Cutaneous and subcutaneous lymphatic drainage of the breast

The aim of this study was to topographically map the superficial lymphatic drainage of the breast. The study was performed on 24 female cadavers. Patent blue dye was administered intradermally and subcutaneously. After visualization and dissection of the lymphatics, a schematic record of their routes was made on a transparency folio of the breast map. Afterwards, a summation was performed of all schematic records, and a map of the lymphatic vessels of the breast was derived. The natural dominant drainage for the outflow of lymph from the superficial areas of the breast is to the axillary nodes. This pathway plays a primary role in the initial stages of breast cancer. This observation does not exclude other pathways of lymph drainage, which probably play a secondary role except in cases where flow is limited in the primary lymphatic pathway. Although each quadrant is dominantly drained by one or two of its own collectors, it is also interconnected via the subareolar plexus with the other quadrants of the breast, and lymph collectors of the upper medial quadrant pass to the lower medial quadrant and vice versa. Lymphatic collectors from the medial quadrants followed the medial, cranial and caudal margins of the breast and afterwards ran into the axilla. The common interconnections of the individual quadrants of the breast with one or two collectors, which circumscribe the breast, but run outside the subareolar plexus, further increase the risk of developing locoregional recurrences. In some cases, the marginal lymphatic collectors of the breast may even run beyond the anatomical boundaries of the breast--particularly apparent in the submammary region.     

Cytochrome P450 destruction by benzene metabolites 1,4-benzoquinone and 1,4-hydroquinone and the formation of hydroxyl radicals in minipig liver microsomes.

Reactive metabolites of benzene 1,4-benzoquinone and 1,4-hydroquinone exert their toxic effects through covalent and/or oxidative damage to DNA and proteins. Since minipigs have been proposed as a suitable model species in toxicological and pharmacological research, the aim of this study was to explore mechanisms by which catechol, 1,4-hydroquinone and 1,4-benzoquinone destroy cytochrome P450 (P450) and induce oxidative stress in minipig liver microsomes. Our second goal was to assess the usefulness of minipig liver microsomes as a model system for the testing of the production of oxidative stress by clinically relevant quinone-containing compounds, e.g. anthracyclines. Of the three benzene metabolites tested, the highest P450 destruction was caused by 1,4-benzoquinone. This destructive effect did not correlate with the production of hydroxyl radicals as measured by ESR spin trapping which was the highest in samples containing 1,4-hydroquinone. Our results confirm previous findings that 1,4-benzoquinone exerts its effect mainly by direct attack on macromolecules while 1,4-hydroquinone rather stimulates the production of reactive oxygen species. Doxorubicin stimulated the production of hydroxyl radicals and the destruction of P450 similarly as 1,4-hydroquinone. Minipig liver microsomes should be further tested as a possibly suitable model system for the testing of potential modulators of the toxicity of doxorubicin.     

A mark release-recapture study to define the flight behaviors of Anopheles vestitipennis and Anopheles albimanus in Belize, Central America

The recapture rates of wild-caught, unengorged Anopheles vestitipennis and Anopheles albimanus females were determined at 0, 400, and 800 m from a fixed release point in Belize, Central America. Three sampling trials, each consisting of two 12-hour collections, were performed at each distance during September-October 2003. A total of 1,621 An. vestitipennis and 1,326 An. albimanus were marked and released during the course of the study. The recapture rate of An. vestitipennis was greatest at 0 m (7.9%; 44/ 556) and declined from 3.0% (16/531) at 400 m to 0.2% (1/534) at 800 m. Anopheles albimanus females were recaptured only at the 0-m distance and in extremely low numbers (1.1%; 5/446). Biting patterns for the unmarked natural populations were similar to those previously described for Belize, and recaptures for both species occurred during these normal biting times. The overall recapture rates for An. vestitipennis (3.76%; 61/ 1,621) and An. albimanus (0.38%; 5/1,326) indicate that An. vestitipennis has a higher probability of being attracted to a human habitation.     

Inflammation and genes

Inflammation is a protective immune response to infection, trauma, or injury; however, only a subset of patients develops inflammation, suggesting other contributing factors involved, such as the environment and genes. Inflammation-associated genes involving those with pro- and anti-inflammatory effect should be properly balanced and regulated; the protein products of these genes ultimately determine the outcome of inflammation. Apart from gene mutations, gene polymorphisms related to some inflammatory markers also appear to correlate with the incidence and/or outcome of serious inflammatory events. Some genes recently recognized to be associated with inflammation are briefly reviewed. Modern genomic approaches, such as DNA micro-arrays and serial analysis of gene expression, allow for determining the extremely complex profile of inflammatory genes.     

Direct administration of rutin does not protect against catecholamine cardiotoxicity

High levels of catecholamines are cardiotoxic and may trigger acute myocardial infarction (AMI). Similarly, the synthetic catecholamine isoprenaline (ISO) evokes a pathological state similar to AMI. During AMI there is a marked increase of free iron and copper which are crucial catalysts of reactive oxygen species formation. Rutin, a natural flavonoid glycoside possessing free radical scavenging and iron/copper chelating activity, may therefore be potentially useful in reduction of catecholamine cardiotoxicity as was previously demonstrated after its long-term peroral administration. Male Wistar:Han rats received rutin (46 or 11.5 mg kg(-1) i.v.) alone or with necrogenic dose of ISO (100 mg kg(-1) s.c.). Haemodynamic parameters were measured 24h after drug application together with analysis of blood, myocardial content of elements and histological examination. Results were confirmed by cytotoxicity studies using cardiomyoblast cell line H9c2. Rutin in a dose of 46 mg kg(-1) aggravated ISO-cardiotoxicity while the dose of 11 mg kg(-1) had no effect. These unexpected results were in agreement with in vitro experiments, where co-incubation with larger concentrations of rutin significantly augmented ISO cytotoxicity. Our results, in contrast to previous studies in the literature, suggest that the reported positive effects of peroral administration of rutin were unlikely to have been mediated by rutin per se but probably by its metabolite(s) or by some other, at this moment, unknown adaptive mechanism(s), which merit further investigation.     

Incidence of pericardial effusion in females stimulated in "in vitro fertilization" program

AIMS: To evaluate the incidence of pericardial irritation in females after hormonal stimulation in in vitro fertilization program, and to set its clinical significance as a symptom of ovarian hyperstimulation syndrome (OHSS). PATIENTS: Thirty-nine females, aged 30 +/- 5 years (20-46), with a normal echo finding prior to hormonal stimulation. METHODS: Serial echocardiography: baseline A, in hCG application B, embryo-transfer C. RESULTS: Thirty-nine, 39, and 35 echocardiography examinations were done on A, B, and C respectively. On B, in 7 (17.9%) of 39 patients either new pericardial effusion "1," increased pericardial echogenicity "2," or both "3" were detected (4 patients, 2 patients, and 1 patient, i.e., 10.3%, 5.1%, and 2.6% respectively.). On C, in 8 of 35 patients (22.8 %) abnormalities were detected: "1" in 2 patients (5.7 %), "2" in 1 patient (2.9 %), and "3" in 5 patients (14.2 %). No clinical symptoms related to these findings were present. No OHSS occurred in these patients. On the contrary, clinical OHSS developed later in 2 patients, classified as medium degree (1 patient) and severe degree (1 patient)-both patients had negative echo during follow-up. CONCLUSION: Echocardiographic signs of mild pericardial irritation may appear also in patients with no clinical signs of OHSS. The incidence of these changes increases during stimulation procedure. Development of OHSS may not be preceded by the incidence of these warning signs. Consequently, routine echocardiographic examination during stimulation is not indicated, since significant pericardial effusion is rather a late sign of OHSS.