Antiproliferative effects of several compounds isolated from Amburana cearensis A. C. Smith

Amburana cearensis a common tree found in Northeastern Brazil is widely used in folk medicine. The present work evaluated the cytotoxicity of kaempferol, isokaempferide, amburoside A and protocatechuic acid isolated from the ethanol extract of the trunk bark of A. cearensis. The compounds were tested for their cytotoxicity on the sea urchin egg development, hemolysis assay and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay using tumor cell lines. Isokaempferide and kaempferol, but not amburoside A and protocatechuic acid, inhibited the sea urchin egg development as well as tumor cell lines, but in this assay isokaempferide was more potent than kaempferol. Protocatechuic acid was the only compound able to induce hemolysis of mouse erythrocytes, suggesting that the cytotoxicity of kaempferol and isokaempeferide was not related to membrane damage.     

Reference Ranges for Uterine Artery Pulsatility Index during the Menstrual Cycle: A Cross-Sectional Study

Background

Cyclic endometrial neoangiogenesis contributes to changes in local vascular patterns and is amenable to non-invasive assessment with Doppler sonography. We hypothesize that the uterine artery (UtA) impedance, measured by its pulsatility index (PI), exhibits a regular pattern during the normal menstrual cycle. Therefore, the main study objective was to derive normative new day-cycle-based reference ranges for the UtA-PI during the entire cycle from days 1 to 34 according to the isolated time effect and potential confounders such as age and parity.

Methods

From January 2009 to December 2012, a cross-sectional study of 1,821 healthy women undergoing routine gynaecological ultrasound was performed. The Doppler flow of the right and left UtA-PI was studied transvaginally by colour and pulsed Doppler imaging. The mean right and left values and the presence or absence of a bilateral protodiastolic notch were recorded. Reference intervals for the PI according to the cycle day were generated by classical linear regression.

Results

The majority of patients (97.5%) presented unilateral or bilateral UtA notches. The crude 5th, 50th, and 95th reference percentile curves of the UtA-PI at 1–34 days of the normal menstrual cycle were derived. In all curves, a progressive significant decrease occurred during the first 13 days, followed by an increase and recovery in the UtA-PI. The adjusted 5th, 50th, and 95th reference percentile curves for the effects of age and parity were also obtained. These two conditions generated an approximately identical UtA-PI pattern during the cycle, except with small but significant reductions at the temporal extremes.

Conclusions

The median, 5th, and the 95th percentiles of the UtA-PI decrease during the first third of the menstrual cycle and recover to their initial values during the last two thirds of the cycle. The rates of decrease and recovery depend significantly on age and parity.     

Mitochondrial Dynamics Protein Drp1 Is Overexpressed in Oncocytic Thyroid Tumors and Regulates Cancer Cell Migration

Oncocytic cell tumors are characterized by the accumulation of morphologically abnormal mitochondria in their cells, suggesting a role for abnormal mitochondrial biogenesis in oncocytic cell transformation. Little is known about the reason for the dysmorphology of accumulated mitochondria. The proteins regulating the morphology of mitochondria, the "mitochondria-shaping" proteins, can modulate their size and number; however, nothing is known hitherto about a possible involvement of mitochondrial dynamics in oncocytic cell transformation in tumors. Our aim was to assess the status of the mitochondria morphology and its role in oncocytic cell transformation. We therefore evaluated the expression pattern of the main mitochondrial fusion and fission proteins in a series of thyroid cell tumor samples, as well as in thyroid tumor cell lines, with and without oncocytic cell features. The expression of mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1 and Fis1) proteins were evaluated by immunohistochemistry (IHC) in a series of 88 human thyroid tumors. In vitro studies, for comparative purposes and to deepen the study, were performed using TPC1 - a papillary thyroid carcinoma derived cell line—and XTC.UC1, an oncocytic follicular thyroid carcinoma-derived cell line. Both IHC and in vitro protein analyses showed an overall increase in the levels of "mitochondrial-shaping" proteins in oncocytic thyroid tumors. Furthermore, overexpression of the pro-fission protein Drp1 was found to be associated with malignant oncocytic thyroid tumors. Interestingly, genetic and pharmacological blockage of Drp1 activity was able to influence thyroid cancer cells’ migration/invasion ability, a feature of tumor malignancy. In this study we show that unbalanced mitochondrial dynamics characterize the malignant features of thyroid oncocytic cell tumors, and participate in the acquisition of the migrating phenotype.     

The High Prevalence of Low HDL-Cholesterol Levels and Dyslipidemia in Rural Populations in Northwestern China

Background

Dyslipidemia is a major health problem in China and an important modifiable cardiovascular disease (CVD) risk factor. This study aimed to describe the prevalence of dyslipidemia and low high density lipoprotein cholesterol (HDL-cholesterol) and associated risk factors among adults in rural northwest China.

Methods

In a cross-sectional analyses involving 2,980 adults aged >18 years, information on the demographics, cigarette smoking, alcohol consumption, education, and medical history was collected via face-to-face interviews. Blood samples were collected to determine total cholesterol (TC), low-density lipoprotein cholesterol (LDL-cholesterol), and HDL-cholesterol, and triglycerides (TG) levels.

Results

The prevalence of high TC, high LDL-cholesterol, low HDL-cholesterol, and high TG were 1.0%, 0.6%, 60.9%, and 13.7%, respectively. TC, LDL-cholesterol, and TG increased with age in females. Elevated TC was more common in females than in males. The prevalence of low HDL-cholesterol was 67.6% in males and 55.4% in females. Current smokers, those with less education, those who were overweight or obese, and those with large waist circumference were more likely to have low HDL-cholesterol (p<0.05). Multivariable regression showed that male gender showed an association with low HDL-cholesterol (OR 2.10, 95%CI 1.68–2.61), age ≥60 years (OR 0.80, 95% CI 0.64–0.99), BMI (BMI = 24–27.9, OR 1.27, 95%CI 1.04–1.54, p = 0.02 and BMI≥28, OR 1.56, 95%CI 1.10–2.20, p = 0.01) and enlarged waist circumference (OR 2.10, 95%CI 1.51–2.92). Non-alcohol drinker was associated with low HDL-cholesterol levels (OR 0.72, 95%CI 0.53–0.99, p = 0.04).

Conclusions

This study found that the prevalence of low HDL-cholesterol was 67.6% and 55.4% for males and females. Male gender, non-alcohol drinker, BMI and central obesity were important risk factors for low HDL-cholesterol in Chinese adults.     

Presence of Cryptosporidium spp. and Giardia duodenalis in Drinking Water Samples in the North of Portugal

Cryptosporidium and Giardia are 2 protozoan parasites responsible for waterborne diseases outbreaks worldwide. In order to assess the prevalence of these protozoans in drinking water samples in the northern part of Portugal and the risk of human infection, we have established a long term program aiming at pinpointing the sources of surface water, drinking water, and environmental contamination, working with the water-supply industry. Total 43 sources of drinking water samples were selected, and a total of 167 samples were analyzed using the Method 1623. Sensitivity assays regarding the genetic characterization by PCR and sequencing of the genes, 18S SSU rRNA, for Cryptosporidium spp. and β,-giardin for G. duodenalis were set in the laboratory. According to the defined criteria, molecular analysis was performed over 4 samples. Environmental stages of the protozoa were detected in 25.7% (43 out of 167) of the water samples, 8.4% (14 out of 167) with cysts of Giardia, 10.2% (17 out of 167) with oocysts of Cryptosporidium and 7.2% (12 out of 167) for both species. The mean concentrations were 0.1-12.7 oocysts of Cryptosporidium spp. per 10 L and 0.1-108.3 cysts of Giardia duodenalis per 10 L. Our results suggest that the efficiency in drinking water plants must be ameliorated in their efficiency in reducing the levels of contamination. We suggest the implementation of systematic monitoring programs for both protozoa. To authors'' knowledge, this is the first report evaluating the concentration of environmental stages of Cryptosporidium and Giardia in drinking water samples in the northern part of Portugal.     

Metal ion interaction with a novel anthracene pendant-armed fluorescent molecular probe. Synthesis, characterization, and fluorescence studies

A new scorpionate system (L) containing an emissive anthracene pendant arm, derived of O¹,O⁷-bis(2-formylphenyl)-1,4,7-trioxaheptane and tren, has been synthesized and characterized. The sensing capability of L towards a range of metal ions has been studied. Protonation and complexation studies, using UV-Vis and fluorescent emission measurements, have been performed with alkaline and alkaline earth metal ions (M = Na(I), K(I), Li(I), Ca(II), Mg(II)), as well as transition and post-transition metal ions (M = Cr(III), Cu(II) and Zn(II), Cd(II), Hg(II) and Al(III)). An increase in the fluorescence emission (CHEF effect) was observed in methanol and in methanol/water mixtures in the presence of Cd(II) (5.0-fold), Zn(II) (4.5-fold), Cr(III) (2.0-fold) and Al(III) (1.8-fold); these results suggest a notable sensing ability of this new N₃O₄ ligand for these metals; these experiments were also performed in the presence of large amounts of alkaline and alkaline earth metal ions.     

Effects of 20-HETE on Na+ transport and Na+ -K+ -ATPase activity in the thick ascending loop of Henle

Previous studies have indicated that 20-hydroxyeicosatetraenoic acid (20-HETE) inhibits Na+ transport in the medullary thick ascending loop of Henle (mTALH), but the mechanisms involved remain uncertain. The present study compared the effects of 20-HETE with those of ouabain and furosemide on intracellular Na+ concentration ([Na+]i), Na+ -K+ -ATPase activity, and 86Rb+ uptake, an index of Na+ transport, in mTALH isolated from rats. Ouabain (2 mM) increased, whereas furosemide (100 microM) decreased, [Na+]i in the mTALH of rats. Ouabain and furosemide inhibited 86Rb+ uptake by 91 and 30%, respectively. 20-HETE (1 microM) had a similar effect as ouabain and increased [Na+]i from 19 +/- 1 to 30 +/- 1 mM. 20-HETE reduced Na+ -K+ -ATPase activity by 30% and 86Rb+ uptake by 37%, but it had no effect on 86Rb+ uptake or [Na+]i in the mTALH of rats pretreated with ouabain. 20-HETE inhibited 86Rb+ uptake by 12% and increased [Na+]i by 19 mM in mTALH pretreated with furosemide. These findings indicate that 20-HETE secondarily inhibits Na+ transport in the mTALH of the rat, at least, in part by inhibiting the Na+ -K+ -ATPase activity and raising [Na+]i.     

Omega-alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: a study of chain-length and stereochemical dependence

A series of omega-alkoxy ethers were prepared with variation of the length of the aliphatic chain of suberoylanilide hydroxamic acid (SAHA, vorinostat). Eight carbon long chain analogues showed the best activity, among which several substituted benzyl ether derivatives exhibited inhibitory activity on HDAC comparable to SAHA, and antiproliferative activity on three human cell lines (NB4, H460, and HCT-116) better than SAHA. However, no significant difference in antiproliferative activity was observed between two enantiomers bearing the benzyl ether moiety.