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Objectives: Air pollution and traffic noise are detrimental to cardiovascular health. However, the effects of different sources of these exposures on cardiovascular biomarkers remain unclear. We explored the associations of long-term exposure to source-specific air pollution (vehicular exhausts and residential woodsmoke) at low concentrations and road-traffic noise with systemic inflammation and cardiovascular disease biomarkers., Material and Methods: Modeled outdoor exposure to fine particulate matter (aerodynamic diameter ≤2.5 μm; PM 2.5 ) from vehicular exhausts and residential woodsmoke, nitrogen dioxide (NO 2 ) from road traffic, and road-traffic noise were linked to the home addresses of the participants (Finnish residents aged 25-74) in the FINRISK study 1997-2012. The participants were located in the cities of Helsinki, Vantaa, and the region of Turku, Finland. The outcomes were high-sensitivity C-reactive protein (CRP), a biomarker for systemic inflammation, and cardiovascular disease biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I. We performed cross-sectional analyses with linear and additive models and adjusted for potential confounders., Results: We found no association between PM 2.5 from vehicular exhausts (% CRP difference for 1 μg/m 3 increase in PM 2.5 : -0.9, 95% confidence interval, CI: -7.2, 5.8), or from residential woodsmoke (% difference: -8.1, 95% CI: -21.7, 7.9) and CRP (N = 4147). Road-traffic noise >70 dB tended to be positively associated with CRP (% CRP difference versus noise reference category of ≤45 dB: 18.3, 95% CI: -0.5, 40.6), but the association lacked significance and robustness (N = 7142). Otherwise, we found no association between road-traffic noise and CRP, nor between NO 2 from road traffic and NT-proBNP (N = 1907) or troponin I (N = 1951)., Conclusion: Long-term exposures to source-specific, fairly low-level air pollution from vehicular exhausts and residential woodsmoke, or road-traffic noise were not associated with systemic inflammation and cardiovascular disease biomarkers in this urban area., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tanja Zeller has patent #397 WO2022043229A1 licensed to a computing device to estimate the probability of myocardial infarction. Tanja Zeller is shareholder of the ART.EMIS GmbH Hamburg. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The multifactorial consequences of menopausal estrogen deficiency affect numerous tissues throughout the body. Supplemental hormonal therapies carry the burden of a risk/benefit ratio that must be highly individualized. Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) agonist/antagonists designed to induce benefits comparable with estrogen while minimizing adverse effects. Here, we review the estrogen agonist/antagonist profile of ospemifene, a novel triphenylethylene derivative recently approved to treat dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause, both preclinically and clinically. Ospemifene binds ERα and ERβ with approximately equal affinities. In preclinical models, ospemifene increased vaginal and uterine epithelial thickness and mucification to the same extent as estrogen. Ospemifene did not induce endometrial hyperplasia in animal models; there also was no stimulatory effect on endometrial cells. In rat and human mammary cells in vitro, ospemifene evokes a dose-dependent inhibition on estrogen-induced cell responses and cell proliferation, supporting an antiestrogenic effect in breast. In contrast, ospemifene has an estrogenic effect on bone, as seen by improved bone mineral density, strength, mass, and histomorphometry in preclinical models, consistent with improvements in markers of bone resorption and formation in postmenopausal women. Based on the preclinical evidence, ospemifene has beneficial estrogen-like effects on the vaginal epithelium, preliminary evidence to support a neutral endometrial profile, antiproliferative effects in breast, and estrogenic effects in bone. Taken together, especially regarding estrogen-like effects on the vaginal epithelium, ospemifene presents a profile of tissue-specific effects that appear novel among available SERMs and well-suited for the treatment of VVA., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: Atherosclerosis of arteries supplying the lumbar region has been suggested as a mechanism leading to intervertebral disc degeneration and sciatica. The study described here examined whether serum lipid levels or pharmacologically treated hyperlipidemia were associated with sciatica., Methods: A nationally representative sample (n=8028) of Finns aged 30 years or over was interviewed and examined. Sciatica was assessed by a physician according to preset criteria. Information for the present purpose was available for 74.8% of the sample., Results: The prevalence of sciatica was 3.3% for men and 2.2% for women. In men without hyperlipidemia treatment, sciatica was associated with total cholesterol (high vs. low tertile: OR 2.28, 95% CI 1.14-4.55), LDL cholesterol (2.12; 1.11-4.05), and triglycerides (1.92; 1.04-3.55), adjusted for age, BMI, exercise, smoking, heavy physical work, and education. HDL was not associated with sciatica. For men in the highest tertile of both total cholesterol and triglycerides, the OR of sciatica was 3.89 (1.68-8.99) in comparison to men with cholesterol in the lowest tertile and triglycerides in the lowest or the middle tertile. In similar analyses among women no associations were seen. Pharmacologically treated hyperlipidemia was associated with sciatica in women (2.02; 1.01-4.04), but not in men (1.71; 0.83-3.55)., Conclusions: Independent of BMI and other possible confounders, clinically assessed sciatica in men was associated with levels of atherogenic serum lipids. Pharmacologically treated hyperlipidemia was associated with sciatica in women. The findings are in accordance with the atherosclerosis-sciatica hypothesis.

The object of the study was to describe socioeconomic and demographic determinants of inpatient hospital care for lumbar intervertebral disc disorders (LIDD) in Finland. Information from the 1996 Finnish Hospital Discharge Register was linked with the 1995 Population Census. Poisson regression analyses were made with the total and the gainfully employed workforce aged 20-64 y as reference. All 48 public and seven private acute care general hospitals treating LIDD patients in Finland. In the workforce, 4643 patients aged 20-64 y (3692 among the gainfully employed) were admitted to the hospital due to LIDD (ICD-10: M51.1-M51.9) in 1996. About one-half were treated surgically. The duration of unemployment in 1995 was inversely associated with hospitalisation for LIDD in 1996, allowing for age, sex, education and personal income (unemployed for 12 months vs 0 months: rate ratio 0.66; 95% CI 0.57-0.77). Among those employed for 12 months in 1995, the level of education was inversely associated with the hospital admission rate. The rate was also higher in manual occupations as compared with the upper white-collar employees. The associations were clearer among the medically than the surgically treated patients. Hospitalisation for back disorder was, however, less common in the lowest income group as compared with the highest (0.65; 0.57-0.77) allowing for education, occupational class, age and sex. Women were less often admitted to the hospital than men, allowing for the socioeconomic factors (0.83; 0.77-0.90). When indicated by education or occupation, low socioeconomic status was associated with a relatively high rate of inpatient hospital care for LIDD. When indicated by personal income, the situation was the reverse. Unemployment and female gender predicted a relatively low rate of hospitalisation.

We studied the adhesion mechanism of pancreatic carcinoma using in vitro adhesion and migration assays of stable cell lines and tumors grown from these cell lines in nude mice. We also compared the results with the expression profiles of laminins and their receptors in pancreatic carcinomas to evaluate the relevance of these mechanisms in vivo. All of the cell lines preferably adhered to laminin-5, irrespective of their capability to synthesize laminin-5. Cell migration was studied in the presence of hepatocyte growth factor, as it increased the speed of migration manyfold. Herbimycin A treatment and antibodies against the beta 1 and alpha 3 integrin subunits and laminin alpha 3 chain almost entirely blocked cell migration of the BxPC-3 cell line, whereas migration was nearly unaffected by RGD peptide and only moderately inhibited by antibody against the alpha 6 integrin subunit. Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha 3 integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha 6 beta 4 integrin. Especially HGF-treated cultures showed a prominent cytoplasmic reaction for laminin-5 at the margin of the wound. Xenografted cells formed tumors that produced and deposited the same laminin chains as the in vitro cultures. Frozen sections of human pancreatic carcinomas showed reactivity for laminin chains suggestive for expression of laminin-1 and laminin-5. Both xenografted tumors and human pancreatic carcinomas also showed stromal reactivity for laminin-5. Electron microscopy of the human tumors suggested that this was due to an abundant reduplication the basement-membrane-like material around the nests of malignant cells. Our results suggest that pancreatic carcinomas synthesize and deposit laminin-5 in the basement membrane in an abnormal manner. Invading cells adhere to this newly produced basement membrane and migrate on it by using the alpha 3 beta 1 integrin receptor recognizing laminin-5.

The potential genotoxicity of dihydroabikoviromycin was assessed in bacterial and sister-chromatid exchange (SCE) test systems. Direct cytotoxicity was also assayed using bioluminescence methods to screen for differences in cell viability among different tumour cell lines following exposure to the drug. Differential killing tests with Escherichia coli WP2 and its repair-deficient derivative CM871 indicated that a functional DNA repair system was protective against the action of dihydroabikoviromycin, implying that this compound causes some form of DNA damage and is almost certainly therefore genotoxic. Dose-dependent reversion from His- to His+ with dihydroabikoviromycin was observed in the Ames test with Salmonella typhimurium TA100, but not in frameshift tester strain TA98. Dihydroabikoviromycin also induced the sfiA gene, as indicated by beta-galactosidase induction in an SOS-chromotest with E. coli PQ37 strain. A dose-related increase in SCEs by dihydroabikoviromycin was observed in CHO cells. Growth of tumour cells was also suppressed by dihydroabikoviromycin at a dose of 10 micrograms/ml.

Attempts are being made to evaluate 2-[18F]fluoro-2-deoxy-D-glucose (FDG) as a noninvasive marker of therapy response in malignant tumors. We studied rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinomas by measuring the differential absorption ratio (DAR) and the metabolites of FDG in tumor homogenates. Half the rats were treated with the antiestrogen toremifene for 14 days and half were untreated. The histology of the tumors was studied by morphometry. The animals were killed 15, 45 or 240 min after injection. Regardless of whether the rats received toremifene or not, the fractional change in tumor volume correlated better with the DAR at 15 min [r = 0.284 (untreated) and r = 0.721 (treated)] and at 240 min [r = 0.932 (untreated)], than at 45 min [r = -0.137 (untreated) and r = 0.265 (treated)]. Inverse relations were found for the fraction of unmetabolized FDG and change in tumor volume [r = 0.070 (45 min) and r = -0.872 (240 min) for untreated tumors and r = -0.963 (15 min) and r = -0.715 (45 min) for treated tumors]. The DAR and the fraction of unmetabolized FDG correlated also [r = -0.420 (15 min), r = -0.647 (45 min) and r = -0.976 (240 min) for untreated tumors, and r = -0.963 (15 min) and r = -0.213 (45 min) for treated tumors]. No significant therapy-induced morphometrical changes were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Methenamine (hexamethylenetetramine), a urinary disinfectant, was determined in human plasma and urine by gas-liquid chromatography with a short (10 m) open-bore glass capillary column (split ratio 1:20) and nitrogen-selective detector. An almost quantitative recovery (92.1%) was achieved by simple dilution of water-containing samples (0.5 ml) with acetone (4.5 ml). After centrifugation an aliquot (2 microliter) of the supernatant was injected into the gas chromatograph. Selectivity and sensitivity of the nitrogen detector allowed the quantitation of unchanged methenamine in plasma and urine up to 24 h after a single therapeutic dose of 1 g. Reproducibility of the method was 7.6 and 2.1% (C.V.) in serum and urine, respectively. The time required for the analysis of one sample was approx. 2 min. Due to the simple extraction and short analysis time it was possible to analyze the samples concurrently with sample taking. Absorption of standard tablets and an enterosoluble preparation of methenamine hippurate was compared.

Nitrazepam and its main urinary metabolites, 7-aminonitrazepam and 7-acetamidonitrazepam, free and conjugared, were determined from 24-h fractions of human urine after a single oral dose of 5 mg of nitrazepam. Nitrazepam and the metabolites were extracted before and after glusulase hydrolysis with benzene--dichloromethane (90:10) from a 1.0 ml sample. Methylnitrazepam and methylbromazepam served as internal standards. Recoveries were better than 90%. GLC analysis of nitrazepam was performed using a 63Ni electron-capture detector. The metabolites were measured by a dual flameless nitrogen selective detector. The detection limits were about 0.2 ng/ml for nitrazepam and 50 ng/ml for the metabolites. The nitrogen-selective detector responds similarly to all three compounds. The 63Ni electron-capture detector gives very poor response to 7-amino-nitrazepam but allows very sensitive detection of nitrazepam. Combined use of the two detectors gives valuable information about the metabolic profile of nitrazepam.

Sixty-one patients received nitrazepam 5 mg by mouth on the night before operation, followed by 2.5 mg given on the morning of operation and were compared with 60 patients who received no premedication. All were undergoing either therapeutic abortion, by dilatation and curettage, or explorative curettage. The plasma concentrations of nitrazepam were determined by gas chromatography and compared with the clinical effects of the drug. The premedicated patients slept better on the night before operation, and were more sedated and less apprehensive. Headache was more frequent following nitrazepam. There was no significant difference between the groups in respect of dizziness and nausea. The unpremedicated patients had a faster average heart rate. There was no obvious relationship between the plasma concentration of nitrazepam and the quality of sleep, degree of sedation, apprehension, excitement or headache.

In a double-blind randomized study 47 patients received tofizopam 100 mg orally the night before operation, and 100 mg on the morning of operation; 49 patients received nitrazepam 5 mg and 50 patients received placebo. On average the nitrazepam group slept better and were better sedated than the tofizopam or placebo groups. Compared with placebo or nitrazepam, tofizopam decreased the excitement of the patients. The effect tofizopam on apprehension and excitement was significantly better than those of placebo or nitrazepam. Nitrazepam, but not tofizopam, significantly decreased the induction requirements of thiopentone.

Nitrazepam in plasma was determined by gas-liquid chromatography with a nickel-63 electron-capture detector, unchanged by a direct method and also by a hydrolysis method. The extraction in the direct method was carried out with benzenedichloromethane (90:10) and in the hydrolysis method with diethyl ether. The hydrolysis was performed with 6 N sulphuric acid. The hydrolysis product was extracted with toluene-n-heptane-ethyl acetate (80:20:5) directly from acid. Thus the commonly used change in pH was omitted. Nitrazepam concentrations in plasma were determined in 10 healthy volunteers after two oral doses (5 and 10 mg); 0.5 ml of plasma was used for each determination and clonazepam, methylbromazepam and methylnitrazepam were used as internal standards. The recoveries of the methods are almost quantitative (greater than 96%). The two methods are clinically comparable. The high sensitivity and specificity make these methods useful in clinical determinations of nitrazepam in plasma. Advantages and disadvantages of both methods are discussed.