Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Design of an intravenous oxygenator

The aim of this study was to design a new intravenous blood–gas exchange device and to estimate the design characteristics of the device with a dimensionless function by using a substance that can be used instead of bovine blood. In addition, the characteristics of oxygen transfer were estimated using empirical formulas and the reliability of the equations was ascertained by comparing their output with an experiment performed using bovine blood. The dimensionless function was derived using distilled water and bovine blood to estimate the oxygen transfer rate. Using the derived equations, the calculated oxygen transfer rates for bovine blood and distilled water were similar for Reynolds numbers ranging from 0.7 to 7.0. Therefore, it is possible to estimate the oxygen transfer rate in bovine blood, which is a non-Newtonian fluid, using distilled water, which is a Newtonian fluid. Moreover, it was possible to verify the related equations because the oxygen transfer rate could be estimated using the derived equations, according to the diameters of the various device modules.     

Identifying Risk Drinking in Expectant Fathers

Abstract: Background: Identification of risk drinking in expectant fathers may be helpful as an important part of efforts to minimize maternal alcohol use, and as an opportunity to inform them about a problematic practice during a critical developmental stage for the couple. The purpose of this study was to evaluate the T‐ACE screening questionnaire, which asks about t olerance to alcohol, being a nnoyed by other's comments about drinking, attempts to c ut down, and having a drink first thing in the morning (“ e ye‐opener”), in the male partners of pregnant women who themselves were T‐ACE positive. Methods: Two hundred fifty‐four male partners were asked to complete the T‐ACE embedded in a health survey, the Alcohol Use Disorders Identification Test (AUDIT), and other questions about their alcohol use in the past 30 days when their pregnant partners had a median gestation of 11.5 weeks (T₁). After delivery, male partners again completed the T‐ACE and quantity‐frequency questions (T₂). The predictive ability of the T‐ACE and AUDIT was compared, using risk drinking (>4 drinks/day or >14 drinks/week) as the criterion standard. Results: A substantial minority of male partners had risk drinking, 31 percent at T₁ and 25 percent at T₂. Although the AUDIT was better than the T‐ACE as an independent predictor of risk drinking, the latter was most accurate when the tolerance threshold exceeded 2 drinks, the same established for pregnant women. The sensitivity (T₁ = 84.6%, T₂ = 82.8%) and specificity (T₁ = 43.8%, T₂ = 51.1%) of the T‐ACE at this threshold compared favorably with those of the AUDIT at the standard cut point of 8. Conclusions: The T‐ACE may be a practical way for clinicians to identify risk drinking in both pregnant women and expectant fathers. (BIRTH 33:2 June 2006)     

Dry skin in dermatology: a complex physiopathology

Dry skin (xerosis) is a common dermatosis affecting people of varying skin types and ages and various areas of the body. It is associated with both skin thickening and skin thinning and is triggered by both exogenous (e.g. climate, environment, lifestyle) and endogenous (e.g. medication, hormone fluctuations, organ diseases) factors. Skin requires a water content of 10–15% to remain supple and intact. This water is either ‘static’ (i.e. bound) or ‘dynamic’. The predominance of hydrophobic substances in intercellular constituents is a means of regulating the humidity of the skin. Emollients, highly effective treatment adjuncts in the management of all dry skin disorders, help to restore damaged intercorneocyte lipid structures and increase the water content of the skin, helping to reduce scaling and improving its barrier function.     

Detection of glaucomatous damage using multifocal ERG

The first‐order kernel analysis in multifocal electroretinogram (mfERG) using low contrast stimulation is suggested as a way to detect the inner retinal responses in animal studies. In this case report, this protocol is applied to human patients with glaucoma to demonstrate the possibility of using mfERG as a tool to detect glaucomatous damage. Two patients with glaucoma were recruited and had mfERG measurements with the 103‐scaled hexagonal stimulus pattern at low (50 per cent) contrast. Their responses were analysed and compared with those from normal subjects with the mfERG measured under the same condition. In the normal subjects, there were obvious oscillatory components on the ascending and descending limbs of the first‐order kernel response to 50 per cent contrast. In the glaucomatous patients, the oscillatory component on the descending limb was obviously diminished. In addition, this component was significantly diminished in the quadrant with a glaucomatous visual field defect. This suggests that the low‐contrast stimulation condition in mERG measurement may provide a good way to detect glaucomatous damage and this may help in clinical diagnosis of glaucoma.     

Anterior mediastinal immature teratoma with precocious puberty in a child with Klinefelter syndrome.

ABSTRACT: Klinefelter syndrome occurs in approximately 1 in 1000 males. A 4-year-old boy presented with precocious puberty and an anterior mediastinal mass. Serum alpha-fetoprotein and human chorionic gonadotropin levels were mildly increased. Computed tomography revealed a germ cell tumor (GCT) of the mediastinum. Complete resection of the tumor was performed. Histologic analysis revealed an immature teratoma. Males with Klinefelter syndrome develop GCTs at a rate 50 times higher than unaffected males. This case report calls attention to the need to rule out Klinefelter syndrome in boys who present with precocious puberty and a mediastinal GCT.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.