfenamic acid at experimental malabsorption states in rats.

Absorption kinetics of 14C-labelled N-(3-chloro-o-tolyl)-anthranilic acid (tolfenamic acid, 14C-TA, Clotam) from the small intestine was studied in intact rats and in rats with malabsorption states provoked by methotrexate, starvation, and triparanol. 14C-TA was administered intravenously and intraduodenally, and the drug concentrations in the blood were followed up radiometrically. A multi-compartmental model was applied for mathematical analysis. Theoretical model parameters were computed, and absorption parameters were then derived from the theoretical ones. The absorption half-life of 14C-TA was 5.3 min in the controls, 10.8 min in the methotrexate-intoxicated, 7.5 min in the fasted, and 5.3 min in the triparanol-intoxicated rats. The absorbed fraction of the intraduodenal 14C-TA dose was 100% in each experimental group as well as in the controls. It is suggested that the slower transfer of 14C-TA through the intestinal barrier in the methotrexate-intoxicated and fasted rats may be caused by the reduction of the absorptive surface.

Animals↗