In case of obesity,longevity-related mechanisms lead to anti-inflammation

The exact mechanisms which contribute to longevity have not been figured out yet. Our aim was to find out a common way for prompting longevity by bringing together the well-known applications such as food restriction, exercise, and probiotic supplementing in an experimental obesity model. Experimental obesity was promoted in a total of 32 young (2 months old) and 32 aged (16 months old) male Wistar albino rats through 8-week cafeteria diet (salami, chocolate, chips, and biscuits). Old and young animals were divided into groups each consisting of eight animals and also divided into four subgroups as obese control, obese food restriction, obese probiotic-fed and obese exercise groups. Probiotic group diet contained 0.05 %w/total diet inactive and lyophilized Lactobacillus casei str. Shirota. The exercise group was subjected to treadmill running 1 h/day, at 21 m/min and at an uphill incline of 15 % for 5 days a week. Food restriction group was formed by giving 40 % less food than the others. The control group was fed regular pellet feed ad libitum. This program was continued for 16 weeks. Blood samples from all the groups were analyzed for fasting glucose, insulin, IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3), interleukin (IL)-6, IL-12, malondialdehyde (MDA), fT3, TT3, fT4, TT4, and liver tissue MDA levels were measured. All applications showed anti-inflammatory effects through the observed changes in the levels of IGFBP-3, IL-6, and IL-12 in the young and old obese rats. While the interventions normally contribute to longevity by recruiting different action mechanisms, anti-inflammatory effect is the only mode of action for all the applications in the obesity model.     

A novel recombinant soluble splice variant of Met is a potent antagonist of the hepatocyte growth factor/scatter factor-Met pathway

PURPOSE: The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), are involved in a wide range of biological activities, including cell proliferation, motility, invasion, and angiogenesis. The HGF/SF-Met signaling pathway is frequently activated in a variety of cancers, and uncontrolled Met activation correlates with highly invasive tumors and poor prognosis. In this study, we investigated the inhibitory effect of a novel soluble splice variant of Met on the HGF/SF-Met pathway. EXPERIMENTAL DESIGN: Using our alternative splicing modeling platform LEADS, we have identified a novel splice variant of the Met receptor, which encodes a truncated soluble form of the receptor. This variant was produced as a recombinant Fc-fused protein named Cgen-241A and was tested in various cell-based assays representing different outcomes of the HGF/SF-Met pathway. RESULTS: Cgen-241A significantly inhibited HGF/SF-induced Met phosphorylation as well as cell proliferation and survival. In addition, Cgen-241A showed a profound inhibitory effect on cell scattering, invasion, and urokinase up-regulation. The inhibitory effects of Cgen-241A were shown in multiple human and nonhuman cell types, representing different modes of Met activation. Furthermore, Cgen-241A showed direct binding to HGF/SF. CONCLUSIONS: Taken together, our results indicate that Cgen-241A is a potent antagonist of the HGF/SF-Met pathway, underlining its potential as a therapeutic agent for the treatment of a wide variety of human malignancies that are dependent on this pathway.     

High risk of pleural mesothelioma among the state railroad carriage repair workers

Exposure to asbestos in a facility for the repair of railroad carriages in Bologna was initially studied in 1980, when the Local Health Unit started a program of primary prevention on request of the Unions. At that time workers employed in jobs with high exposure to asbestos were identified. The mortality experience of these 173 subjects was investigated from 01.01.1979 through 31.12.1997, and compared to that of the population of Emilia Romagna. SMR for all causes was 69, with upper limit of the confidence interval lower than 100; this was largely due to a significant decrease of cardiovascular mortality. Among neoplasms, there was a significant excess of pleural mesothelioma (6 observed, 0.09 expected); one more subject died for peritoneal mesothelioma and one for malignant mesothelioma of unspecified site. About half of the subjects deceased for neoplastic disease (8/17) were affected by mesothelioma.     

Cohort study of mortality among leather tanners in the Lower Valdarno area

BACKGROUND: Epidemiological studies of tanners have shown increased risk for a number of cancer sites, namely: lung, bladder, kidney and urinary organs as well as stomach, intestine, pancreas, nose and nasal cavities, together with leukemias and soft tissue sarcomas. OBJECTIVE: To study cause specific mortality of leather tanners in Tuscany (Valdarno Inferiore area). METHODS: The cohort included 4874 workers (4150 males and 724 females) employed in 92 tanneries operating in 1996 (Valdarno Inferiore Tanneries Census) which were also operating on 31-12-1970. Ascertainment of vital status was completed for all individuals on 31-12-1998 (end of follow-up), and the cause of death was known for all deceased subjects. Demographic and work history data were obtained from factory payrolls. Regional mortality rates were used for comparison to calculate SMR (Standardised Mortality Ratio) and 90% Confidence Intervals (CI). In addition to the overall cohort analysis, for men only separate analyses were completed for finishers, chrome tanners and vegetable tanners. RESULTS: The study showed an increased mortality from lung cancer among finishers, Standardised Mortality Ratio (SMR) 145, 19 observed (obs) (90% Confidence Intervals, 90% CI 95-212), from bladder cancer in the overall cohort (SMR 134, 9 obs, 90% CI 70-233) and among finishers (SMR 125, 2 obs, 90% CI 22-393) and from pancreatic cancer among finishers (SMR 120, 2 obs, 90% CI 21-379). Mortality from lymphoemopoietic cancer is above expected, and the increase is mainly due to myeloid leukaemia, both in males (SMR 208, 5 obs, 90% CI 82-437) and females (SMR 599, 2 obs, 90% CI 106-1887). No deaths from soft tissue sarcoma were observed. A new finding of the study was the increased mortality from cancer of the endocrine glands (SMR 566, 4 obs, 90% CI 194-1297), psychiatric disorders (SMR 195, 6 obs, 90% CI 85-385) and blood diseases (SMR 329, 4 obs, IC 90% 112-752). CONCLUSIONS: The observations of increased lung cancer mortality among finishers, of bladder cancer in the overall cohort and among finishers, as well as an increase in pancreatic cancer among the latter, confirm previous epidemiological findings among tanners. The increase in myeloid leukemia mortality for both males and females, and the absence of deaths from cancer of the connective tissue, which includes soft tissue sarcomas, are worthy of note. The results should be valued with caution, given the small number of cases and the novelty of some observations.     

The predictive nature of uterocervical angles in the termination of second trimester pregnancy

Aim: To establish how useful and the predictive capacity of uterocervical angles (UCA) in the termination of second trimester pregnancies.

Material and methods: This prospective cohort study was conducted at a tertiary center with a total of 120 singleton pregnancies delivered between 14 and 24 gestational weeks. Before the beginning of misoprostol induction, patients were screened for both cervical length (CL) and uterocervical angles (UCA). The UCA is defined as an angle constructed by the measurement of the cervical canal and lower uterine segment. The study population was subdivided into four groups; successful and failed terminations at the end of 24?hours of induction and successful and failed terminations at the end of 48?hours of induction. We decided to further evaluate our study population based on their UCAs, and placed them into four categories; UCA ≥95°, UCA <95°, UCA ≥105°, and UCA <105°.

Results: In the 24-hour time frame group, the mean UCA was 105.50?±?15.38 degrees in the successful termination group and was 100.22?±?11.12 degrees in the failed group (p?=?.001). In the 48-hour time frame group, the mean UCA was 104.19?±?13.51° in the successful termination group and was 93.52?±?7.84° in the failed group (p?=?.007). The mean hour of induction was shortest in the UCA ≥105° group.

Conclusions: Regardless of the time frames, patients who had successful terminations had a broader angle, less amount of misoprostol use and shorter duration of induction as compared to the failed termination groups. What do the results of this study add? The uterocervical angle has never been measured in second trimester pregnancies to predict the timing of termination. Our study demonstrated the useful application of this ultrasonographic finding in the prediction of successful second trimester terminations.

Trial registration: ClinicalTrials.gov identifier: NCT03220607.     

Oxygen tension-associated changes on secondary immune response in halothane or isoflurane anesthetized mice

The impact that reexposure to anesthetics delivered in 100% oxygen or in synthetic air (21% oxygen/79% nitrogen) has on the secondary humoral immune response to sheep red blood cells was studied. Mice were immunized twice with a 15-day interval and anesthetized immediately after each antigenic challenge with 1.5% halothane or 1.5% isoflurane for 40 min. Halothane in oxygen resulted in increased numbers of IgG-secreting cells (IgG-SC), while halothane in air depressed the response when compared to control mice. In contrast, isoflurane vaporized in oxygen did not affect IgG-SC numbers, while isoflurane given in air lowered the response. Furthermore, neither 100% oxygen, nor the stress of being in an anesthesia chamber breathing synthetic air for 40 min had any immunological effect in non-anesthetized mice.
The inspired oxygen concentration during halothane or isoflurane anesthesia has an effect on the secondary immune response. The effect is different between halothane and isoflurane, possibly due to differences in the extent of their metabolic and pharmacodynamic properties.