Increased expression of transferrin receptors and iron in amoeboid microglial cells in postnatal rats following an exposure to hypoxia

This study was aimed to ascertain the effects of hypoxia on regulation of iron in the brain of newborn rats. At 3 h and 1 day after hypoxic exposure transferrin receptor expression as detected immunohistochemically with the antibody OX-26, and the iron content as shown by Perls' staining of amoeboid microglial cells was markedly increased. The induced changes, however, were not evident at 10 min and in longer surviving rats killed at 3 and 7 days. It is suggested that the upregulation of transferrin receptor expression coupled with iron uptake by amoeboid microglial cells in the periventricular regions is a protective mechanism to facilitate the sequestration of excess iron that may have been released either from the iron-rich oligodendrocytes, or accumulated due to a disruption of its normal transportation following the hypoxic insult. This would help protect the brain from harmful effects of iron.     

Chronic suppurative otitis media and sensorineural hearing loss: Is there a correlation?

Traditionally, it has been accepted that chronic suppurative Otitis media is associated with a breakdown in meekanical conduction of sound leading to conductive hearing loss, On;the contrary, there are two schools of thought when it come, to the issue of cpchlear involvement leading to sensorineural hearing loss (SNIIL) in chronic suppura the Otitis media. The present study was undertaken to find out whether a sensorineural component exists in hearing loss associated with chronic suppurative otitis media, A sample of 100 patients of unilateral chronic suppurative otitis media was selected for the Study and their bone conduction thresholds Mere analyzed in relation to the duration of disease using audiometric data. A 24 per cent incidence of sensoineural hearing loss was found in this series, garticularly involving the higher frequencies. Moreover, the incidence of sensorineural hearing loss progressively increased with the increase in duration of chonic suppurative Ouns meadia     

Antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: an orally bioavailable heat shock protein 90 modulator.

PURPOSE: The purpose of this study was to investigate the antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG; NSC707545), a water-soluble benzoquinone ansamycin. EXPERIMENTAL DESIGN: The activity of 17-DMAG, in vivo, was evaluated for inhibition of fibroblast growth factor (FGF)-2-induced angiogenesis in s.c. implanted Matrigel in mice. In vitro, the activity of 17-DMAG on endothelial cells (human umbilical vein endothelial cells; HUVEC) was tested in FGF-2; and vascular endothelial growth factor (VEGF)-induced proliferation and apoptosis, motility, and extracellular matrix invasion; and on the alignment of capillary like structures in Matrigel. The protein level of heat shock protein (Hsp)90 and client proteins was examined by Western blot in FGF-2 and VEGF-stimulated HUVEC. RESULTS: Daily oral administration of 17-DMAG affected the angiogenic response in Matrigel in a dose-dependent manner. The hemoglobin content in the Matrigel implants was significantly inhibited, and the histological analysis confirmed a decrease of CD31(+) endothelial cells and of structures organized in cord and erythrocyte-containing vessels. In vitro, the compound inhibited dose-dependently the migration and the extracellular matrix-invasiveness of HUVEC and their capacity to form capillary like structures in Matrigel. 17-DMAG treatment also inhibited FGF-2 and VEGF-induced HUVEC proliferation and resulted in apoptosis. Accordingly, the expression of Hsp90 direct client proteins (pAkt and c-Raf-1) or their downstream substrates including pERK was also affected. 17-DMAG consistently increased the expression of Hsp70. Throughout the study similar results were obtained with 17-allylamino-17-demethoxygeldanamycin (17-AAG; NSC330507), the analog compound currently undergoing clinical trials. CONCLUSIONS: We show that the Hsp90 targeting agents 17-DMAG and 17-AAG inhibit angiogenesis. The strong effects on endothelial cell functions, in vitro, indicate that the antiangiogenic activity of 17-DMAG/17-AAG could also be due to a direct effect on endothelial cells. The oral bioavailability of 17-DMAG might be of advantage in investigating the potential of this compound in clinical trials with antiangiogenic as well as antiproliferative endpoints.     

Relationship of mammographic parenchymal patterns to breast cancer risk factors and smoking in Alaska Native women.

The purpose is to determine breast cancer risk factors and correlates of mammographic parenchymal patterns among Alaska Native women. A retrospective review was performed of mammograms and mammogram records among 528 sequential screening mammogram examinations performed in Anchorage, Alaska. Mammogram density was classified by American College of Radiology (Breast Imaging Reporting and Data System) density patterns 1-4 (fat-->dense) and by percent density. Clinical data, including risk factors, ethnic group (Indian, Aleut, or Eskimo), and smoking status were obtained. Results were analyzed by univariate and multivariate analyses. Of 528 women, 164 were Indian, 155 were Aleut, and 209 were Eskimo. Mean age at first birth was lower and parity higher compared with published data in white women. Breast cancer risk factors were similar across ethnic groups. In multivariate analysis, patient age, parity, hormone replacement therapy, hysterectomy, and history of biopsy were associated, and smoking was not associated with density scores. Aleut and Indian women were less likely to have high-density mammograms than were Eskimo women (P = 0.0448). No significant differences were found between ethnic group for conventional breast cancer risk factors. Mammogram density was associated with age at screening, parity, hormone replacement therapy, hysterectomy, history of biopsy, and ethnicity but not smoking status. Eskimo women had higher mammogram density than Aleuts or Indians.     

Phase II study of paclitaxel and cisplatin for advanced urothelial cancer

PURPOSE: We examined the role of paclitaxel and cisplatin as first line therapy for metastatic urothelial cancer. MATERIALS AND METHODS: A total of 34 patients were enrolled in this study, and all were eligible for treatment and assessable for response. Patients received 135 mg./m.2 paclitaxel intravenously for 3 hours followed by 70 mg./m.2 cisplatin for 2 hours every 3 weeks to a maximum of 6 cycles. RESULTS: Of the patients 70% experienced a major response to treatment, which was partial/regression in 38% and complete in 32%. Toxicity was manageable with no episodes of grade 4 leukopenia or thrombocytopenia. Nonhematological toxicities included primarily nausea, anorexia and neuropathy, which rarely were severe. CONCLUSIONS: This regimen of paclitaxel and cisplatin is effective, safe and convenient to administer in an outpatient setting for advanced urothelial cancer.     

Standardized extract of Lactuca sativa Linn. and its fractions abrogates scopolamine-induced amnesia in mice: A possible cholinergic and antioxidant mechanism

Objectives: The present study was designed to evaluate the efficacy of Lactuca sativa (LS) Linn. (Asteraceae) against scopolamine-induced amnesia and to validate its traditional claim as memory enhancer.

Methods: Ethanol extract of fresh LS leaves (LSEE), standardized on the basis of quercetin content, was successively partitioned using various solvents viz., hexane, ethyl acetate, and n-butanol in increasing order of polarity. LSEE (50, 100, and 200?mg/kg) and its various fractions (at a dose equivalent to dose of LSEE exhibiting maximum activity), administered orally for 14 days, were evaluated for their memory enhancing effect against scopolamine-induced (1?mg/kg, i.p.) amnesia in 3–4 months old male Laca mice (n?=?6 in each group). The memory enhancing effect was evaluated using behavioural (elevated plus maze, novel object recognition and Morris water maze tests) and biochemical parameters (acetylcholinesterase activity, malonaldehyde, superoxide dismutase, nitrite, catalase, and reduced gultathione content). The results of the test substances were compared with both scopolamine and donepezil that was used as a standard memory enhancer and acetylcholinesterase inhibitor.

Results: Scopolamine elicit marked deterioration of memory and alteration in biochemical parameters in comparison to the control group. LSEE and its n-butanol and aqueous fractions significantly (P?n-butanol fraction (15?mg/kg) exhibited maximum anti-amnesic effect among various tested dose levels.

Discussion: The results exhibited that LS prophylaxis attenuated scopolamine-induced memory impairment through its acetylcholinesterase inhibitory and antioxidant activity validating its traditional claim.     

Histological and immunohistochemical study of estrogen and progesterone receptors in normal human breast tissue in adult age groups vulnerable to malignancy

Analysis of receptor status has become standard procedure for assessing breast cancer patients. Estrogen causes epithelial proliferation in breast tissue via the estrogen receptor (ER). The progesterone receptor (PR) is also regulated by the estrogen gene. Analyzing ER and PR together gives information regarding the likely response of carcinoma patients to hormonal therapy. The aim of the present study was to record the expression patterns of ER and PR in normal mammary tissue in different age groups to provide reference data to facilitate histological diagnosis. Breast tissues from the upper outer quadrant of each side of 27 adult female cadavers were examined after H & E staining. ER and PR were identified and examined by immunohistochemistry. The percentage area occupied by parenchyma relative to stromal tissue was calculated in different age groups and was about 4:6, 3.5:6.5, 3:7, 2:8, and 1.5:8.5 in the 3rd, 4th and 5th, 6th, 7th, 8th and 9th, and 10th decades of life, respectively. Both ER and PR were present in all age groups and the numbers of both receptors were maximal during the 4th decade. The distribution and staining patterns for both ER and PR were recorded in different age groups. The contiguous pattern of ER, which is considered pathognomonic of breast carcinoma, was not seen except in one case in the 6th decade. Moderately stained ER and PR receptor sites predominated throughout. The study of normal breast tissue of similar age might provide comparisons that will help histopathologists to make clinical diagnoses from breast biopsies. Clin. Anat. 29:729–737, 2016. © 2016 Wiley Periodicals, Inc.     

The Self-Overlap Method for Assessment of Lung Nodule Morphology in Chest CT

Surface morphology is an important indicator of malignant potential for solid-type lung nodules detected at CT, but is difficult to assess subjectively. Automated methods for morphology assessment have previously been described using a common measure of nodule shape, representative of the broad class of existing methods, termed area-to-perimeter-length ratio (APR). APR is static and thus highly susceptible to alterations by random noise and artifacts in image acquisition. We introduce and analyze the self-overlap (SO) method as a dynamic automated morphology detection scheme. SO measures the degree of change of nodule masks upon Gaussian blurring. We hypothesized that this new metric would afford equally high accuracy and superior precision than APR. Application of the two methods to a set of 119 patient lung nodules and a set of simulation nodules showed our approach to be slightly more accurate and on the order of ten times as precise, respectively. The dynamic quality of this new automated metric renders it less sensitive to image noise and artifacts than APR, and as such, SO is a potentially useful measure of cancer risk for solid-type lung nodules detected on CT.