Permeation of cytotoxic formulations through swatches from selected medical gloves.

The permeability of selected medical glove materials to various cytotoxic agents is described. Fifteen cytotoxic agents were prepared at the highest concentrations normally encountered by hospital personnel. Four single-layer and two double-layer glove systems made of two materials--latex and neoprene--were exposed to the drugs for 30, 60, 90, 120, 150, and 180 minutes. Circular sections of the glove material were cut from the cuff and evaluated without any pretreatment. Permeability tests were conducted in an apparatus consisting of a donor chamber containing the cytotoxic solution and a collection chamber filled with water (the acceptor medium). The two sections were separated by the glove material. Permeating portions, collected in water as the acceptor medium, were analyzed by either ultraviolet-visible light spectrophotometry or high-performance liquid chromatography (HPLC). Permeation rates were calculated on the basis of the concentration of the cytotoxic agent in the acceptor medium. Spectrophotometric measurements were taken every 30 minutes, and HPLC analysis was performed at the end of the three-hour period. Average permeation rates for 14 drugs were low (< 0.2 nmol/[min.cm2]) or no permeation was detected in all glove materials. All glove materials tested were impermeable to most of the cytotoxic agents over a period of three hours. Carmustine was the only agent that substantially permeated single-layer latex glove materials. Permeation of most tested cytotoxic formulations was low through swatches of material from various medical gloves.     

Gender in medical ethics: Re-examining the conceptual basis of empirical research

Conducting empirical research on gender in medical ethics is a challenge from a theoretical as well as a practical point of view. It still has to be clarified how gender aspects can be integrated without sustaining gender stereotypes. The developmental psychologist Carol Gilligan was among the first to question ethics from a gendered point of view. The notion of care introduced by her challenged conventional developmental psychology as well as moral philosophy. Gilligan was criticised, however, because her concept of two different voices may reinforce gender stereotypes. Moreover, although Gilligan stressed relatedness, this is not reflected in her own empirical approach, which still focuses on individual moral reflection. Concepts from social psychology can help overcome both problems. Social categories like gender shape moral identity and moral decisions. If morality is understood as being lived through actions of persons in social relationships, gender becomes a helpful category of moral analysis. Our findings will provide a conceptual basis for the question how empirical research in medical ethics can successfully embrace a gendered perspective.This revised version was published online in October 2005 with corrections to the Cover Date.     

In vitro screening for antitumour activity of Clinopodium vulgare L. (Lamiaceae) extracts

Aqueous extract of Clinopodium vulgare L. showed strong antitumour activity when tested in vitro on A2058 (human metastatic melanoma), HEp-2 (epidermoid carcinoma, larynx, human) and L5178Y (mouse lymphoma) cell lines-6 h after treatment disintegration of the nuclei and cell lysis started. Applied at a concentration of 80 microg/ml it reduced the cell survival to 1.0, 5.6 and 6.6%, respectively. The concentrations of aqueous extract inhibiting the growth of A2058, HEp-2 and L5178Y cells by 50% (IC50 values) were calculated to be 20, 10 and 17.8 microg/ml respectively. Two groups of active substances were detected: the first one, probably combining glycosides, influenced adhesion, while the second one caused massive cell vacuolisation. The chloroform extract, which contained ursolic acid and gentriacontan had also cytotoxic, however a little bit weaker effect. All changes observed were irreversible.     

Heat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide

Taxol, a plant-derived antitumor agent, stabilizes microtubules. Taxol also elicits cell signals in a manner indistinguishable from bacterial lipopolysaccharide (LPS). LPS-like actions of Taxol are controlled by the lps gene and are independent of binding to the known Taxol target, beta-tubulin. Using biotin-labeled Taxol, avidin-agarose affinity chromatography, and peptide mass fingerprinting, we identified two Taxol targets from mouse macrophages and brain as heat shock proteins (Hsps) of the 70- and 90-kDa families. Geldanamycin, a specific inhibitor of the Hsp 90 family, blocked the nuclear translocation of NF-kappaB and expression of tumor necrosis factor in macrophages treated with Taxol or with LPS. Geldanamycin did not block microtubule bundling by Taxol or macrophage activation by tumor necrosis factor. Thus, Taxol binds Hsps, and Hsp 90 helps mediate the activation of macrophages by Taxol and by LPS.     

Cartilage and collagenases

The articular cartilage is frequently destroyed in rheumatic diseases. Among the various responsible factors, enzymes and especially collagenases play a leading role. Their action explains the collagen degradation linked with cartilage destruction. The author recalls the origin, mechanism of action of the articular collagenases and discusses their role in the articular cartilage degradation in rheumatic diseases.     

The role of lecithin cholesterol acyltransferase and organic substances from coal in the etiology of Balkan endemic nephropathy: a new hypothesis.

Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p=0.02) and (p=0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population.     

Toll-like receptor 9: a new target of ischemic preconditioning in the brain.

Preconditioning with lipopolysaccharide (LPS), a toll-like receptor 4 (TLR4) ligand, provides neuroprotection against subsequent cerebral ischemic brain injury, through a tumor necrosis factor (TNF)alpha-dependent process. Here, we report the first evidence that another TLR, TLR9, can induce neuroprotection. We show that the TLR9 ligand CpG oligodeoxynucleotide (ODN) can serve as a potent preconditioning stimulus and provide protection against ischemic brain injury. Our studies show that systemic administration of CpG ODN 1826 in advance of brain ischemia (middle cerebral artery occlusion (MCAO)) reduces ischemic damage up to 60% in a dose- and time-dependent manner. We also offer evidence that CpG ODN preconditioning can provide direct protection to cells of the central nervous system, as we have found marked neuroprotection in modeled ischemia in vitro. Finally, we show that CpG preconditioning significantly increases serum TNFalpha levels before MCAO and that TNFalpha is required for subsequent reduction in damage, as mice lacking TNFalpha are not protected against ischemic injury by CpG preconditioning. Our studies show that preconditioning with a TLR9 ligand induces neuroprotection against ischemic injury through a mechanism that shares common elements with LPS preconditioning via TLR4.     

Hepatitis B virus infection among pregnant women in Split region

A seroepidemiologic survey of pregnant women in Split region was performed in order to determine a strategy for prenatal screening for HBsAg. Thirty (7.5%) of 400 women had the markers of past or current HBV infection, while 3/400 (0.75%) were carriers. According to demographic data and risk factors they represent low risk population. General prenatal screening for HBsAg is advisable.     

Interactions of clonidine and nifedipine in moderately severe hypertensive patients

In ten patients (age: 47-59 yr) with moderately severe essential hypertension, the humoral and hemodynamic effects of a 4-day therapy with 2 x 75 micrograms clonidine, 2 x 20 mg nifedipine (slow-release), and their combination were investigated and compared with baseline values. The following measurements were observed under clonidine (C), nifedipine (N), and on combination (C/N), respectively: heart rate fell significantly under C from a mean of 79 to 67/min (P less than .05), increased to 73/min after N (P greater than .05) and fell again to 68/min under combination (P less than .05). Systolic blood pressure (Riva-Rocci method) decreased from a mean of 184 to 171 (C), 168 (N) and 161 mm Hg (C/N), respectively (P less than .01). Diastolic blood pressure was also significantly altered (113 vs. 104 (C), 107 (N), and 100 mm Hg (C/N); P less than .05). Stroke volume (ECHO) was not altered significantly (77 vs. 71 (C), 79 (N), and 80 mL (C/N), respectively), whereas cardiac output dropped from 5.9 to 4.9 L/min (C; P less than .05), increased to 5.7 (N; P greater than .05), and dropped again to 5.3 L/min (C/N; P greater than .05). Peripheral vascular resistance increased from a mean of 2091 to 2297 (C), fell to 1933 (N), and increased again to 2138 dyn/sec/cm-5 (C/N). Plasma norepinephrine levels fell from 440 to 281 (C; P less than .01), increased to 391 (N; P greater than .05), and fell again to 404 pg/mL (C/N; P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)