Mechanism of action of a tyrphostin, 3,4-dihydroxy-α-cyanothiocinnamamide, in breast cancer cell growth inhibition involves the suppression of cyclin B1 and the functional activity of cyclin B1/p34cdc2 complex

Tyrphostins are a group of compounds specifically targeted for the inhibition of tyrosine phosphorylation in signal transduction pathways. We studied the effects of a tyrphostin, 3,4-dihydroxy--cyanothiocinnamamide (tyrphostin-47), on hormone-responsive MCF-7 and hormone-unresponsive MCF-7-5C cell growth by DNA analysis for a period of 10 days. The growth of both cell lines was inhibited by this drug at 50 and 100 µM concentrations. Flow cytometric analysis showed that tyrphostin treatment caused a significant delay in the progression of MCF-7 cells through Gl and S phases of the cell cycle. The level of cyclin B1, a component of the mitosis promoting factor (MPF), was reduced by 90% in the presence of 100 µM tyrphostin. The other component of MPF, p34cdc2 kinase, was not affected; however, its functional activity was dramatically reduced, as determined by histone H1 phosphorylation assay. In contrast, G1 cyclins (D1 and E) and tyrosine kinase activity were not markedly affected by tyrphostin-47, as determined by Western immunoblot detection with specific antibodies. Our results suggest that a possible mechanism of tyrphostin action in breast cancer cells might involve the suppression of cyclin B1 and inhibition of the functional activity of cyclin B1/p34cdc2 complex. Our data indicate that the cell cycle machinery might be a target for developing novel drugs for breast cancer.     

Periodontal findings in patients with oral submucous fibrosis and comet assay of affected gingival epithelial cells

Background: Oral submucous fibrosis (OSF) involves large sections of population and is related to certain chewing practices that involve direct exposure of the gingiva to noxious chemicals and additives. The impact of such practices, although studied extensively in relation to the cheek mucosa, is not elucidated as far as gingival tissues are concerned. The possible DNA damage on affected gingiva is also one of the objectives of the present study. Methods: One hundred cases of individuals with OSF and 89 without OSF were examined for periodontal parameters and compared. Biopsies of gingival tissue from both categories were examined with conventional hematoxylin and eosin staining for epithelial, connective tissue, and inflammatory changes. Comet assay of epithelial cells obtained from scraping the gingival surface of both patients with OSF and control individuals was performed . Results: Patients with OSF had poorer oral hygiene and greater loss of attachment, probing depth, and recession compared with controls. Significant histopathologic changes in the form of loss of rete ridges with gingival epithelium reduced to a flattened surface was observed. All the patients with OSF showed comet cells in larger numbers. The controls also showed comet cells but in fewer numbers, and the number of individuals showing comet cells was significantly less. Conclusion: OSF showed significant changes in affected gingiva, and the presence of comet cells in all the patients with OSF is a significant indicator of possible pathognomonic developments.     

Effect of Methadone Maintenance Treatment on Heroin Craving,a Literature Review

ABSTRACT

Despite agreement that methadone maintenance treatment (MMT) is an effective and safe option for treatment of heroin dependence, there have been controversies about its effect on heroin craving. A systematic literature review of the PubMed database was used to find studies eligible for inclusion in the study. The authors present the results of 16 articles that met all inclusion criteria. Overall, 7 studies reported that methadone could reduce heroin craving, 4 studies reported that patients in MMT are still at risk of having heroin craving, 1 study reported that methadone could increase heroin craving, and 4 studies reported that methadone has a neutral effect on heroin craving. One may speculate from these data that methadone may help with heroin craving, but patients in MMT may still be at risk of cue-induced heroin cravings. Methadone provides a helpful tool for reducing some components of craving and risk of relapse for patient receiving MMT.     

Hepatoprotective studies on Sida acuta Burm. f.

Ethnopharmacological relevance

Sida acuta Burm. f. (Malvaceae) is used in Indian traditional medicine to treat liver disorders and is useful in treating nervous and urinary diseases and also disorders of the blood and bile.

Aim of the study

Evaluation of the hepatoprotective properties of the methanolic extract of the root of Sida acuta (SA) and the phytochemical analysis of SA.

Materials and methods

The model of paracetamol-induced hepatotoxicity in Wistar rats, liver histopathological observations, hexobarbitone-induced narcosis and in vitro anti-lipid peroxidation studies were employed to assess the hepatoprotective efficacy of SA. Phytochemical assay of SA was conducted following standard protocols.

Results

Significant hepatoprotective effects were obtained against liver damage induced by paracetamol overdose as evident from decreased serum levels of glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, alkaline phosphatase and bilirubin in the SA treated groups (50, 100, 200 mg/kg) compared to the intoxicated controls. The hepatoprotective effect was further verified by histopathology of the liver. Pretreatment with Sida acuta extract significantly shortened the duration of hexobarbitone-induced narcosis in mice indicating its hepatoprotective potential. Phytochemical studies confirmed the presence of the phenolic compound, ferulic acid in the root of Sida acuta, which accounts for the significant hepatoprotective effects observed in the present study.

Conclusion

The present study thus provides a scientific rationale for the traditional use of this plant in the management of liver disorders.     

Circadian Body Temperature Variability is an Indicator of Poor Prognosis in Cardiomyopathic Hamsters

BackgroundLow body temperature is an independent predictor of poor prognosis in patients with congestive heart failure. The cardiomyopathic hamster develops progressive biventricular dysfunction, resulting in heart failure death at 9 months to 1 year of life. Our goal was to use cardiomyopathic hamsters to examine the relationship between body temperature and heart failure decompensation and death.Methods and ResultsTo this end, we implanted temperature and activity transducers with telemetry into the peritoneal space of 46 male Bio-TO-2 Syrian cardiomyopathic hamsters. Multiple techniques, including computing mean temperature, frequency domain analysis, and nonlinear analysis, were used to determine the most useful method for predicting poor prognosis. Data from 44 hamsters were included in our final analysis. We detected a decline in core body temperature in 98% of the hamsters 8 ± 4 days before death (P < .001). We examined the dominant frequency of temperature variation (ie, the circadian rhythm) by using cosinor analysis, which revealed a significant decrease in the amplitude of the body temperature circadian rhythm 8 weeks before death (0.28°C; 95% CI, 0.26-0.31) compared to baseline (0.36°C; 95% CI, 0.34-0.39; P = .005). The decline in the circadian temperature variation preceded all other evidence of decompensation.ConclusionsWe conclude that a decrease in the amplitude of the body temperature circadian rhythm precedes fatal decompensation in cardiomyopathic hamsters. Continuous temperature monitoring may be useful in predicting preclinical decompensation in patients with heart failure and in identifying opportunities for therapeutic intervention.     

Platelet activating factor: A potential biomarker in acute coronary syndrome?

Platelet activating factor (PAF) is a potent pro‐inflammatory negotiator that shows distinct spectrum of biological and pharmacological effects. Importantly, it participates in a wide range of pathophysiological conditions. In cardiovascular system, PAF has been shown to have an important role in platelet and neutrophil aggregation, vascular permeability, microvascular leakage, thrombus formation, leukocyte adhesion to the endothelial cells, and initiation and progression of atherosclerosis. The purpose of this article was to review the PAF, a family of lipids that is associated with the pathology of coronary artery diseases due to their association with leading etiological mechanisms such as inflammation, endothelial dysfunction, oxidative and nitrosative stress, and platelet reactivity. This review further provides information about PAF and its potential role as a key contributor to the pathogenesis of cardiovascular disorders.     

Onsite QTc Interval Screening for Patients in Methadone Maintenance Treatment

ABSTRACT

To improve the electrocardiogram screening process and early detection of patients at high risk for cardiac arrhythmias, the authors created a model in their clinic where they provided an onsite electrocardiogram screening that might be feasible and practical. The authors then performed a retrospective chart review to access the efficacy and feasibility of their new onsite procedure in identifying methadone maintained patients at high risk for cardiac arrhythmias. Records from all patients who are currently or had previously been maintained on methadone in the methadone maintenance program at the Atlanta VA Medical Center between 2002 and 2009 were evaluated. Of the 140 patients treated at the clinic between 2002 and 2009, 85 were excluded from the study because they had been treated as guests (had been in treatment in other clinics but received methadone dosing temporarily from our clinic), were treated in the clinic for less than 6 months, or dropped out of treatment. Thus, 55 patient charts were selected for review. Most patients (95%) received baseline and annual electrocardiogram screening. The average baseline QTc was (417 ± 30) and most recent QTc (442 ± 25). This QTc prolongation from baseline showed statistical significance (P < .0001). Sixty-seven percent of patients had statistically significant QTc prolongation from baseline but was less than 450 ms (mean: 428 ± 16, P = .008). Twenty-seven percent of patients had statistically significant QTc prolongation from baseline of more 450 ms but was less than 500 ms (mean: 460 ± 8, P < .0001). Six percent of patients had statistically significant QTc prolongation from baseline of more 500 ms (mean: 503 ± 1.15, P = .027). Recent cocaine use was the only individual variable that showed statistically significant correlation with QTc prolongation (F = 6.98, P = .01). The authors demonstrated in this study that providing an onsite electrocardiogram screening with a focus on patient education and limiting the referral to specialty care for patients at high risk for cardiac arrhythmias could be practical and feasible.