Spectrophotometric analysis of raloxifene hydrochloride in pure and pharmaceutical formulations

Two simple and sensitive spectrophotometric methods (A and B) for the determination of raloxifene hydrochloride in bulk samples and pharmaceutical formulations are described. Method A is based on the oxidation of the drug with ferric chloride and coupling with potassium ferric cyanide. Method B is based on reduction of the drug with Fehling's reagent. Bluish green color formed in method A absorbs at 735 nm and brown color produced in method B absorbs at 430 nm.     

Regulation of the immune response by SHIP

Multiple lines of experimental data indicate that SHIP1 is an important negative regulator of the immune system. SHIP1 has been demonstrated to control survival and proliferation, as well as differentiation. In the cases of some inhibitory receptors, such as Fc gamma RIIB1, the molecular mechanisms of control by SHIP1 are established. For other receptors, particularly activating receptors where SHIP1 appears to set activation thresholds, the mechanisms remain to be discovered. Further study on SHIP and other SHIP family members could be critical for our understanding the negative regulation in multiple hematopoietic lineages and the immune system as a whole.     

Early operable breast cancer in elderly women treated with an aromatase inhibitor letrozole as sole therapy

Background:

Primary endocrine therapy (PET) with aromatase inhibitors (AIs) is an option in elderly patients unfit for or unwilling to undergo surgery. We studied the outcome of patients treated with letrozole as PET.

Methods:

Patients with early oestrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer treated with letrozole from February 2001 to September 2009 were reviewed. Inoperable and locally advanced tumours were excluded. Reasons for offering PET, response, survival, cause of death, time to initial and best response, fracture incidence, and late failure rates were studied.

Results:

In all, 104 patients received PET due to frailty (n=48), comorbidity (n=30), old age (n=9), and patient preference (n=17). Median follow-up was 56 months (4–106). Eighty-five cancers responded to letrozole (stable disease (SD, n=19), reduction in size (PR, n=42), and complete response ((CR), n=24)). Median survival was 51 months (4–103), time to initial response (PR/CR) 4.5 months (2–24), and time to best response 8.5 months (3–50). Letrozole was stopped in 25 patients due to progressive disease (n=19), side effects (n=5), and patient choice (n=1). Only 12 of 49 deaths were from breast cancer.

Conclusion:

Letrozole is a reasonable alternative in elderly women with early ER/PR-positive invasive breast cancer who are unfit or unwilling to undergo standard therapy.     

Specific detection of fungal pathogens by 18S rRNA gene PCR in microbial keratitis

Background  

The sensitivity and specificity of 18S rRNA polymerase chain reaction (PCR) in the detection of fungal aetiology of microbial keratitis was determined in thirty patients with clinical diagnosis of microbial keratitis.     

The multiple faces of RAGE – opportunities for therapeutic intervention in aging and chronic disease

Introduction: This review focuses on the multi-ligand receptor of the immunoglobulin superfamily – receptor for advanced glycation endproducts (RAGE). The accumulation of the multiple ligands of RAGE in cellular stress milieux links RAGE to the pathobiology of chronic disease and natural aging.

Areas covered: In this review, we present a discussion on the ligands of RAGE and the implications of these ligand families in disease. We review the recent literature on the role of ligand–RAGE interaction in the consequences of natural aging; the macro- and microvascular complications of diabetes; obesity and insulin resistance; autoimmune disorders and chronic inflammation; and tumors and Alzheimer’s disease. We discuss the mechanisms of RAGE signaling through its intracellular binding effector molecule – the formin DIAPH1. Physicochemical evidence of how the RAGE cytoplasmic domain binds to the FH1 (formin homology 1) domain of DIAPH1, and the consequences thereof, are also reviewed.

Expert opinion: We discuss the modalities of RAGE antagonism currently in preclinical and clinical studies. Finally, we present the rationale behind potentially targeting the RAGE cytoplasmic domain–DIAPH1 interaction as a logical strategy for therapeutic intervention in the pathological settings of chronic diseases and aging wherein RAGE ligands accumulate and signal.     

Preventive action of food seasoning spices mixture on fructose-induced lipid abnormalities

High fructose feeding in rats induces insulin resistance, hyperinsulinemia, hyperglycemia and dyslipidemia. The present study was undertaken to determine the hypolipidemic effect of food seasoning spices mixture on fructose-fed insulin resistant rats. Male Wistar rats received a daily diet containing either 60% fructose or 60% starch. They were administered with the spices mixture at three different doses (10 mg, 30 mg or 50 mg/day/rat) orally 15 days later. At the end of 45 days of the experimental period fructose-fed rats displayed elevated plasma glucose and insulin levels and dyslipidemia which included elevated levels of cholesterol, triglycerides, free fatty acids, reduced high density lipoprotein cholesterol and increased very low density lipoprotein cholesterol. Alterations in tissue lipid levels were also observed. Simultaneous treatment with spices mixture along with fructose diet resulted in the normalization of plasma glucose and insulin levels and restoration of lipid levels in plasma and tissues. The insulin potentiating action of the active principles in these spices may contribute to the hypolipidemic effect of spices mixture in high fructose-fed rats.     

Assessment of 8-oxo-7,8-dihydro-2′-deoxyguanosine as a marker of oxidative DNA damage in gasoline filling station attendants

Objectives

The urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) was used as a biomarker of oxidative DNA damage. The urinary 8-oxodG levels in petrol filling station attendants (exposed) at various petrol bunks were estimated as well as in the unexposed (cashier) population.

Materials and Methods

A total of 100 workers (79 petrol fillers and 21 cashiers) aged from 20 to 41 years participated in the study. An informed consent was taken from each participant. Information on personal habits and health was obtained through a questionnaire. After shifts, urine samples were collected analyzed for 8-oxodG using enzyme-linked immunosorbent assay (ELISA).

Results

Fifty-three percent of workers were in the 21–30 years age group. The maximum level of 8-oxodG was observed in the age group ≥ 41 years and the minimum in the age group of 31–40 years. The maximum level of 8-oxodG was observed among those workers who had ≥ 21 years of experience. The concentrations of 8-oxodG were significantly higher in petrol fillers than those in cashiers (p < 0.05).

Conclusions

Despite the conflicting results obtained in our study it was shown that 8-oxodG is related to chemical exposure. Further research is needed embracing a bigger number of participants to highlight the correlations between the exposure and the effects.     

Effect of vitamin E TPGS on immune response to nasally delivered diphtheria toxoid loaded poly(caprolactone) microparticles

The nasal mucosa has many advantages as a potential site for drug and vaccine delivery. The present study has sought to exploit this route of delivery using microparticles composed of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly(caprolactone) for nasal immunisation with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS-PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system.