Breast cancer lymphoscintigraphy: Factors associated with sentinel lymph node non visualization.

OBJECTIVE: To evaluate factors associated with non identification of the sentinel lymph node (SLN) in lymphoscintigraphy of breast cancer patients and analyze the relationship with SLN metastases. MATERIAL AND METHODS: A single-center, cross-sectional and retrospective study was performed. Forty patients with lymphoscintigraphy without sentinel lymph node identification (negative lymphoscintigraphy - NL) were enrolled. The control group included 184 patients with SLN identification (positive lymphoscintigraphy - PL). Evaluated factors were age, body mass index (BMI), tumor size, histology, localization, preoperative breast lesion hookwire (harpoon) marking and SLN metastases. The statistical analysis was performed with uni- and multivariate logistic regression models and matched-pairs analysis. RESULTS: Age (p=0.036) or having BMI (p=0.047) were the only factors significantly associated with NL. Being ≥60 years with a BMI ≥30 increased the odds of having a NL 2 and 3.8 times, respectively. Marking with hookwire seems to increase the likelihood of NL, but demonstrated statistical significance is lacking (p=0.087). The other tested variables did not affect the examination result. When controlling for age, BMI and marking with the harpoon, a significant association between lymph node metastization and NL was not found (p=0.565). CONCLUSIONS: The most important factors related with non identification of SLN in the patients were age, BMI and marking with hook wire. However, only the first two had statistical importance. When these variables were controlled, no association was found between NL and axillary metastases.

In vivo hydroquinone exposure impairs allergic lung inflammation in rats.

Hydroquinone (HQ) is naturally found in the diet, drugs, as an environmental contaminant and endogenously generated after benzene exposure. Considering that HQ alters the immune system and its several source of exposures in the environment, we hypothesized that prolonged exposure of HQ could affect the course of an immune-mediated inflammatory response. For this purpose, male Wistar rats were intraperitoneally exposed to vehicle or HQ once a day, for 22 days with a 2-day interval every 5 days. On day 10 after exposure with vehicle or HQ, animals were ovalbumin (OA)-sensitized and OA-aerosolized challenged on day 23. HQ exposure did not alter the number of circulating leukocytes but impaired allergic inflammation, evidenced by lower number of leukocytes in the bronchoalveolar lavage fluid 24h after OA-challenge. Reduced force contraction of ex vivo tracheal segments upon OA-challenge and impaired mesentery mast cell degranulation after in situ OA-challenge were also detected in tissues from HQ exposed animals. The OA-specificity on the decreased responses was corroborated by normal trachea contraction and mast cell degranulation in response to compound 48/80. In fact, lower levels of circulating OA-anaphylactic antibodies were found in HQ exposed rats, as assessed by passive cutaneous anaphylaxis assay. The reduced level of OA-anaphylactic antibody was not dependent on lower number or proliferation of lymphocytes. Nevertheless, lower expression of the co-stimulatory molecules CD6 and CD45R on OA-activated lymphocytes from HQ exposed rats indicate the interference of HQ exposure with signaling of the humoral response during allergic inflammation. Together, these data indicate specific effects of HQ exposure manifested during an immune host defense.

Are Drosophila SR drive chromosomes always balanced?

SR chromosomes are the best-known case of sex chromosome meiotic drive. These X chromosomes cause the production of female-biased progenies in several Drosophila species. Due to their meiotic drive advantage, they are expected to spread and become fixed, resulting in population extinction due to the lack of males. However, this apparently does not occur: SR chromosomes are maintained in balanced polymorphisms, resulting from the equilibrium between their meiotic drive advantage and deleterious fitness effects. In this paper we review the current explanations for their deleterious effects and we argue that it is highly improbable that all newly emerged SR are sufficiently deleterious to avoid fixation. Unbalanced SR almost certainly arise and go unnoticed because of three possible outcomes: (i) fixation followed by extinction of the population or species; (ii) fixation followed by the emergence and fixation of drive suppressors, restoring the normal 1:1 sexual proportion; or (iii) transformation into balanced SR due to partial suppression. If these outcomes really occur, then extant cases of sex-chromosome meiotic drive such as SR, causing small deviations on the population sexual proportion, are only the tip of the iceberg and strong sexual proportion shifts (possibly followed by extinction) are a more common feature of species evolution than is usually assumed.

Polymorphism for Y-linked suppressors of sex-ratio in two natural populations of Drosophila mediopunctata.

In several Drosophila species there is a trait known as "sex-ratio": males carrying certain X chromosomes (called "SR") produce female biased progenies due to X-Y meiotic drive. In Drosophila mediopunctata this trait has a variable expression due to Y-linked suppressors of sex-ratio expression, among other factors. There are tow types of Y chromosomes (suppressor and nonsuppressor) and two types of SR chromosomes (suppressible and unsuppressible). Sex-ratio expression is suppressed in males with the SRsuppressible/Ysuppressor genotype, whereas the remaining three genotypes produce female biased progenies. Now we have found that approximately 10-20% of the Y chromosomes from two natural populations 1500 km apart are suppressors of sex-ratio expression. Preliminary estimates indicate that Ysuppressor has a meiotic drive advantage of 6% over Ynonsuppressor. This Y polymorphism for a nonneutral trait is unexpected under current population genetics theory. We propose that this polymorphism is stabilized by an equilibrium between meiotic drive and natural selection, resulting from interactions in the population dynamics of X and Y alleles. Numerical simulations showed that this mechanism may stabilize nonneutral Y polymorphisms such as we have found in D. mediopunctata.

Synthesis, stereochemical analysis, and neuromuscular blocking activity of oximino ether derivatives of progesterone.

This study consists of the synthesis, separation, and stereochemical analysis of oximino ethers, followed by a preliminary pharmacological evaluation for neuromuscular blockade. Synthesis of the compounds began with the double oximation of progesterone, which yielded EE and ZE dioximes as major products. Both stereoisomers were separated and purified by chromatography followed by crystallization. The diether of each dioxime was prepared by O-alkylation with 2-dimethylaminoethyl chloride hydrochloride, using a mixture of potassium tert-butoxide and sodium hydride as base. The diethers were separated from the monoethers by vacuum chromatography. Configurational assignments of all compounds were based on 1HNMR and 13CNMR spectroscopy. Quaternization with methyl bromide yielded the salts which were purified via fractional crystallization. A preliminary pharmacological evaluation was conducted by using mice on a treadmill apparatus. Structure-activity relationships are discussed on the basis of similarities to succinylcholine.