Study of daunorubicin cardiotoxicity prevention with pyridoxal isonicotinoyl hydrazone in rabbits.

Risk of cardiotoxicity is the most serious drawback of the clinical usefulness of anthracycline antineoplastic antibiotics, which however, remain among the most powerful and widely employed anticancer drugs. In this study we have used daunorubicin-induced cardiomyopathy in rabbits as a model to investigate possible cardioprotective effects of pyridoxal isonicotinoyl hydrazone (PIH)-a principal representative of a novel group of aroylhydrazone iron chelators. Three groups of animals were used: a control group (n=11; i.v. saline), daunorubicin-treated animals (n=11; 3mg/kg, i.v.), and animals pretreated with PIH (n=9, 25 mg/kg, i.p.) 60 min before daunorubicin administration. All substances were administered once weekly for 10 weeks. Repeated administration of daunorubicin caused premature death in four animals and induced conspicuous histopathological changes in the myocardium, progressive and significant impairment of systolic heart function (a decrease in left ventricular dP/dt(max), ejection fraction, an increase in the pre-ejection period/left ventricular ejection time index), and a gradual increase in cardiac troponin T plasma concentrations. On the contrary, all the PIH-treated animals have survived all daunorubicin applications. Furthermore, in this group, the daunorubicin-induced cardiac changes were in most functional, biochemical as well as morphological parameters less pronounced than in the group receiving daunorubicin alone. Hence, PIH and other aroylhydrazones merit further investigation as potentially protective agents against anthracycline-induced cardiotoxicity.     

The usefulness of ovarian volume, antral follicle count and age as predictors of menopausal status.

OBJECTIVE: To compare the accuracy of ovarian volume, antral follicle count and age in predicting menopausal status in healthy women. METHODS: The cross-sectional study was set in the Gynecology Division at the Leonor Mendes de Barros Maternity Hospital, S?o Paulo, Brazil. The subjects of this study were premenopausal (n = 121) and postmenopausal (n = 71) healthy women aged between 40 and 55 years. They were submitted to a medical interview and transvaginal ultrasound examination. The ovarian volume (cm3), antral follicle count and chronological age were recorded in both groups and the accuracies of these parameters in predicting menopausal status were compared. RESULTS: Premenopausal women presented larger ovaries than postmenopausal women (p < 0.01). Premenopausal women had a higher number of antral follicles than postmenopausal women (p < 0.01). The receiver operating characteristic curves showed that ovarian volume, age and antral follicle count had similar sensitivities and specificities in predicting menopausal status. The best cut-off points were observed when ovarian volume was <4 cm3, age was > or =48 years and antral follicle count was < or = two follicles. CONCLUSIONS: Ovarian volume, antral follicle count and chronological age are all individually predictive of menopausal status, with similar accuracies.     

Needlescopic thoracic sympathectomy: treatment for palmar hyperhidrosis

BACKGROUND: Open thoracic sympathectomy has been the established option for patients with essential hyperhidrosis. Recently, video-assisted endoscopic sympathectomy has provided a simple, safe, reliable, and cost-effective alternative to the earlier technique. With advances in instrumentation, performing the procedure through 2-mm and 3-mm needlescopic ports is now possible. The authors evaluate the effectiveness of so-called needlescopic thoracic sympathectomy for the treatment of primary hyperhidrosis. METHODS: Thirty five consecutive patients with a mean age of 24 years, including 23 men and 12 women, underwent bilateral needlescopic thoracic sympathectomies at the National University Hospital of Singapore. RESULTS: The mean operative duration was 56 minutes, and the mean hospital stay was 1.2 days. In no patient did Horner's syndrome or significant pneumothorax develop. The rate of success, defined as completely dry hands, was 97%. Two patients had unilateral recurrences that responded well to repeat needlescopic sympathectomies. We performed a total of 72 sympathectomies. CONCLUSIONS: Our study demonstrates that the use of miniature port access sites produces excellent medical and cosmetic results and is associated with a short hospital stay and low risk of complications.     

Permeabilisation and solubilisation of soybean phosphatidylcholine bilayer vesicles, as membrane models, by polysorbate, Tween 80.

To understand better the wide-spread pharmaceutical use of non-ionic surfactant Tween 80 (TW), the colloidal properties of the surfactant alone and in combinations with the common phospholipid, phosphatidylcholine (PC), were studied. Static and dynamic light scattering revealed that TW solubilises PC at TW/PC approximately 2.75/1 mol/mol and that TW micelle disintegration occurs on time-scale of 2.5 min, independent of amphipath concentration. This is up to nearly 300-times faster than the TW caused dissolution of PC containing unilamellar vesicles. The apparent dissolution time of TW/PC mixed aggregates, in contrast, decelerates from >700 min to <5 min upon increasing starting total amphipath concentration, with thermal activation energy > or =24 (< or =80) kJ mol(-1). The aggregate dissolution rate in highly concentrated TW/PC suspensions reflects the dissolved polysorbate-aggregate exchange rate (approximately 6.7 x 10(-3)s(-1)) rather than TW flip-flop rate across a bilayer (>0.2 min(-1)). PC solubilisation proceeds linearly with the square-root of time, and is kinetically governed by the speed of surfactant diffusion through the bulk (D approximately 2.8 x 10(-11)m2 s(-1)). Creation of small Tween-phosphatidylcholine mixed micelles is typically preceded by pre-solubilisation structures, first in the form of deformable, strongly fluctuating, bilayer vesicles and then of elongated, presumably thread-like, mixed micelles. TW/PC mixed micelles become smaller with growing surfactant/lipid molar ratio, whereas TW/PC mixed vesicles become more and more leaky with increasing surfactant concentration. Our results highlight the molecular and kinetic aspects of polysorbate-membrane interactions and provide a rationale for the popularity of Tween surfactants in pharmaceutical products: such surfactants can solubilise fatty molecules and bilayer membranes but need quite a long time for this, which is available in pharmaceutical preparations but normally not in vivo; this makes Tweens relatively efficient and safe. Furthermore, our data could help design better ultra-deformable mixed lipid-surfactant vesicles for the non-invasive transdermal drug delivery across the skin.     

Laryngopyocele: signs on computed tomography

A laryngocele is an air-filled dilation of the saccule of the larynx. An infected laryngocele is called a laryngopyocele. Our experience with a case of laryngopyocele with signs on computed tomography before and after antibiotic therapy is presented since laryngopyocele is more unusual.     

Sanguinarine and chelerythrine: assessment of safety on pigs in ninety days feeding experiment.

Sanguinaria canadesis, Chelidonium majus and Macleya cordata have been used for centuries as alternative medicines. Currently the extracts from these medicinal plants are components of veterinary and human phytopreparations, and of oral-hygiene agents. Sanguinarine and chelerythrine (SA/CHE) are biologically active components of these extracts. They display distinct antibacterial and anti-inflammatory properties, but, on the other hand, they have been reported as having adverse effects - genotoxicity and hepatotoxicity. This paper is aimed at evaluation of the effects of daily administration of the extract from Macleya cordata (2 mg and 100 mg in 1 kg feed, sanguinarine:chelerythrine 3:1) in the diet on the health status of swine. After 90-day administration, alkaloids were retained to a different extent in tissues. The highest SA/CHE retention was detected in the gingiva (0.55 microg/g) and liver (0.15 microg/g), no SA/CHE were detected in muscles. Plasma SA levels attained 0.11 microg/ml. Treated animals did not display any results of hematological, biochemical or histological assay different from controls. A (32)P-postlabeling assay proved that no DNA-adducts with SA/CHE were detected in pig livers. We did not observe any symptom linked to epidemic dropsy syndrome often attributed to sanguinarine. In conclusion, an average daily oral dose of alkaloids up to 5 mg per 1 kg animal body weight proved to be safe.     

The effect of cholate on solubilisation and permeability of simple and protein-loaded phosphatidylcholine/sodium cholate mixed aggregates designed to mediate transdermal delivery of macromolecules.

Carriers for non-invasive administration of biologically important antioxidant enzymes Cu,Zn-superoxide dismutase (SOD) and catalase (CAT) were developed. Solubilisation and permeabilities of various soybean phosphatidylcholine/sodium cholate (SPC/NaChol) mixtures, mainly in the form of lipid bilayers, focussing on system properties relevant for non-invasive enzyme delivery were investigated in this work. Static and dynamic light scattering measurements gave information on the behaviour of the systems containing up to 40 mM NaChol and 30.6-1.2 mM SPC in the final suspension. The average size of such mixed aggregates was in the 100-200 nm range. Suspension turbidity decreased by 50% upon increasing nominal molar detergent/lipid ratio to NaChol/SPC = 7 and 1.25, in case of SPC = 1.2 and 19.6 mM, respectively. The effective NaChol/SPC molar ratio in bilayers saturated with the detergent was found to be: R(e)(sat) = 0.70 +/- 0.01; bilayer solubilisation point corresponded to R(e)(sol) = 0.97 +/- 0.02, independently of enzyme loading. Vesicles became very permeable to SOD when membrane bound NaChol concentration exceeded 13.7 mM, in case of total starting lipid concentration of 138 mM diluted to SPC = 19.6 mM. Specifically, we measured a 50% loss of SOD from the vesicles with an aggregate-associated molar detergent ratio NaChol/SPC approximately 0.7, which is near the saturation but well below the solubilisation limit. Calcein efflux from such vesicles was compared with SPC/NaChol/SOD mixed aggregates. Our results should contribute to the future design of vesicle mediated transdermal delivery of antioxidant enzymes.     

Laryngeal mask for intubation (Fastrach)

The laryngeal mask for intubation (MLI), or "Fastrach", is a new device designed by Brain for airway management. The MLI, a modified version of the conventional laryngeal mask, allows for blind intubation through the device using endotracheal tubes up to 8 mm in diameter. Insertion with the head in a neutral position makes this system useful for managing the airway when neck injury is present. The device has been used successfully in patients assessed as having difficult-to-manage airways and its use in emergencies inside or outside the hospital is promising. The MLI has been used with high rates of success in combination with other techniques such as fiberoptic bronchoscopy (success rate 99 to 100%) and transillumination (95 to 100% success rate) in patients whose airways have been considered difficult to manage. Given such high rates of success for MLI placement (95 to 100%) and for blind orotracheal intubation (81 to 100%), the Fastrach may offer an alternative to the conventional laryngeal mask in algorithms for airway management.