Pharmacokinetic and bioequivalence study of two gemfibrozil preparations

A comparative pharmacokinetic study has been performed in 19 healthy male volunteers in a single-dose, randomized, two way cross-over design with two preparations of gemfibrozil (CAS 25812-30-0) capsules each of them containing 300 mg active ingredient. The test preparation was Innogem 300 mg capsule. The plasma concentration of gemfibrozil was determined by a validated HPLC-UV analytical method. The statistical comparison of individual pharmacokinetic parameters (AUC0-16, AUC0-oc Cmax, tmax) of the two capsule preparations was performed by three-way analysis of variance (ANOVA), Wilcoxon's, Westlake's, Schuirmann's and Hanck-Anderson's method as well as by the calculation of confidence intervals on the ratio of test/reference. The relative bioavailability of the test preparation with respect to the reference preparation in terms of the AUC0-oc was 104.06 +/- 21.61%. No statistically significant difference was found between the pharmacokinetic parameters, calculated from plasma concentration-time curves, indicating that the two preparations were bioequivalent.     

Perineal endometriosis at the site of an episiotomy scar

This study presents a case of vaginoperineal histologically verified endometriosis at the site of episiotomy scar in a 40-year female subject, 17 years after delivery. Apart from episiotomy during delivery manual revision of the uterus was performed and the cervical rupture managed. Residue symptoms occurs 8 months after the first surgical excision. Clinical data indicate that decidua implantation at the site of episiotomy occurred during the manual revision of the uterine cavity during delivery.     

A PMLRARalpha transgene initiates murine acute promyelocytic leukemia

The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha). To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice. PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.     

Simplified modeling of transients in gain-clamped erbium-dopedfiber amplifiers

A simple technique for modeling transients in erbium-doped fiber amplifiers (EDFAs) has been applied to a gain-clamped amplifier. Integration of the variables along the length of the amplifier allows the formulation of the problem as a single simple, ordinary, time-dependent differential equation. We demonstrate examples for a typical conventional EDFA and one in which internal out-of-band oscillation is used to clamp the gain     

Auswirkungen von Blitzschlägen auf 20-kV-Energiekabel

Recently appeared defects on high voltage cables have required an urgent evaluation of the impact of lightning strikes necessary. In some cases overvoltages between the copper wire screen of the cable and earth may appear which cause damages of the cablesheath. Field measurements with a classification of the voltage impulses at the copper wire screen have been made to evaluate the number of events. Additionally a numerical model was developed to study the effects of atmospheric discharges on underground cables with emphasis to the influence on the cablesheath. This numeric method was also applied to estimate the effectiveness of different protection arrangements. This contribution presents evaluation methods for overvoltages of cables and a model used firstly for calculating the stress caused by differential voltages and secondly to determinate the influence of protection measures.     

Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.     

Laboratory studies in cross-species lung transplantation

The lack of sufficient suitable human donor lungs for the many patients requiring pulmonary transplantation as life-saving therapy for end-stage lung diseases has generated extensive interest in cross-species lung transplantation. Ethical concerns and those of animal rights advocates have prompted studies of nonprimate species as potential solid organ donors for humans. This paper provides an overview of some of the laboratory studies of cross-species pulmonary transplantation performed over the past 20 years and focuses, in particular, on more recent work (from our laboratory and others) in the area of porcine-to-primate pulmonary xenotransplantation.     

In vivo assessment of human skeletal muscle mitochondria respiration in health and disease

One of many problems to be faced when assessing in vivo human muscle mitochondria respiration by phosphorus magnetic resonance spectroscopy (31P-MRS) is the definition of the correct reference population and the values of reference range. To take into account most factors that influence muscle activity as age, sex, physical activity; nutritional state etc., an exceedingly high number of different reference groups are needed. To overcome this problem we developed specific tests to assess separately in vivo the activity and the functionality of muscle mitochondria by 31P-MRS in clinical settings. By activity we refer to muscle whole metabolic activity, i.e. the total oxidative capacity of muscle mitochondria which is influenced by many factors (age, sex, physical activity, nutritional state etc.). By functionality we refer to the qualitative aspects of mitochondrial respiration which depends on the integrity of mitochondrial multienzyme systems and on substrate availability. Our tests have been experienced on some 1200 patients and are currently used to detect deficits of mitochondrial respiration and ion transport in patients with suspected primary or secondary muscle mitochondrial malfunctioning.     

Possibilities and limits of extracranial vascular diagnosis with conventional echography

OBJECTIVE: To evaluate the efficacy of terazosin, an alpha-blocker, for the treatment of idiopathic oligozoospermia. PATIENTS AND METHODS: Thirty couples with infertility whose only detectable abnormality was male idiopathic subfertility entered the study. The diagnosis of idiopathic subfertility in all males studied, aged 26 to 38 years (mean 28.2 years), was confirmed after exclusion of any iatrogenic, systemic, congenital, infectious, autoimmune or endocrinological cause. In order to start with a baseline value before the study, at least three semen samples were evaluated in accordance with the WHO recommendation. Before initiation of treatment, blood samples were drawn for measurement of FSH, LH, testosterone, prolactin, dihydrotestosterone, and estradiol. Fifteen randomly selected patients (Group A) received 2 mg/d of alpha-blocker (terazosin), while another 15 (Group B) were administered an identically packed placebo tablet. Both groups received therapy for 6 months. RESULTS: The mean seminal volume changed insignificantly between the two groups (4.15 +/- 1.95 vs. 4.10 +/- 1.95). There was a statistically significant increase of the sperm concentration in patients who received the alpha-blocker compared to those receiving placebo (24.76 +/- 9.45 vs. 13.15 +/- 11.55 millions/mL; P < .001). No improvement of the mean percentage of abnormal spermatozoa was observed in the treated patients, nor a statistically significant difference of sperm motility in the treated group compared to the placebo group. Side effects were not observed in the patients receiving terazosin treatment, or were so minimal that therapy was continued. The pregnancy rates did not differ between the two groups to a statistically significant degree. CONCLUSION: The administration of terazosin to patients with idiopathic oligozoospermia has a demonstrably positive effect, especially on sperm concentration.