Does pregnancy-induced hypertension affect the electrophysiology of the heart?

Pregnancy-induced hypertension (PIHT) increases both maternal and neonatal mortality and morbidity in pregnant women. We sought to investigate the electrocardiographic findings in pregnant women with PIHT. Seventeen pregnant women (29.4 ± 5 years) with PIHT and 24 pregnant women (27.3 ± 6.1 years) with normal blood pressure (control group) were included in the study. A 12-lead surface electrocardiogram was used to evaluate the electrocardiographic parameters. Pregnant women with PIHT had higher blood pressure (p = 0.001). The Tp-e interval was longer in PIHT pregnant women at 83.5 ± 7.8 ms versus 75.8 ± 8.4 ms in the control group (p = 0.007). The Tp-e/QTc ratio was higher in pregnant women with PIHT than that in healthy controls (0.19 ± 0.02 vs. 0.18 ± 0.02, respectively). This study demonstrated that Pd, QTd and the P wave durations were similar in the PIHT pregnant women and control group, but the Tp-e and Tp-e/QTc ratio were higher in pregnant women with PIHT than in normotensive pregnant women.

Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and carotid intima-media thickness: Associations in rheumatoid arthritis patients.

AIM: The purpose of this work was to evaluate epicardial adipose tissue (EAT), carotid intima-media thickness (CIMT), and flow-mediated dilatation (FMD) of the brachial artery in rheumatoid arthritis (RA) patients using ultrasonographic methods. Interrelationships between these three parameters in RA patients were also investigated. METHODS: EAT thickness, CIMT, and FMD were measured by ultrasonography. We measured the disease activity score (DAS28), health assessment questionnaire (HAQ) score, and C-reactive protein (CRP) levels. Spearman or Pearson correlation analysis was used to evaluate the association between clinical findings, CIMT, FMD, and EAT. RESULTS: A total of 90 RA patients [19 men, mean age 54 years (range 21-76 years)] and 59 age- and gender-matched control subjects [17 men, mean age 54 years (range 26-80 years)] were included in the study. Patients with RA had a mean 4.34 DAS28 points (range 0-40 points) and the mean duration of the disease was 77.1 months (range 1-360 months). We found that RA patients had thicker EAT (7.7 ± 1.7 mm vs 6.2 ± 1.8 mm, p < 0.001), increased CIMT [0.9 (0.5-1.2) mm vs 0.6 (0.4-0.9) mm, p < 0.001], and decreased FMD values [5.7 % (- 23.5 to 20 %) vs. 8.5 % (- 4.7 to 22.2 %), p = 0.028] when compared to control subjects. CRP levels were significantly higher in the RA group [0.81 (range 0.1-13.5) vs 0.22 (range 0.05-12), p < 0.001]. EAT thickness was negatively correlated with FMD (r = - 0.26, p < 0.001) and positively correlated with CIMT values (r = 0.52, p < 0.001). CIMT also negatively correlated with FMD (r = - 0.29, p < 0.001). CONCLUSION: EAT can be simply measured by echocardiography and correlated with FMD and CIMT. It can be used as a first-line measurement for estimating burden of atherosclerosis in RA patients.

Effect of hypertension on echocardiographic parameters in rheumatoid arthritis.

OBJECTIVE: Hypertension (HTN) is common in rheumatoid arthritis (RA) patients. Both HTN and RA have a negative impact on echocardiographically determined parameters including wall thickness, chamber diameter, diastolic function, epicardial adipose tissue (EAT) and carotid intima media thickness (CIMT). We aimed to demonstrate the effect of HTN on these parameters in RA patients. METHODS: Patients were divided into two groups: one group comprised 39 RA patients with HTN (7 male, mean age 56.3 ± 8.4 years) and the second comprised 38 age- and gender-matched RA patients without HTN (10 male, mean age 55.3 ± 7.4 years). We retrospectively analyzed the RA patients without overt structural heart disease by determining the study parameters from echocardiograph recordings. The two groups were compared in terms of echocardiographic parameters and disease characteristics. RESULTS: RA characteristics, chamber sizes and wall thicknesses did not differ between the groups. CIMT was significantly increased in the RA with HTN group (median 0.9 mm, range 0.6-1.2 mm vs. median 0.8 mm, range 0.6-1.0 mm; p = 0.031). EAT was also significantly increased in the RA with HTN group (8.2 ± 1.8 mm vs. 7.4 ± 1.4 mm; p = 0.022). Septal early diastolic E' wave velocities were significantly decreased in the RA with HTN group (8.8 ± 2.4 cm/s vs. 10.2 ± 1.8 cm/s; p = 0.016). CONCLUSION: HTN has a further negative impact on diastolic functions, CIMT and EAT in RA patients.

Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer.

BACKGROUND: Prostate cancer (CaP) preferentially metastasises to the bone, and we have previously shown that the poly-unsaturated fatty acid (PUFA) arachidonic acid (AA) is a potent stimulator of CaP invasion. Here we present that AA promotes CaP invasion by inducing bone marrow adipocyte formation. METHODS: Boyden invasion-chamber assays assessed the ability of dietary oils, their PUFA components, and specific PUFA-loaded adipocytes to induce PC-3 invasion. Lipid transfer and metabolism was followed using deuterated AA and Fourier Transform Infrared spectroscopy (FTIR). RESULTS: Poly-unsaturated fatty acid constituents, but not their corresponding dietary oils, induced PC-3 invasion. PUFAs induce bone marrow adipocyte (BM-Ad) differentiation with AA inducing higher levels of BM-Ad differentiation, as compared with other PUFAs (3998+/-514.4 vs 932+/-265.8; P=0.00002), which stimulated greater PC-3 invasion than free AA (22 408.5+/-607.4 vs 16 236+/-313.9; P=0.01111) or adipocytes generated in the presence of other PUFAs. In bone marrow co-culture PC-3 and BM-Ad interactions result in direct uptake and metabolism of AA by PC-3 cells, destruction of the adipocyte and subsequent formation of a bone metastasis. CONCLUSION: The data supports the hypothesis that AA not only promotes CaP invasion, it also prepares the 'soil', making it more supportive for implantation and propagation of the migrating metastatic cell.

Factors influencing the discrimination and classification of prostate cancer cell lines by FTIR microspectroscopy.

In this study we obtained Fourier transform infrared (FTIR) spectra of fixed prostate cell lines of differing types as well as the primary epithelial cells from benign prostatic hyperplasia (BPH). Results showed that by using multivariate chemometric analysis it was possible to discriminate and classify these cell lines, which gave rise to sensitivity and specificity values of >94% and >98%, respectively. Following on from these results the possible influences of different factors on the discrimination and classification of the prostate cell lines were examined. Firstly, the effect of using different growth media during cell culturing was investigated, with results indicating that this did not influence chemometric discrimination. Secondly, differences in the nucleus-to-cytoplasm (N/C) ratio were examined, and it was concluded that this factor was not the main reason for the discrimination and classification of the prostate cancer (CaP) cell lines. In conclusion, given the fact that neither growth media nor N/C ratio could totally explain the classification it is likely that actual biochemical differences between the cell lines is the major contributing factor.

FTIR-based spectroscopic analysis in the identification of clinically aggressive prostate cancer.

Fourier transform infrared (FTIR) spectroscopy is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds within the sample that absorbs it. As different samples contain different molecular bonds or different configurations of molecular bonds, FTIR allows us to obtain chemical information on molecules within the sample. Fourier transform infrared microspectroscopy in conjunction with a principal component-discriminant function analysis (PC-DFA) algorithm was applied to the grading of prostate cancer (CaP) tissue specimens. The PC-DFA algorithm is used alongside the established diagnostic measures of Gleason grading and the tumour/node/metastasis system. Principal component-discriminant function analysis improved the sensitivity and specificity of a three-band Gleason score criterion diagnosis previously reported by attaining an overall sensitivity of 92.3% and specificity of 99.4%. For the first time, we present the use of a two-band criterion showing an association of FTIR-based spectral characteristics with clinically aggressive behaviour in CaP manifest as local and/or distal spread. This paper shows the potential for the use of spectroscopic analysis for the evaluation of the biopotential of CaP in an accurate and reproducible manner.

Biomolecular profiling of metastatic prostate cancer cells in bone marrow tissue using FTIR microspectroscopy: a pilot study.

Prostate cancer (CaP) cells preferentially metastasise to the bone marrow, a microenvironment that plays a substantial role in the sustenance and progression of the CaP tumour. Here we use a combination of FTIR microspectroscopy and histological stains to increase molecular specificity and probe the biochemistry of metastatic CaP cells in bone marrow tissue derived from a limited source of paraffin-embedded biopsies of different patients. This provides distinction between the following dominant metabolic processes driving the proliferation of the metastatic cells in each of these biopsies: glycerophospholipid synthesis from triacylglyceride, available from surrounding adipocytes, in specimen 1, through significantly high (p < or = 0.05) carbohydrate (8.23 +/- 1.44 cm(-1)), phosphate (6.13 +/- 1.5 cm(-1)) and lipid hydrocarbon (24.14 +/- 5.9 cm(-1)) signals compared with the organ-confined CaP control (OC CaP), together with vacuolation of cell cytoplasm; glycolipid synthesis in specimen 2, through significantly high (p < or = 0.05) carbohydrate (5.51 +/- 0.04 cm(-1)) and high lipid hydrocarbon (17.91 +/- 2.3 cm(-1)) compared with OC CaP, together with positive diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells; glycolysis in specimen 3, though significantly high (p < or = 0.05) carbohydrate (8.86 +/- 1.78 cm(-1)) and significantly lower (p < or = 0.05) lipid hydrocarbon (11.67 +/- 0.4 cm(-1)) than OC CaP, together with negative diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells. Detailed understanding of the biochemistry underpinning the proliferation of tumour cells at metastatic sites may help towards refining chemotherapeutic treatment.

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs.

Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations

Fixation protocols for subcellular imaging by synchrotron-based Fourier transform infrared microspectroscopy.

Synchrotron-based Fourier transform infrared (SR-FTIR) microspectroscopy is a powerful bioanalytical technique for the simultaneous analysis of lipids, proteins, carbohydrates, and a variety of phosphorylated molecules within intact cells. SR-FTIR microspectroscopy can be used in the imaging mode to generate biospectroscopic maps of the distribution and intensity profiles of subcellular biomolecular domains at diffraction-limited spatial resolution. However, the acquisition of highly spatially resolved IR images of cells is not only a function of instrumental parameters (source brightness, sampling aperture size) but also the cell preparation method employed. Additionally, for the IR data to be biochemically relevant the cells must be preserved in a life-like state without introducing artefacts. In the present study we demonstrate, for the first time, the differences in biomolecular localizations observed in SR-FTIR images of cells fixed by formalin, formalin-critical point drying (CPD), and glutaraldehyde-osmium tetroxide-CPD, using the PC-3 prostate cancer cell line. We compare these SR-FTIR images of fixed cells to unfixed cells. The influence of chemical fixatives on the IR spectrum is discussed in addition to the biological significance of the observed localizations. Our experiments reveal that formalin fixation at low concentration preserves lipid, phosphate, and protein components without significantly influencing the IR spectrum of the cell.

Paralytic complications of puffer fish (tetrodotoxin) poisoning.

INTRODUCTION: Puffer fish is available in Bangladesh and is occasionally eaten by some people. Ignorance regarding its proper cooking process may lead to serious health hazards, including fatality. METHODS: An unusual catastrophic event happened recently in Khulna, Bangladesh that drew nationwide attention. Eight families were affected. RESULTS: Thirty-seven patients were admitted with a history of consumption of puffer fish. Peri-oral paraesthesia (24), weakness of both lower limbs (22), paraesthesia all over the body (18), headache (15), difficulty in respiration (14), nausea and vomiting (8), blurring of vision (7), and vertigo (6) were common clinical presentations. Twenty-two patients developed ascending paralysis of limbs and involved the respiratory muscles in 17 patients. Eight patients died due to respiratory failure while the rest improved. CONCLUSION: Health personnel should have sufficient knowledge regarding the clinical manifestations, complications and management of puffer fish poisoning. During its preparation, organs that contain the highest level of tetrodotoxin should be removed. Since there is no specific treatment, people should be made aware of the potential risk of eating puffer fish, about the warning symptoms and signs of puffer fish poisoning, and when to seek medical help.

Applications of Fourier transform infrared microspectroscopy in studies of benign prostate and prostate cancer. A pilot study.

Fourier transform infrared (FTIR) microspectroscopy has been applied to a study of prostate cancer cell lines derived from different metastatic sites and to tissue from benign prostate and Gleason-graded malignant prostate tissue. Paraffin-embedded tissue samples were analysed by FTIR, after mounting onto a BaF(2) plate and subsequent removal of wax using Citroclear followed by acetone. Cell lines were analysed as aliquots of cell suspension held between two BaF(2) plates. It was found that the ratio of peak areas at 1030 and 1080 cm(-1), corresponding to the glycogen and phosphate vibrations respectively, suggests a potential method for the differentiation of benign from malignant cells. The use of this ratio in association with FTIR spectral imaging provides a basis for estimating areas of malignant tissue within defined regions of a specimen. Initial chemometric treatment of FTIR spectra, using the linear discriminant algorithm, demonstrates a promising method for the classification of benign and malignant tissue and the separation of Gleason-graded CaP spectra. Using the principle component analysis, this study has achieved for the first time the separation of FTIR spectra of prostate cancer cell lines derived from different metastatic sites.

Transplacental and lactational transfer of p,p'-DDE in Sprague-Dawley rats.

p,p'-DDE (hereafter DDE), a persistent metabolite of p,p'-DDT, is a widespread environmental contaminant that can induce antiandrogenic developmental effects in rats. Quantitative measurements of the transfer of DDE from pregnant or lactating dams to the fetus or suckling neonate were performed, and physiologically based pharmacokinetic (PBPK) models for the transplacental and lactational transfer of DDE were developed. Pregnant Sprague-Dawley rats were dosed by gavage in corn oil with either 10 or 100 mg DDE per kg body wt per day from Gestation Day (gd) 14 to 18. DDE was analyzed in several maternal tissues as well as in fetal and neonatal tissues from gd 15 to Postnatal Day (pnd) 21. Fetal DDE concentrations were about threefold lower than corresponding placental concentrations. By adopting a cross-fostering design, the contributions of transplacental and lactational transfer were compared. In the pup liver, where DDE was detectable in the 100 mg/kg groups on pnd 10, the lactationally exposed group had DDE concentrations about 50 times higher than those of the in utero only exposure group; the lactation only exposure groups had DDE tissue dose profiles very similar to those of the in utero plus lactation exposure groups, indicating that the lactational route is far more important than the in utero route quantitatively. The PBPK models postulated initial absorption of DDE into both the blood circulation and lymphatic system with the primary storage sites being maternal and neonatal adipose tissues. Mobilization of DDE from its storage sites is postulated to occur via its association with mobilized fatty acids and lipoproteins. The results provide an overall framework for evaluating the tissue dosimetry of DDE and for understanding how maternal exposure to DDE could affect perinatal sexual development in utero or in the early postnatal period.