In vivo antihyperlipidemic activity of a new series of N-(benzoylphenyl) and N-(acetylphenyl)-1-benzofuran-2-carboxamides in rats

A new series of N‐(benzoylphenyl) and N‐(acetylphenyl)‐1‐benzofuran‐2‐carboxamides ( 3a – 3d and 4a ′– 4c ′) were synthesized. Compounds ( 3a , 3b , and 4a ′– 4c ′) were tested in vivo using Triton‐WR‐1339‐induced hyperlipidemic rats as an experimental model for their hypolipidemic activity. The tested animals were divided into eight groups: control, hyperlipidemic, 3a , 3b , 4a ′, 4b ′, 4c ′, and bezafibrate. At a dose of 15 mg/kg, the elevated plasma triglyceride (TG) levels were significantly reduced in compounds 3b (p <0.0001) and 4c ′ (p <0.05) after 12 and 24 h compared to the normal control group. Furthermore, high‐density lipoprotein‐cholesterol levels were remarkably increased in compounds 3b (p <0.001) and 4c ′ (p <0.05). Meanwhile, compound 4b ′ slightly reduced the TG levels after 12 and 24 h. The present study demonstrated new properties of the novel series of benzofuran‐2‐carboxamides 3b and 4c ′ as potent lipid‐lowering agents. It is, therefore, reasonable to assume that compounds 3b and 4c ′ may have a promising potential in the treatment of hyperlipidemia and coronary heart diseases.     

Laminar Necrosis of Placental Membranes: A Histologic Sign of Uteroplacental Hypoxia

Laminar necrosis of placental membranes (LN), a band of coagulative necrosis at the choriodecidual interphase, is a histologic lesion of unclear pathogenesis that has been reported in placentas from preeclampsia, preterm premature rupture of membranes, and preterm abruption. To better explore other possible correlations of LN, we performed a retrospective case-control study in which data on pregnancy risks and outcomes, neonate conditions, and placental gross, routine microscopic, and selected immunohistochemistry examinations in 52 consecutive cases of LN were compared with 52 gestational age-matched control cases without LN. Maternal hypertensive disorders and combinations of 2 or more maternal, fetal, neonatal, or placental conditions known to be potentially associated with uteroplacental hypoxia were more prevalent in patients with LN than in control patients. By immunohistochemistry, LN areas were positive for complement 9 (marker of necrosis) and negative for active caspase 3 (marker of irreversible apoptosis), nitrotyrosine residues (marker of oxidative stress), and Ki-67 (proliferation marker), thus confirming their necrotic rather than apoptotic nature. However, LN areas were flanked by caspase 3 positivity, and the positivity for nitrotyrosine residues was more pronounced in the decidua and mesenchyme in the same membrane rolls as LN, which indicates a probable role of apoptosis and oxidative stress in the development of LN. Based on these immunohistochemical results and clinicopathologic correlations, we believe LN should be recognized and reported as a hypoxic placental lesion.Presented at the 9th Meeting of the International Federation of Placenta Associations; Mainz, Germany; September 24 to 27, 2003     

High spectral and spatial resolution MRI of age‐related changes in murine prostate

The purpose of this work was to evaluate high‐resolution echo‐planar spectroscopic MRI of normal and precancerous prostatic changes in a transgenic mouse line. Simian virus large T‐antigen transgenic male mice (N = 7, age = 34 ± 3.7 weeks) with prostatic hyperplasia and intraepithelial neoplasia (PIN) were studied. High spectral and spatial resolution (HiSS) MRI of the water proton signal was compared to the free induction decay (FID) integral image and conventional gradient‐echo and spin‐echo imaging. Water peak‐height images of the prostate produced from HiSS datasets showed improved contrast‐to‐noise ratio (CNR) (P < 0.03), and greater morphological detail (P < 0.004) based on texture analysis. Despite the high spectral resolution of the HiSS datasets, signal‐to‐noise ratio (SNR) compared favorably with that of the FID integral and conventional images. Lobular features in HiSS images of older mice were consistent with hyperplasia seen on histology. A partially deuterated water‐filled catheter was inserted in the mouse rectum for susceptibility matching between the colon interior and exterior to minimize image artifacts. These preliminary results suggest that HiSS MRI provides detailed morphology of the murine prostate and can detect early changes associated with the development of cancer. HiSS MRI of patients may have similar advantages. Magn Reson Med 60:575–581, 2008. © 2008 Wiley‐Liss, Inc.     

Interobserver and intraobserver reproducibility in digital and routine microscopic assessment of prostate needle biopsies

Advances in whole slide digital imaging in the past decade necessitate validation of these tools in each organ system in advance of clinical adoption. We assessed reproducibility in reporting prostate needle biopsy parameters among urologic pathologists using routine and digital microscopy in a consultation/second opinion-like setting. Four urologic pathologists evaluated a single core level from 50 diagnostically challenging needle biopsy specimens by routine microscopy and whole slide digital imaging. Interobserver and intraobserver agreement were calculated for primary and secondary Gleason grades, Gleason score, tumor quantitation (percentage and size in millimeters), and perineural invasion. Interobserver agreement for routine microscopy was excellent for primary Gleason grade (κ = 0.72) and good for all other parameters (κ ranging from 0.36 to 0.55). Whole slide digital imaging assessment yielded similar agreement for all parameters. Intraobserver agreement for primary Gleason grade and Gleason score was very good to excellent for all pathologists (all κ ≥ 0.65 and ≥ 0.73, respectively). Size of tumor in millimeters consistently displayed higher levels of agreement than percentage of tumor across media and pathologists. Digital assessment of routinely reported cancer parameters on prostatic needle biopsy for a given scanned core level is comparable to that of routine microscopy. These findings imply that histologic interpretation using dynamic whole slide images may accurately simulate routine microscopic evaluation in the consultation setting. Implementation of whole slide digital imaging in these scenarios may significantly reduce the workload of large referral centers in the near future and impact the manner in which pathologists seek second opinion consultation on challenging cases.     

The use of enzymatic biomarkers in two marine invertebrates Nereis diversicolor and Patella vulgata for the biomonitoring of Tangier's bay (Morocco)

The fast increase of anthropogenic activities has led to a continual influx of xenobiotics into the marine ecosystems. Quantifying biochemical parameters in marine invertebrates makes possible the evaluation of pollutants' damaging effect. In fact, to examine the health state of Tangier's bay, we focused on the study of catalase, esterase, acetylcholinesterase and alpha-amylase activities as biomarkers in two species of marine invertebrates Nereis diversicolor (Polychaeta, Nereidae) and Patella vulgata (Mollusca, Prosobranchia), collected from different sites along the Mediterranean coastline of Tangier. Our results showed that these biochemical parameters are disturbed following the level of decreasing environmental quality, and for this reason they are promising in the biomonitoring studies of the Moroccan marine environment.     

Do prostatic transition zone tumors have a distinct morphology?

Previous studies have proposed that the morphologic spectrum of prostatic glands of variable size with tall columnar cells displaying basally oriented nuclei and clear to pale pink cytoplasm (TZ-LOOK) is characteristic of the well to moderately differentiated component of transition zone (TZ) tumors. However, the specificity of these findings has not been well studied. In a recent report, we identified dominant peripheral zone (PZ) and TZ tumors situated anterior to the prostatic urethra. Currently, we evaluate the histopathologic features of 215 dominant tumors, including 63 TZ and 73 anterior PZ lesions and an additional cohort of 79 posterior PZ tumors, in radical prostatectomy specimens, to identify the prevalence of this morphology in tumors of different zonal origin. Each dominant tumor was assigned a TZ-LOOK extent score of 0 to 4, with 0 = no such morphology, 1 = 1% to 25%, 2 = 26% to 50%, 3 = 51% to 75%, and 4 = >75%. Overall, 121/215 (56%) tumors showed some degree of this histology, including 56 of 63 (89%) TZ tumors and 65 of 152 (43%) PZ tumors (P<0.0001). Thirty-seven of 215 (17%) lesions had scores of 3 to 4, with 31 (84%) of these being of TZ origin. However, only 31/63 (49%) TZ tumors had >50% TZ-LOOK. Among PZ tumors, 6/152 (4%) had predominant (>50%) TZ-LOOK morphology, yet 23/152 (15%) of all PZ tumors and 23/65 (35%) of PZ tumors displaying any degree of TZ-LOOK had scores of 2 to 3 (>25%; nonfocal). In tumors of both zones with predominant (scores 3 to 4; >50%) TZ-LOOK histology, darker glands of usual acinar adenocarcinoma was often seen at the periphery. Conversely, in tumors with nonpredominant TZ-LOOK (scores 1 to 2; 50% of this histology are very likely of TZ origin, but this scenario occurs in only half of TZ tumors. Importantly, the TZ-LOOK is nonfocal in up to 35% of PZ tumors exhibiting any degree of this morphology. Given this lack of specificity, caution should be exercised in assigning zone of origin based on this histologic appearance, especially in limited samples such as prostate needle biopsy.     

Lead in breastmilk samples from women living in the West Bank: a cross-sectional study

Background

Breastmilk is the recommended form of enteral nutrition for all infants. Infants nourishing on breastmilk contaminated with lead are at high risk of exposure to this neurotoxic heavy metal. The aim of this study was to screen lead concentrations in samples of breastmilk obtained from women living in three main regions of the West Bank and to investigate the sociodemographic characteristics associated with high lead concentrations.

Somatosensory mechanical response and digit somatotopy within cortical areas of the postcentral gyrus in humans: An MEG study

Somatosensory evoked fields in response to compression (termed as Co) and decompression (termed as De) of glabrous skin (D1, thumb; D2, index finger; D5, little finger) were recorded. Although estimated equivalent current dipoles (ECDs) following stimulation of D1 and D5 were larger, but not significantly larger, in decompression than in compression, those of D2 were significantly larger (P = 0.035). The ECDs were located in the postcentral gyrus in the order of D5De, D2De, and D1De medially, posteriorly, and superiorly in decompression but not in compression (z‐value, F = 2.692, P = 0.031). The average distance of ECDs between D1 and D5 was longer in decompression (12.8 ± 1.6 mm) than in compression (9.1 ± 1.6 mm). Our data suggest that the cortical response for the commonly used digit D2 is functionally different from those for other digits (D1 and D5) that the somatotopic variability is greater in compression. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Treatment Strategies for Residual Disease following Neoadjuvant Chemotherapy in Patients with Early-Stage Breast Cancer

Breast cancer continues to be the most diagnosed cancer among women worldwide. Neoadjuvant chemotherapy is the standard of care for breast cancer patients with locally advanced disease and patients with poor pathological features, such as triple-negative (TN) or human epidermal growth factor receptor-2 (HER2)-positive subtypes. Neoadjuvant therapy offers several advantages, including better surgical outcomes, early systemic treatment for micro-metastases, and accurate tumor biology and chemosensitivity assessment. Multiple studies have shown that achieving pathological complete response (pCR) following neoadjuvant chemotherapy is associated with better prognosis and better treatment outcomes; almost half of such patients may fail to achieve pCR. Tumor proliferative index, hormone receptor (HR) status, and HER2 expression are the major predictors of pCR. Strategies to improve pCR have been dependent on augmenting neoadjuvant chemotherapy with the addition of taxanes and dual anti-HER2 targeted therapy in patients with HER2-positive tumor, and more recently, immunotherapy for patients with TN disease. The clinical management of patients with residual disease following neoadjuvant chemotherapy varies and depends mostly on the level of HR expression and HER2 status. Recent data have suggested that switching trastuzumab to trastuzumab-emtansine (T-DM1) in patients with HER2-positive disease and the addition of capecitabine for patients with HER2-negative and HR-negative subtype is associated with a better outcome; both strategies are incorporated into current clinical practice guidelines. This paper reviews available and ongoing studies addressing strategies to better manage patients who continue to have residual disease following neoadjuvant chemotherapy.