Raman spectroscopy for the determination of coating uniformity of tablets: assessment of product quality and coating pan mixing efficiency during scale-up

Spray coating is an important unit operation in the pharmaceutical industry. The quality, stability, safety, and performance of the final product depend largely on the amount and uniformity of coating applied. Raman spectroscopy is used to develop a multivariate quantitative model using tablets collected from different stages of coating. Subsequently, the calibration is used for the determination of coating progress in small-scale batches. The method developed is used as a process analytical technology tool to assess the desired product quality attributes in commercial scale equipment. Insight into the mixing efficiency is gained by examining intra-tablet variability using the Raman method.     

Up-regulation of estrogen receptors by nonsteroidal antiestrogens in human breast cancer

Development of resistance to hormonal therapy in breast cancer is frequently associated with a decline or loss of cellular estrogen receptors. Agents which up-regulate the receptor may reduce the incidence of hormonal resistance. Antiestrogens at concentrations ranging from 0.1 to 1 microM produced a 2- to 4-fold increase of estrogen receptors in MCF-7 and T-47D breast cancer cells. This increase, which occurred as early as 3 h and was sustained throughout the 4 days of continuous exposure to tamoxifen, was primarily due to an enhancement in receptor synthesis.     

Ankle-brachial index and subclinical cardiac and carotid disease: the multi-ethnic study of atherosclerosis

The authors studied associations between ankle-brachial index (ABI) and subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis. Participants included 3,458 women (average age = 62.6 years) and 3,112 men (average age = 62.8 years) who were free of clinically evident cardiovascular disease. Measurements included ABI, carotid artery intima-media thickness, and coronary artery calcium assessed with computed tomography. Five ABI categories were defined: <0.90 (definite peripheral arterial disease (PAD)), 0.90-0.99 (borderline ABI), 1.00-1.09 (low-normal ABI), 1.10-1.29 (normal ABI), and > or =1.30 (high ABI). Compared with that in men with normal ABI, significantly higher internal carotid artery intima-media thickness was observed in men with definite PAD (1.58 vs. 1.09; p < 0.001), borderline ABI (1.33 vs. 1.09; p < 0.001), and low-normal ABI (1.18 vs. 1.09; p < 0.001) after adjustment for confounders. Fully adjusted odds ratios for a coronary artery calcium score greater than 20 decreased across progressively higher ABI categories in both women (2.85 (definite PAD), 1.27 (borderline ABI), 1.11 (low-normal ABI), 1.00 (normal ABI; referent), and 0.78 (high ABI); p for trend = 0.0002) and men (3.26 (definite PAD), 1.72 (borderline ABI), 1.14 (low-normal ABI), 1.00 (normal ABI; referent), and 1.43 (high ABI); p for trend = 0.0002). These findings indicate excess coronary and carotid atherosclerosis at ABI values below 1.10 (men) and 1.00 (women) and may imply increased risk of cardiovascular events in persons with borderline and low-normal ABI.     

The effect of short-term cyclophosphamide on estrogen therapy in metastatic breast cancer

Stimulation of tumor growth and induced hypercalcemia both may occur during the initiation of estrogen therapy in breast cancer. This study was conducted to determine whether cyclophosphamide (CTX) as an adjuvant to estrogen therapy might (1) prevent induced hypercalcemia or (2) achieve a higher tumoricidal effect during the phase of tumor stimulation. Fifty postmenopausal women with inoperable or recurrent disseminated breast carcinoma were divided into two random groups. Results could be evaluated in 44 patients; 21 received diethylstilbestrol (DES), and 23 received DES plus a 4-week course of cyclophosphamide (DES + CTX). The response rate was 5/21 (24%) in the DES group and 8/23 (35%) in the DES + CTX group (p > 0.05). The median duration of response for both groups was 9 months. The survival rate at 24 months was 52% in the DES group and 25% in the DES + CTX group (p = 0.05). Induced hypercalcemia occurred in 3 patients treated with DES + CTX. Short-term cyclophosphamide adjuvant to estrogen therapy did not prevent induced hypercalcemia nor prolong the duration of response or survival.     

Comparison of low risk and higher risk profiles in middle age to frequency and quantity of coronary artery calcium years later

Little is known about the relation of having favorable levels of all major cardiovascular risk factors (low risk [LR]) earlier in life to coronary artery calcium (CAC) later in life. From 2002 to 2003, CAC was compared in participants aged >60 years who were LR (n = 42) with those not LR (n = 39) at baseline (from 1967 to 1973). Despite adverse changes in risk factors, the prevalence of measurable CAC and mean CAC scores were less for LR participants than for non-LR participants (60% vs 77%, p = 0.09, and 217 vs 443, p = 0.05, respectively).