Phytoestrogens and indicators of breast cancer prognosis.

Breast cancer incidence is lower and survival is longer in Asian women residing in Japan, China, or the Philippines than Caucasian women residing in the United States. Phytoestrogen intake has been examined as a possible reason for the disparity in breast cancer incidence and survival. This study examined the association between phytoestrogen intake prior to diagnosis of breast cancer and indicators of breast cancer prognosis (tumor size, estrogen and progesterone receptor status, histological grade, lymphovascular invasion, nodal spread, and stage) in 128 women, aged 40-79 yr, newly diagnosed with invasive breast cancer. After controlling for significant confounding factors, higher intakes of phytoestrogens were associated with favorable indicators of breast cancer. In women with higher intakes of phytoestrogens, there was a 32% reduction in the odds of being diagnosed with any stage of cancer other than stage 1 (95% confidence interval, CI = 0.49-0.93; P = 0.02), a 38% reduction in odds of being diagnosed with positive lymphovascular invasion (95% CI = 0.40-0.95; P = 0.03), and a 66% increase in the odds of being diagnosed with a positive progesterone receptor (95% CI = 1.06-2.58; P = 0.03). We conclude that phytoestrogen intake prior to diagnosis may improve prognosis of breast cancer.

Quantitative determination of alginic acid in pharmaceutical formulations using capillary electrophoresis.

A capillary electrophoresis (CE) method has been developed and validated for the quantitative determination of alginic acid, which is used as a rafting agent in complex antacid formulations. The method involves a preliminary separation of the alginic acid from the formulation by washing the sample matrix with methanol, diluted HCl and water. This is followed by electrophoresis within a fused silica capillary using borate/boric acid buffer as the electrolyte, and the quantification is performed by a UV detector monitoring at 200 nm, where the intrinsic absorption of alginic acid is measured. An assay precision of better than 3% was achieved in intra- and interday determinations. No interference was found from the matrix of the antacid formulations.

Capillary gas chromatography determination of benzaldehyde arising from benzyl alcohol used as preservative in injectable formulations.

A simple, precise and accurate capillary gas-liquid chromatographic procedure has been developed to determine benzaldehyde, the toxic oxidation product of the widely used preservative and co-solvent benzyl alcohol, in injectable formulations of the non-steroidal anti-inflammatory drugs, diclofenac and piroxicam, as well as in Vitamin B-complex injection solutions. Following liquid-liquid extraction with chloroform, separation and quantification are achieved on a fused silica capillary column (25 m x 0.53 mm i.d.) coated with 0.5 microm film of OV-101. 3-Chlorobenzaldehyde was used as internal standard with flame-ionization as the detection mode. The ability of the system to resolve benzaldehyde peak from interfering components is good. The method displays excellent linearity over the concentration range 0.5-100 microg/ml of benzaldehyde and a precision of better than 2.5% from intra- and inter-day analyses. The quantification limit for benzaldehyde is 0.4 microg/ml. Levels of benzaldehyde in generic diclofenac and piroxicam injection formulations were found to be seven to 15 times higher than in reference formulations, and double in generic Vitamin B-complex injection formulations.

Polarographic determination of benzaldehyde in benzyl alcohol and sodium diclofenac injection formulations.

A rapid and sensitive polarographic method was developed for qualitative as well as quantitative analysis of the neurotoxic contaminant benzaldehyde in Na-diclofenac injections and in benzyl alcohol used for parental formulations. A well-defined differential pulse (DP) polarographic peak or a sampled direct current (SDC) wave was obtained at -1.39 V (vs. silver-silver chloride reference electrode) in Britton-Robinson buffer (pH 9.15) and at -1.41 V in 0.1 M LiCl solution. The reduction step involves a two-electron process, corresponding to the formation of benzyl alcohol. No peaks were observed in the anodic branch of the cyclic voltammogram, emphasizing the occurrence of an irreversible process. The peak current versus concentration relationship was found to be linear up to 50 microg/ml with the detection limit of 10 ng/ml and quantitation limit of 30 ng/ml. The relative standard deviations (S.D.) obtained for concentration levels of benzaldehyde as low as 25 microg/ml with the SDC and DP methods were 1.5 and 0.78% (n=10), respectively. Benzyl alcohol and Na-diclofenac are not electrochemically active, and metabisulfite reductions at -0.664 and -1.240 V do not interfere with the benzaldehyde reduction peak. The proposed methods (DP and SDC polarography) have been applied satisfactorily to the determination of benzaldehyde traces in benzyl alcohol and in different pharmaceutical products such as Na-diclofenac injectable formulations.

A RP-LC method with evaporative light scattering detection for the assay of simethicone in pharmaceutical formulations.

A reversed-phase liquid chromatographic method has been developed and validated for the determination of the polydimethylsiloxane (PDMS) component of Simethicone, which is used as an anti-foaming agent in pharmaceutical formulations. The method involves acidification to neutralise antacid components of the formulation, then a single extraction of the PDMS with dichloromethane. This is followed by separation with a reversed-phase column using an acetonitrile-chloroform solvent gradient, and quantification by an evaporative light scattering detector. An assay precision of 3% was achieved in intraday and interday determinations. No interference was found from the aluminium and magnesium hydroxide components of antacid formulations.

Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management.

The interaction of sunlight with drug medication leads to photosensitivity responses in susceptible patients, and has the potential to increase the incidence of skin cancer. Adverse photosensitivity responses to drugs occur predominantly as a phototoxic reaction which is more immediate than photoallergy, and can be reversed by withdrawal or substitution of the drug. The bias and inaccuracy of the reporting procedure for these adverse reactions is a consequence of the difficulty in distinguishing between sunburn and a mild drug photosensitivity reaction, together with the patient being able to control the incidence by taking protective action. The drug classes that currently are eliciting a high level of adverse photosensitivity are the diuretic, antibacterial and nonsteroidal anti-inflammatory drugs (NSAIDs). Photosensitising chemicals usually have a low molecular weight (200 to 500 Daltons) and are planar, tricyclic, or polycyclic configurations, often with heteroatoms in their structures enabling resonance stabilisation. All absorb ultraviolet (UV) and/or visible radiation, a characteristic that is essential for the chemical to be regarded as a photosensitiser. The photochemical and photobiological mechanisms underlying the adverse reactions caused by the more photoactive drugs are mainly free radical in nature, but reactive oxygen species are also involved. Drugs that contain chlorine substituents in their chemical structure, such as hydrochlorthiazide, furosemide and chlorpromazine, exhibit photochemical activity that is traced to the UV-induced dissociation of the chlorine substituent leading to free radical reactions with lipids, proteins and DNA. The photochemical mechanisms for the NSAIDs that contain the 2-aryl propionic acid group involve decarboxylation as the primary step, with subsequent free radical activity. In aerated systems, the reactive excited singlet form of oxygen is produced with high efficiency. This form of oxygen is highly reactive towards lipids and proteins. NSAIDs without the 2-arylpropionic acid group are also photoactive, but with differing mechanisms leading to a less severe biological outcome. In the antibacterial drug class, the tetracyclines, fluoroquinolones and sulfonamides are the most photoactive. Photocontact dermatitis due to topically applied agents interacting with sunlight has been reported for some sunscreen and cosmetic ingredients, as well as local anaesthetic and anti-acne agents. Prevention of photosensitivity involves adequate protection from the sun with clothing and sunscreens. In concert with the preponderance of free radical mechanisms involving the photosensitising drugs, some recent studies suggest that diet supplementation with antioxidants may be beneficial in increasing the minimum erythemal UV radiation dose.