CETP is a determinant of serum LDL-cholesterol but not HDL-cholesterol in healthy Japanese

Cholesteryl ester transfer protein (CETP) is one of the factors that regulate plasma levels of HDL-cholesterol. To identify the factors that may regulate CETP activity, and to determine to what extent CETP is correlated with physiologic concentrations of lipoprotein, we performed an epidemiologic study in 586 healthy volunteers (317 males and 269 females, mean age 52.2 ± 10.9 years). CETP activity in these subjects was 192.96 ± 48.73 (mean ± S.D.) nmol/ml/h and distributed to a wide range (60–450 nmol/ml/h). Using multiple regression analysis, we found significant positive correlations between CETP activity and LDL-cholesterol (P < 0.03), apolipoprotein (apo) E (P < 0.005) and LCAT activity (P < 0.001). CETP activities showed significant negative correlation with apo A-I (P < 0.03). However, CETP activity showed no significant correlation either with HDL cholesterol or with apo B. One-way layout analysis of variance showed that alcohol drinking and cigarette smoking significantly reduced CETP activity, but there was no significant association between CETP activity and body mass index. Although CETP activities were significantly higher in females than in males (P < 0.001), multiple regression analysis showed no correlation between CETP activity and age in either the males or the females. Our results suggest that CETP activity regulates the concentration of apo A-I and LDL-cholesterol, and that such activity may be influenced by gender, alcohol consumption and cigarette smoking.     

Usefulness of directly observed therapy (DOT) during hospitalization as DOTS in Japanese style

Many patients with smear positive tuberculosis were hospitalized during the initial phase of chemotherapy but DOT was not applied to patients with tuberculosis in Japan. We tried randomized clinical study to evaluate the usefulness of DOT during admission. 135 culture positive TB patients were administered by DOT and 124 culture positive TB patients were self-administered during admission. There was no significant difference between 2 groups in the clinical background factors, treatment and the incidence of adverse reactions. Treatment completion rate was 94.1% in DOT group and 87.9% in non-DOT group. Default rate was significantly lower in DOT group (4.4%) than in non-DOT group (11.3%). We concluded that "DOT during admission" was useful to improve the outcome of chemotherapy for tuberculosis and it is preferable to apply DOT throughout treatment course for patients with tuberculosis in Japan.     

Behavioral intention to prevent cervical cancer and related factors among female high school students in Japan

Aim

This study aimed to examine female high school students’ behavioral intention to prevent cervical cancer and related factors.

Methods

The participants were 2158 female high school students at 16 high schools in A prefecture in the Tohoku region in Japan. A self‐administered questionnaire was carried out that was developed based on a conceptual framework comprising the Health Belief Model and Theory of Reasoned Action.

Results

The responses were obtained from 2072 students (96.0%). Of these, the answers of 2028 respondents were analyzed after excluding those participants who did not complete the behavioral intention item (effective response rate: 97.0%). A factor analysis and covariance structure analysis yielded a model with strong goodness‐of‐fit that explained the behavioral intentions based on an “Awareness of the importance and effectiveness of cervical cancer screening,” “Obstacles to cervical cancer prevention behavior,” “Subjective norms for adopting cervical cancer prevention behavior,” and “The behavior of someone close that encourages cervical cancer prevention behavior.”

Conclusion

The statistical analysis yielded a model with strong goodness‐of‐fit that explained female high school students’ behavioral intentions, which were related to four factors, including “the awareness of the importance and effectiveness of cervical cancer screening.”

     

Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation

Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3–72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids.     

Biphasic modulation by mGlu5 receptors of TRPV1-mediated intracellular calcium elevation in sensory neurons contributes to heat sensitivity

Background and Purpose

Elevation of glutamate, an excitatory amino acid, during inflammation and injury plays a crucial role in the reception and transmission of sensory information via ionotropic and metabotropic receptors. This study aimed to investigate the mechanisms underlying the biphasic effects of metabotropic glutamate mGlu₅ receptor activation on responses to noxious heat.

Experimental Approach

We assessed the effects of intraplantar quisqualate, a non-selective glutamate receptor agonist, on heat and mechanical pain behaviours in mice. In addition, the effects of quisqualate on the intracellular calcium response and on membrane currents mediated by TRPV1 channels, were examined in cultured dorsal root ganglion neurons from mice.

Key Results

Activation of mGlu₅ receptors in hind paw transiently increased, then decreased, the response to noxious heat. In sensory neurons, activation of mGlu₅ receptors potentiated TRPV1-mediated intracellular calcium elevation, while terminating activation of mGlu₅ receptors depressed it. TRPV1-induced currents were potentiated by activation of mGlu₅ receptors under voltage clamp conditions and these disappeared after washout. However, voltage-gated calcium currents were inhibited by the mGlu₅ receptor agonist, even after washout.

Conclusions and Implications

These results suggest that, in sensory neurons, mGlu₅ receptors biphasically modulate TRPV1-mediated intracellular calcium response via transient potentiation of TRPV1 channel-induced currents and persistent inhibition of voltage-gated calcium currents, contributing to heat hyper- and hypoalgesia.     

Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT

Journal of Gastroenterology - REFLECT was an open-label, phase 3 study comparing the efficacy and safety of lenvatinib versus sorafenib in patients with unresectable hepatocellular carcinoma...     

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders, formerly known as autoimmune pancreatitis (AIP), autoimmune sialadenitis, and autoimmune sclerosing cholangitis, are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease (IgG4-RD). AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody (Ab), accumulation of IgG4-expressing plasmacytes in the affected organs, and involvement of multiple organs. It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity. However, a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype. In addition, disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone. Therefore, it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD. Recently, we found that activation of plasmacytoid dendritic cells producing both interferon-α (IFN-α) and interleukin-33 (IL-33) mediate murine AIP and human IgG4-RD. More importantly, we provided evidence that serum concentrations of IFN-α and IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders. In this Frontier article, we have summarized and discussed biomarkers of AIP and IgG4-RD, including Igs, autoAbs, and cytokines to provide useful information not only for clinicians but also for researchers.     

The present status of the clinical laboratory medicine in Cambodia

The educational system and the introduction of legislation of clinical medicine are both still in developing stage in Cambodia where only 10 years have passed since the establishment of a new government. In order to maintain good health of all Cambodian citizens and to improve the quality of care in health services, it should be necessary to implement an appropriate educational system for both laboratory technologists and technicians. To conduct refreshment training course for laboratory workers with provision of the instruments, material and reagents is another way to make improvement of it in public hospitals. It should be also required to overcome economic problems how to absorb medical expense and to understand the importance for doctors to diagnose with scientific data of clinical examinations. Maturation of the total medical system in this country should be necessary and suggestions from neighboring countries with views toward the world standard would be expected.