Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study

BACKGROUND: Human papillomavirus 16 (HPV16) has a number of variants, each with a different geographic distribution and some that are associated more often with invasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants. METHODS: Cervical samples were collected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV classes and subclasses were identified by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor characteristics were also collected. All statistical tests were two-sided. RESULTS: HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically significantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects for either E or AA variants, chi2 test). However, the frequency of AA variants was 21 times higher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P =.006, chi2 test). The odds ratio (OR) for cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/- standard deviation]) were 7.7 years younger than E-positive case patients (53.9 +/- 12.2 years) (P =.004, Student's t test). AA variants were associated with squamous cell carcinomas and adenocarcinomas, but E variants were associated with only squamous cell carcinomas (P =.014, Fisher's exact test). CONCLUSIONS: The high frequency of HPV16 AA variants, which appear to be more oncogenic than E variants, might contribute to the high incidence of cervical cancer in Mexico.     

Structure-activity relationships for the analgesic activity of gallic acid derivatives

Values of ID50 for a collection of structurally-related gallic acid derivatives have been employed to create a predictive quantitative structure-activity relationship (QSAR) which links structure to values of analgesic activity. The QSAR model developed has substantial predictive power for the design of novel gallic acid derivatives having improved analgesic potency.     

Antinociceptive properties of N-aryl-glutaramic acids and N-aryl-glutarimides

This study describes the antinociceptive activity of some N-aryl-glutaramic acids and N-aryl-glutarimides in writhing and formalin tests, two classical models of pain in mice. These compounds show high activity, being more active than acetyl salycilic acid, acetaminophen and indomethacin, used as standard drugs for comparison. The introduction of different substituent groups in the aromatic ring caused a significant change in activity. The results obtained here are promising from a pharmacological point of view, since these simple compounds might be used as models to obtain new and potent analgesic drugs.     

Pharmacological activity and chemical composition of callus culture extracts from selected species of Phyllanthus

This study was conducted in order to determine the chemical composition and the possible antinociceptive effects in mice of some species of Phyllanthus in vitro. The methanolic extracts obtained from callus cultures of P. fraternus, P. stipulatus and P. caroliniensis caused significant inhibition in to the late phase of the formalin test, whereas the extract from P. urinaria inhibited both neurogenic and inflammatory phases of the test. Conventional chromatographic methods (TLC, GC) permitted the detection of some steroids or triterpenes, including beta-sitosterol, glochidonol and glochidone, which seem be responsible for the antinociceptive effects of the callus extracts studied.     

Octyl and dodecyl gallates induce oxidative stress and apoptosis in a melanoma cell line

This study investigated the mechanism of cytotoxicity of octyl (G8) and dodecyl (G12) gallates in a murine melanoma cell line (B16F10). For this purpose, several methods to measure cell viability were used to determine if the cytotoxicity induced by these gallates corresponds to a general or an organelle-specific effect. Furthermore, the mechanisms related to apoptosis were examined, by studying the caspase-3 activity, oxidative stress, mitochondrial potential and the expression of anti- or proapoptotic proteins. When comparing the various methods of assessing cell viability, the tested gallates showed a higher cytotoxicity in the assay that indicates lysosomal activity, compared with the assays that indicate mitochondrial and ribosomal activities. Both gallates promoted the release of lactate dehydrogenase into the medium, indicating an effect on cell membrane integrity. The gallates also promoted cellular oxidative stress, mitochondrial depolarization and an increase in caspase-3 activity. Furthermore, the gallates induced an increase in proapoptotic (Bax) and a decrease in antiapoptotic (Bcl-2) proteins expression. Our results indicate that the apoptotic cell death induced by G8 and G12 in B16F10 cells involves lipid membrane damages, lysosomal and mitochondrial dysfunction, which was accompanied by alterations in apoptotic proteins expression and seems to be triggered by cellular oxidative stress.     

The mechanisms underlying the relaxant effect of methyl and ethyl gallates in the guinea pig trachea in vitro: contribution of potassium channels

The relaxant response and the possible contribution of K+ channels to the relaxation caused by both methyl and ethyl gallates, two compounds isolated from the Brazilian medicinal plant Phyllanthus urinaria, were investigated in the guinea pig trachea in vitro. Both methyl and ethyl gallate (0.01-30 microM) caused graded and complete relaxation of the guinea pig trachea without epithelium, pre-contracted by histamine, with mean EC50 values of 1.8 (1.2-2.2) microM and 0.7 (0.6-0.8) microM, respectively, and Emax of both 100+/-0%. Response to ethyl, but not methyl gallate, was significantly shifted to the right, with no change in the maximum effect when the epithelium was removed. The increase in K+ concentration in the medium to 80 mM completely abolished the relaxant response caused by both methyl and ethyl gallate. In addition, tetraethylammonium (10 mM) reduced by 50+/-6% and 43+/-4% the relaxation caused by methyl and ethyl gallates. In contrast, glibenclamide (3 microM) shifted (by about two- and fourfold) the concentration-response curves for both methyl and ethyl gallates, with no changes in the maximum effect. Charybdotoxin (100 nM), but not apamin (100 nM), significantly blocked by 54+/-5% and 59+/-4% the relaxation of both methyl and ethyl gallates. In contrast, SQ 22536 (10 microM; a selective adenylyl cyclase inhibitor), methylene blue (10 microM) or ODQ (1 microM; a guanylyl cyclase inhibitor) did not significantly affect the relaxant response caused by either of the compounds. These results provide evidence that the relaxation caused by both methyl and ethyl gallates in the guinea pig trachea in vitro may involve the activation of large-conductance Ca2+-activated K+ channels, and, to a lesser extent, ATP-sensitive K+ channels. Such results extend our previous observations and are consistent with the notion that methyl and ethyl gallates are mainly responsible for the relaxant action previously demonstrated in the extract of this plant.     

Effects of Sebastiana schottiana Extracts on Isolated Smooth Muscle Contraction.

Crude aqueous-ethanol, chloroform, and semipurified flavonoid-glycoside extracts of SEBASTIANA SCHOTTIANA (Euphorbiaceae) inhibited contractions of rat uterus to acetylcholine or oxytocin and guinea pig ileum to electric field stimulation. The greatest antispasmodic potency was observed with the chloroform extract. The popular use of this plant in Southern Brazil as a remedy for kidney or bladder calculi may be related to the presence of smooth muscle relaxing compounds.     

Platelet count and MPV,routinely measured but ignored parameters used in conjunction with the diagnosis of acute coronary syndrome: single study center in Iranian population, 2010

Background

Myocardial infarction is the major cause of morbidity and mortality in industrialized countries. Platelet count and the mean platelet volume (MPV), a simple and reliable indicator of platelet size which correlates with platelet activation, might associate with troponin in acute chest pain.

Methods

We analyzed MPV of 851 patients who were admitted to Rasoul-e-Akram Hospital with acute chest pain during the year 2010. Two blood samples were taken from each patient within 4 hours of their arrival for routine hematology, including platelet count and MPV, and cardiac troponin T. Also, electrocardiograms of the patients were recorded. Association of MPV and platelet count with troponin was observed.

Results

The patients in troponin positive group, who had also ischemic electrocardiographic changes, had higher MPV values than non- acute coronary syndrome (ACS) patients with normal cardiac troponin T levels (9.9 vs 9.5 fl with p< 0.001). In troponin negative group, the mean of platelet count was higher than that in the positive group (221683 vs 198814/µl with p< 0.001).

Conclusion

MPV and platelet count are inexpensive laboratory tests which can be measured in association with other laboratory biomarkers in patients presenting with acute chest pain.This could help to lower hospitalization rates and also avoid misdiagnosis and having complications of patients with ACS.