Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

Risk groups in bladder cancer patients treated with radical cystectomy

Objective To stratify patients with bladder cancer into homogeneous risk groups according to statistically significant differences found in PFS (progression-free survival). To identify those patients at increased risk of progression and to provide oncological follow-up according to patient risk group. Materials and Methods A retrospective study of 563 patients treated with radical cystectomy (RC). In order to determine which factors might predict bladder tumour progression and death, uni- and multivariate analyses were performed. The risk groups were identified according to “inter-category” differences found in PFS and lack of differences, thus revealing intra-category homogeneity. Results Median follow up time was 37.8 months. Recurrence occurred in a total of 219 patients (38, 9%). In 63% of cases this was distant recurrence. Only two variables retained independent prognostic value in the multivariate analysis for PFS: pathological organ confinement and lymph node involvement. By combining these two variables, we created a new “risk group” variable. In this second model it was found that the new variable behaved as an independent predictor associated with PFS. Four risk groups were identified: very low, low, intermediate and high risk: • Very low risk: pT0 N0 • Low risk: pTa, pTis, pT1, pT2 and pN0 • Intermediate risk: pT3 and pN0 • High risk: pT4 N0 or pN1-3. Conclusions We retrospectively identified 4 risk groups with an independent prognostic value for progression-free survival following RC. Differences in recurrence patterns after RC between risk groups have led us to set different intervals in monitoring for cancer. .

Risk behaviour and noise exposure among adolescents.

Adolescents in Western society often expose themselves to high levels of sound in gyms, rock concerts, discotheques etc. As these behaviours are as threatening to young people's health as more traditional risk behaviours are, our aim in the present study was to analyze the relationship between self-exposure to noise, risk behaviours and risk judgements among 310 Swedish adolescents aged 15-20 (167 men; 143 women). Adolescents' behaviour in different traditional risk situations correlated with behaviour in noisy environments, while judgements about traditional risks correlated with judgements regarding noise exposure. It is an interesting finding that although young women judge risk situations as generally more dangerous than young men do, they nevertheless behave in the same way. We suggest that this difference is a social and cultural phenomenon which underscores the importance of adopting a gender perspective in the analysis of risk factors. Adolescents reporting permanent tinnitus judged loud music as more risky than adolescents with no symptoms and they did not listen to loud music as often as those with occasional tinnitus. Research on hearing prevention for young people needs to acknowledge and make use of theories on risk behaviour, especially due to the existence of a relationship between adolescents' risk-taking in noisy environments and other types of risk-taking. Similarly, theories on risk behaviour should acknowledge noise as a risk factor.

Age-related hearing loss and blood pressure.

A review of the literature studying possible correlations between hearing function and cardiovascular disease (CVD) reveals a complex and somewhat contradictory picture. Most studies favor the concept of an association between hearing loss and CVD. The issue of interactions between noise-induced hearing loss and CVD, as well as between age-related hearing loss and CVD, has been discussed in numerous publications. The present study utilizes information from an epidemiological study of elderly people in Gothenburg, Sweden. We found a probable correlation between high systolic blood pressure and hearing loss in the low and mid frequencies in elderly women, 79 years old. A tendency of a similar correlation was also found in a group of 85-year-old women. An association between high diastolic blood pressure and low- and mid-frequency hearing loss was also found in the group of women aged 85 years. No consistent associations between blood pressure or hypertension and auditory function were found in 70- and 75-year-old women or in men 70 to 85 years old.

Hearing loss in young men: possible aetiological factors.

In the present retrospective register study a very large data base consisting of screening audiograms obtained at military conscription of 18-year-old Swedish men was used. The study group comprised 450,175 men, aged 18 years, tested at conscription to military service. There were nine age groups covering a 24-year period, from 1971 to 1995. This database was compared with a number of different pre- and postnatal factors with possible influence on the hearing function. This ecologic methodology gives tentative clues (but no proof) of possible ototraumatic influences. The hearing capacity was fairly similar during the entire span of the study and only small variations were observed. There was a slight tendency of better hearing capacity in the later age groups, compared with the earlier ones. The mean thresholds of the frequencies 4 and 6 kHz were slightly elevated in 1971, 1976 and, to some extent also in 1992. We tried to calculate the levels of leisure noise exposure during the study period. There was no apparent tendency of reduced noise levels, on the contrary the noise levels seemed to increase. The treatment programmes for acute otitis media (AOM) underwent considerable changes during the period from the early fifties to the early eighties, when the participants were pre-school children. One possible explanation for the slight improvement of the hearing capacity could be less ototraumatic influence of AOM. Data about the occurrence of four common epidemic diseases, covering the periods preceding and succeeding the years when the participants were born indicated that influenza and possibly pertussis (whooping cough), constitute putative prenatal risk factors for mild to moderate high frequency hearing loss.

Audiological findings in workers exposed to styrene alone or in concert with noise.

Audiological testing, interviews and exposure measurements were used to collect data on the health effects of styrene exposures in 313 workers from fiberglass and metal-product manufacturing plants and a mail terminal. The audiological test battery included pure-tone audiometry, distortion product otoacoustic emissions (DPOAE), psychoacoustic modulation transfer function, interrupted speech, speech recognition in noise and cortical response audiometry (CRA). Workers exposed to noise and styrene had significantly poorer pure-tone thresholds in the high-frequency range (3 to 8 kHz) than the controls, noise-exposed workers and those listed in a Swedish age-specific database. Even though abnormalities were noted on DPOAE and CRA testing, the interrupted speech and speech recognition in noise tests were the more sensitive tests for styrene effects. Further research is needed on the underlying mechanisms to understand the effects of styrene and on audiological test batteries to detect changes in populations exposed to solvents.

Self-reported tinnitus and noise sensitivity among adolescents in Sweden.

It seems to be a common opinion among researchers within the field of audiology that the prevalence of tinnitus will increase as a consequence of environmental factors, for example exposure to loud noise. Young people are exposed to loud sounds, more than any other age group, especially during leisure time activities, i.e. at pop concerts, discotheques and gyms. A crucial factor for the prevention of hearing impairments and hearing-related symptoms in the young population is the use of hearing protection. The focus of the present study is use of hearing protection and self-reported hearing-related symptoms, such as tinnitus and noise sensitivity in a young population of high-school students (N=1285), aged 13 to 19 years. The results show that the prevalence of permanent tinnitus and noise sensitivity, reported in the total group, was 8.7% and 17.1% respectively. Permanent tinnitus was not significantly related to level of socio-economic status, but age-related differences in the prevalence rates of experienced tinnitus and noise sensitivity were found to be significant. Older students reported such symptoms to a greater extent than younger students did. Those who reported tinnitus and other hearing-related symptoms protected their hearing to the highest extent and were the ones most worried.

Reference data for evaluation of occupationally noise-induced hearing loss.

Relevant reference data are required in order to determine the effect from occupational noise exposure on hearing. Pure-tone averages (PTA) of hearing threshold levels simplify the evaluation for audiometric frequencies typically affected by noise. The present study provides reference data of high frequency (HF) PTA over 3, 4 and 6 kHz for a general adult population, aged from 20 to 79 years, not exposed to hazardous occupational noise. The results are presented as statistical distributions of HF PTA values as functions of age, and as prevalence of different degree of HF PTA in the age groups 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years.

Road traffic noise and annoyance--an increasing environmental health problem.

Traffic noise, which is steadily increasing, is considered to be an important environmental health problem. The aim of this study was to estimate the degree of annoyance and sleep disturbance related to road traffic noise in residential settings in an urban community. The study is based on a questionnaire on environmentally related health effects distributed to a stratified random sample of 1000 individuals, 19-80 years old, in a municipality with heavy traffic in the county of Stockholm. The response rate was 76%. The individual noise exposure was estimated using evaluated noise dispersion models and local noise assessments. Frequent annoyance was reported by 13% of subjects exposed to Leq 24 hr >50 dBA compared to 2% among those exposed to <50 dBA, resulting in a difference of 11% (95% Confidence Interval (CI) 7%, 15%). Sometimes or frequently occurring sleep disturbance was reported by 23% at Leq 24 hr >50 dBA and by 13% at levels <50 dBA, a difference of 11% (95% CI 4%, 18%). A positive exposure- response relation was indicated for annoyance as well as for sleep disturbances when classifying the individuals into four different exposure categories (< 45, 46- 50, 51-55 and >55 dBA Leq 24 hr). There was some habituation to noise for problems related to sleep but not for annoyance. The prevalence of both annoyance and sleep problems was higher when bedroom windows were facing streets. People living in apartments had more sleep problems compared to people living in detached or semi-detached houses. In conclusion traffic noise exposure, even at low levels, was associated with annoyance and sleep disturbance. Access to a quiet side seemed to be a major protective factor for noise related problems.

The influence of ageing on noise-induced hearing loss.

A lifetime of exposure to noise is likely to have negative effects on the hearing, but the interaction between noise-induced hearing loss (NIHL) and age-related hearing loss is difficult to determine. The most commonly accepted assumption is a simple accumulating effects of noise and ageing on the hearing. However, both a less than additive effect as well as a supraadditive effect has been proposed. Recently an interesting interaction between NIHL and age-related hearing loss has been reported (Gates et al., 2000). NIHL before old age reduces the effects of ageing at noise-associated frequencies, but accelerates the deterioration of hearing in adjacent frequencies. Findings from the longitudinal and cross-sectional gerontological and geriatric population study of 70-year-olds in Gothenburg, Sweden supports these observations. The incidence of tinnitus increases in old age, but not at the same high rate as presbyacusis. According to the gerontological and geriatric population study in Gothenburg tinnitus in old age is related more to hearing loss than to ageing. There are no simple correlations between exposure to noise during the active years and tinnitus in old age.

Occurrence of plasmids in A. actinomycetemcomitans isolated in different countries / Ocorrência de plasmídios em A. actinomycetemcomitans provenientes de diferentes países

A ocorrência de plasmídios em cepas de A. actinomycetemcomitans apresenta resultados contraditórios. O objetivo do presente estudo foi o de detectar a ocorrência de elementos extracromossômicos em amostras de bactérias provenientes de diferentes países. Foram analisadas 57 cepas isoladas no Brasil, na Suécia, no Quênia e no Japäo, além de amostras de referência. Entre as cepas analisadas, 15 apresentaram plasmídios, através do método de BIRBOIM; DOLY, sendo 14 isoladas no Brasil e uma, na Suécia. As amostras isoladas no Japäo e no Quênia näo apresentaram plasmídios. Esses resultados demonstraram uma possível variabilidade na ocorrência de plasmídios detectáveis entre amostras provenientes de diferentes países