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Biomedical subjects

J Florian

Publications and source records attributed to J Florian.

14 recordsLinked to original sources
PubMed1999

Mechanistic alternatives in phosphate monoester hydrolysis: what conclusions can be drawn from available experimental data?

Phosphate monoester hydrolysis reactions in enzymes and solution are often discussed in terms of whether the reaction pathway is associative or dissociative. Although experimental results for solution reactions have usually been considered as evidence for the second alternative, a closer thermodynamic analysis of observed linear free energy relationships shows that experimental information is consistent with the associative, concerted and dissociative alternatives.

Animals↗
PubMed1996

Ab initio investigation of the molecular structure of methyl methoxymethyl phosphonate, a promising nuclease-resistant alternative of the phosphodiester linkage.

Conformational flexibility of the methyl methoxymethyl phosphonate anion (CH3-O-PO2-CH2-O-CH3)-, a nuclease resistant alternative to the phosphodiester linkage in DNA, have been investigated by ab initio quantum mechanical calculations. The potential of backbone torsional degrees of freedom of methyl methoxymethyl phosphonate anion (MMP) was determined at the Hartree-Fock (HF) 3-21G* level using the adiabatic mapping technique. Energies, geometries, and effective atomic charges of different conformers were calculated at HF/6-31G* and MP2/6-31G* levels of theory. These were compared to the results obtained for dimethyl phosphate calculated at the same level. The impact on DNA structure from inserting a methylene group between phosphorus and oxygen of the nucleoside sugar moiety was examined via distance and angle-constrained geometry optimizations. Due to its high flexibility, MMP has been shown to be compatible with both A and B forms of DNA.

Deoxyribonucleases↗
PubMed1996

[Stimulants].

The authors present a comprehensive account of stimulants from chemical structure to clinical use. They analyze in detail the function and pharmacokinetic properties of stimulants but also their clinical and undesirable side-effects. The section on the interaction of stimulants and other drugs and other types of treatment is very important. The second part of the paper deals with indications and contraindications of stimulants, incl. the possible risk of the development of dependence. There are many indications for stimulants in clinical (in particular paedopsychiatric) practice.

Central Nervous System Stimulants↗
PubMed1996

[Attention deficit in hyperactive children].

The most typical features of hyperactivity in children (ADHD) are deficient attention, impulsiveness and hyperactivity on which the present paper is focused. With this problem symptoms are associated such as sensomotor problems, intellectual questions, impaired sleep, emotional disorders and behavioural disorders. The part devoted to etiology analyzes the impact of the environment and of genetic factors on ADHD whereby the latter factor is dominant. As regards treatment, the authors discuss not only pharmacological treatment, but also counselling for parents and teachers of thus affected children.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

[Effect of Aponeuron in the treatment of children with hyperkinetic syndrome].

The submitted original paper deals with hyperactivity of children (ADHD) and their treatment by means of the stimulant Aponeuron. The authors made a long-term, double blind, placebo controlled trial which comprised more than 20 hyperactive children. The applied methods are described in detail and the results of individual investigations are summarized. Moreover it is a subject to which in the local professional literature, contrary to that in other countries, little attention was paid, although it is a frequent disorder. Administration of Aponeuron (and stimulations in general) proved useful in the treatment of this disorder. The subtle and crude motorics improved, symptoms of hyperactivity disappeared and the general school performance of the child improved.

Amphetamines↗
PubMed1994

The isolated perfused kidney of the pig: new model to evaluate shock wave-induced lesions.

Little is known about the mechanisms and determining factors of shock wave-induced kidney trauma. After classification of the renal lesion in a canine model, we attempted to establish an ex vivo model using the isolated kidney of the pig perfused by Tyrode's solution under physiologic conditions. After shock wave application on the Modulith SL 20, vessel lesions were evaluated by microangiography to determine the size and frequency of dye extravasation in the different areas of the organ. Variation of the focus localization caused different patterns of lesions that characterized the pathway of the shock wave. In particular, constant petechial extravasation in the cortex was observed. The generator voltage correlated with the diameter and the frequency of the lesion area. The number of shock waves primarily affected the incidence of vessel rupture in the regions adjacent to the focal zone. Light microscopy revealed dose-dependent necrosis of tubular cells up to gap-like parenchymal defects. Even after application of the minimal shock wave doses, electron microscopy demonstrated vacuolization of tubular cells in the shock wave focus. Traumatic junctions between capillaries and the tubulur system can explain clinically observed macrohematuria without renal hematomas. With this model, it was possible to evaluate localization and dose dependence of shock wave-induced kidney trauma with high sensitivity and reproducibility. Further advantages of the model were easy availability and the fact that studies on living animals were not necessary. Therefore, standardization and comparison of different lithotripters becomes possible.

Angiography↗
PubMedDate not supplied

Phase II trial of oral tegafur and folinic acid with mitoxantrone as first-line regimen in patients with metastatic breast cancer.

BACKGROUND: Tegafur acts as a deport form of 5-fluorouracil when administered orally for long periods of time since it is an active drug in metastatic breast cancer, with response rates of 29-44%. Biochemical modulation with folinic acid and the addition of mitoxantrone could increase the efficacy of tegafur in patients with metastatic breast cancer. METHODS: A prospective phase II trial in patients with previously untreated metastatic breast cancer was carried out. The scheme consisted of mitoxantrone, 12 mg/m2 intravenous day 1, oral tegafur, 750 mg/m2/day divided in three equal doses, and leucovorin 15 mg/8 h orally for days 1-21, given in a 4-week schedule. None patient had received chemotherapy for metastatic breast cancer, although 16 patients had received previous adjuvant chemotherapy. RESULTS: Thirty-four patients were included. Objective responses were achieved in 20 of 32 patients assessable for response, with 1 complete response and 19 partial responses. The objective response rate was 62.5% (95% confidence intervals, 48-76%). The median duration of response was 10 months. Grade III-IV toxicity according to WHO criteria was digestive (nausea/vomiting) in 12.5%, diarrhea in 25% and stomatitis in 25% of patients. Other toxicities were low. Eight patients required dose-reduction. CONCLUSIONS: We achieved a significant response rate with the scheme, which was administered on an outpatient basis. It seems to be safe and effective as first-line treatment in metastatic breast cancer, with a short median response duration. The size of the trial does not permit definitive conclusions, and the role of biochemical modulation of tegafur in combination with mitoxantrone remains to be defined.

Administration, Oral↗