Successful pregnancy after uterine artery embolization for uterine arterovenous malformation: a rare case report.

OBJECTIVE: This paper reports on a rare case of pregnancy after uterine artery embolization (UAE) for uterine arteriovenous malformation (AVM). Debate exists about persistence of fertility in women after UAE. Adverse effects of this technique can modify both uterine echostructure, inducing necrosis and infarction, endometrial atrophy and uterine artery rupture, and ovarian reserve, causing persistent amenorrhea. Ovarian reserve appears to be affected by UAE in pre-menopausal women. However, younger ovaries (according to biological ovarian age) exhibit a greater capacity for recovery after ovarian damage. Therefore, larger studies are needed for more conclusive results. CASE REPORT: A 28-year-old woman was admitted to our department due to life-threatening uterine bleeding, resulting in tachycardia, pallor, and sweating. The patient came with a history of two spontaneous miscarriages. After sonography and computed tomography, AVMs were identified at uterine fundus and anterior wall. CONCLUSION: The pathogenesis of infertility after UAE is not yet known. The peculiarity of this case was that, only few months later, the patient became pregnant and gave birth to a live fetus at 37 weeks with cesarean delivery.

The rise and fall of compartmental analysis.

The concept of compartment evolved in the contexts of radioactivity, physiology, pharmacology and tracer kinetics. Recently compartmental models have been compared with 'physiological models', even though in most cases the same, or stricter hypotheses, are necessary for the validity of these latter models. This paper shows that the methods of compartmental analysis are valid only if some specific hypotheses are valid.

Bioequivalent or nonbioequivalent?

The current tests for bioequivalence are based on assumptions that are not valid in general; this paper shows why it is necessary to use a method that does not depend upon assumptions that cannot, and need not, be proved in general.

Area under the curve and bioavailability.

The Area Under the Curve (AUC) is proportional to the fraction absorbed only if the clearance is constant and the concentration uniform; in all other cases the bioavailability cannot be determined by comparing AUCs.

Compartmental analysis revisited.

This paper gives a precise definition of compartment and shows that even when a compartmental model is not exactly identifiable, a range of its pharmacokinetic parameters can be determined. It is thus better to know approximate values of clearly defined parameters than exact values of quantities with no physical or physiological content.

On the determination of bioequivalence.

The characteristics and advantages of a new method for the determination of bioequivalence are described. This method does not employ AUC or Cmax, therefore it does not depend on a number of assumptions usually needed for the validity of the traditional method.

Some aspects of tyrosine secondary metabolism.

The origin and fate of some tyrosine secondary metabolites within specialized eukaryotic cells are discussed in the light of our knowledge of the plasma environment to which they are exposed throughout their lifetime. Attention is focused on ar-dihydroxy and -trihydroxy derivatives and the corresponding quinoidal counterparts, as well as on the enzymic activities involved in the formation and degradation of these potentially toxic molecules. Some physiopathological and pharmacological implications of the above-mentioned topics are considered, taking into account the well known toxicity of reactive intermediates in molecular oxygen reduction, as well as the reactivity of both semiquinonic and quinonic products of catecholamine oxidation.

Effect of 3-hydroxyanthranilic acid on mushroom tyrosinase activity.

Tyrosinase is a copper containing protein which catalyzes the hydroxylation of monophenols and the oxidation of diphenols to o-quinones. The monophenolase activity of tyrosinase is characterized by a typical lag time. In this paper the influence of 3-hydroxyanthranilic acid on monophenolase activity of tyrosinase is reported. 3-Hydroxyanthranilic acid reduced the lag time of tyrosinase when the enzyme acted on N-acetyl-L-tyrosine and on 4-tert-butylphenol. In the presence of 3-hydroxyanthranilic acid, the reaction product 4-tert-butyl-o-benzoquinone, derived from 4-tert-butylphenol oxidation, was formed at a higher rate than in its absence. The results reported in this paper indicate that 3-hydroxyanthranilic acid could affect the enzymic activity of mushroom tyrosinase probably by acting as a diphenol substrate. A K(m) value of 0.78 mM was calculated for 3-hydroxyanthranilic acid as substrate. When tyrosinase acted on 4-tert-butylphenol, K(m) for 3-hydroxyanthranilic acid as a cofactor was estimated to be 37.5 microM. No effect was observed on the diphenolase activity of the enzyme acting on 4-tert-butylcatechol in the presence of 3-hydroxyanthranilic acid.

Biosynthesis of the topaquinone cofactor in copper amine oxidases--evidence from model studies.

Copper amine oxidases utilize 2,4,5-trihydroxyphenylalanine quinone (topaquinone) as a cofactor in enzymatic catalysis. This cofactor is formed from a tyrosine residue through a self-catalytic mechanism with the participation of the copper ion at the active site. Although pathways have been postulated for topaquinone biogenesis, portions of this scheme are still unclear. We utilized 4-tert-butyl-derived models for the putative intermediates of topaquinone generation and studied the effect of Cu(II) and Zn(II) ions on each autoxidative step from dopa- to topaquinone-like compounds at physiological pH (7.4). Several polyvinyl-alcohol-based soluble resins bearing mono- and di-hydroxyphenolic moieties were also prepared, and their tendency to give hydroxyquinonic structures when incubated at alkaline pH values was investigated. Our results confirm (although indirectly) the formation of dopa and dopaquinone during topaquinone biosynthesis. Moreover, we collected evidence that, following the formation of dopa, the role of the active-site copper ion in topaquinone biogenesis would be limited to the catalysis of the two subsequent quinonization steps (i.e. from dopa to dopaquinone and from topa to topaquinone), thus disfavoring the possibility of a direct intervention of the metal ion in the hydroxylation of dopaquinone. In particular, Cu(II) was shown to influence deeply the autoxidation of 1,2,5-trihydroxy-4-tert-butylbenzene, used as model of topa, both increasing the reaction rate and changing its mechanism. The mechanistic implications of these findings for the biogenesis of topaquinone and its analogs at the active site of various amine oxidases are discussed.

Polyphenol oxidase activity staining in polyacrylamide electrophoresis gels.

An analytical method allowing the detection of polyphenol oxidase activity on polyacrylamide gel electrophoresis (PAGE) is described. The method is rapid, sensitive and specific and is based on a coupling reaction between 4-tert-butyl-o-benzoquinone and the aromatic amine, 4-amino-N,N-diethylaniline sulphate. Catecholase activity of polyphenol oxidase appears as blue stained bands on a colourless background.

Clearance, turnover time, and volume of distribution.

In mathematics a parameter is a fixed quantity that determines the behavior of a function. In the experimental sciences a parameter is an observable quantity that remains constant for every definable state of a system. In pharmacology it is important to distinguish among pharmacokinetic parameters, model parameters, and incidental parameters. A pharmacokinetic parameter is a quantity that defines a pharmacokinetic property of a biologic entity; conversely a model parameter defines the property of a chosen model, and an incidental parameter defines only the result of an experiment. The three most important pharmacokinetic parameters are clearance, turnover time, and volume of distribution. They are related by the expression. Clearance x Turnover time = Volume of distribution.

Properties of Thermus aquaticus beta-NADH oxidase immobilised on various supports.

beta-NADH oxidase purified from Thermus aquaticus was covalently immobilised on various solid supports. The preparations obtained were compared with the soluble enzyme for activity and kinetic properties. Activated glutaryl-PVA was found to be the best support. The immobilised enzyme was less stable at high temperatures than the soluble enzyme. No differences could be detected in the presence of organic solvents.

[A new infusion method for a prostacyclin analogue]. / Nuova tecnica di infusione di un analogo delle prostacicline.

BACKGROUND: Iloprost, a prostaglandin I2, is chemically stable and it has been successfully used by intravenous infusion in severe limb ischemia. Usually Iloprost is diluted in 0.9% sodium chloride solution and infused intravenously for six hours each day for 28 days in hospital. METHODS: In the present study after the first three days of infusion with a traditional pump in hospital, a home pump has been utilised for the infusion of Iloprost at home. This device allows the continue infusion of Iloprost at a flow rate of 2 ml/h for six days, then the pump is filled with a new solution. The home pump consists of a protective shell in polycarbonate (10 x 12 cm), 270 ml of volume, inside there is a balloon reservoir (3 membranes) which is filled with Iloprost. The structure of Iloprost does not change into the home pump as evidenced by HPLC studies and its continue infusion allows plasmatic high levels of its active isomers during the 28 days of therapy. In 30 patients, 25 men and 5 women (mean age 61 years) with Fontaine stage IIB (6), III (5) and IV (19) POAD Iloprost has been infused with the home pump. The follow-up period was 1 to 16 months. RESULTS: The results have shown 4 major amputations and 1 death, in 9 patients complete pain relief and ulcer healing, and in 6 patients only improvement in relief of rest pain and ulcers. CONCLUSIONS: All the patients appreciated this system of infusion because they had a normal life; in addition it is less expensive because the patients stay in hospital only 3 days.

Dopaquinone hydroxylation through topaquinone cofactor in copper amine oxidases: a simplified chemical model.

A simple model, 4-tert-butyl-1,2-benzoquinone, was chosen to study the hydroxylation step of the tyrosine-derived Dopaquinone residue at the active site of copper amine oxidases in the self-catalytic generation of the Topaquinone cofactor. This hydroxylation step was studied both in the presence and absence of free copper(II), and was found to be dependent on pH value but not on the presence of metal ions. It is therefore proposed that, hydroxide ion and not water should be the true reactive species in this key biosynthetic step of the Topaquinone cofactor, and that the active site Cu2+ is implied, at this point of cofactor biosynthesis, in the quinonisation of Topa rather than in the hydroxylation of Dopaquinone.

Mefenamic acid bioequivalence assessment with a new statistical procedure.

The bioequivalence of three different formulations of mefenamic acid was tested using the index zeta 2 previously defined by Rescigno. This index is a measure of the distance in Hilbert space of two concentration vs time functions; unlike the approach of Westlake which assumes a multiplicative model for the AUC and Cmax characteristics, this approach does not imply any hypotheses on the structure of the data and no particular model of the absorption or of the elimination processes. The index zeta 2 is simply an indication of how similar two formulations are. Results for this new test were compared with those obtained with two other tests, namely 90 and 95% symmetrical confidence intervals of Westlake and two one-sided t-tests of Shuirmann through the 90% confidence intervals in the ranges 80-125% for AUC and 70-143% for Cmax. Results of the new test are fully comparable with those obtained using the other two tests.