Urinary iodine kinetics after oral loading of potassium iodine

We studied the kinetics of iodine in various forms, in order to establish appropriate guidelines of iodine prophylaxis for thyroid blockade at nuclear emergency in "iodine rich areas", such as Japan. First, the effect of equivalent dose of potassium iodide (KI) (solution vs. tablet) was evaluated with excretions of urinary iodine (UI) at Nagasaki, Japan, and it was revealed that there was no difference of iodine kinetics between solution and tablet. We also performed the same study at Gomel, Belarus, which was known to be an iodine deficient area, and obtained the same results. Second, the kinetics of iodine included in "iodine rich" food was also evaluated with excretions of UI. Interestingly, the ratio of UI excretion with iodine rich food was significantly lower than that with KI tablets until 6 h after the intake (ANOVA, p = 0.02). These results proved that 1) KI solution as well as its tablet is useful for prophylaxis and 2) prophylaxis by iodine rich food is not effective for rapid blockade of thyroid gland at nuclear emergency. Finally, we emphasized that the approach from social medicine is definitely important to establish an effective iodine prophylaxis.     

Integrins play a critical role in mechanical stress-induced p38 MAPK activation

Mechanical stress activates various hypertrophic responses, including activation of mitogen-activated protein kinases (MAPKs) in cardiac myocytes. Stretch activated extracellular signal-regulated kinases partly through secreted humoral growth factors, including angiotensin II, whereas stretch-induced activation of c-Jun NH(2)-terminal kinases and p38 MAPK was independent of angiotensin II. In this study, we examined the role of integrin signaling in stretch-induced activation of p38 MAPK in cardiomyocytes of neonatal rats. Overexpression of the tumor suppressor PTEN, which inhibits outside-in integrin signaling, strongly suppressed stretch-induced activation of p38 MAPK. Overexpression of focal adhesion kinase (FAK) antagonized the effects of PTEN, and both tyrosine residues at 397 and 925 of FAK were necessary for its effects. Stretch induced tyrosine phosphorylation and activation of FAK and Src. Stretch-induced activation of p38 MAPK was abolished by overexpression of FAT and CSK, which are inhibitors of the FAK and Src families, respectively, and was suppressed by overexpression of a dominant-negative mutant of Ras. Mechanical stretch-induced increase in protein synthesis was suppressed by SB202190, a p38 MAPK inhibitor. These results suggest that mechanical stress activates p38 MAPK and induces cardiac hypertrophy through the integrin-FAK-Src-Ras pathway in cardiac myocytes.     

Improved cardioprotection using a novel stepwise ischemic preconditioning protocol in rabbit heart

Background

The current commonly used cardiac ischemic preconditioning (IPC) protocol, involving three 5-min cycles of ischemia–reperfusion (I/R), may not be clinically beneficial because of its acutely deleterious effects on hemodynamics. This study attempted to assess the effects of a novel stepwise IPC scheme on cardiac function, infarct size, and arrhythmogenesis in a rabbit model of prolonged I/R.

Methods

Anesthetized open-chest rabbits were subjected to 60-min occlusion of a proximal branch of the left coronary artery followed by 180-min reperfusion. Animals were divided into five groups (n = 6 each): (1) control group (no IPC); (2) 2-min IPC group (three cycles of 2-min IPC); (3) 5-min IPC group (three cycles of 5-min IPC); (4) 10-min IPC group (three cycles of 10-min IPC); and (5) stepwise IPC group (2-, 5-, and 10-min I/R).

Results

Compared with control group, 2-, 5-, and 10-min IPC decreased arrhythmia score by 16%, 67%, and 33%, respectively. Remarkably, stepwise IPC resulted in a 78% reduction of arrhythmias. Stepwise IPC also produced the least ventricular infarct size when compared with 2-, 5-, and 10-min IPC groups (16.4% versus 39.3%, 28.1%, and 38.5%, P < 0.05).

Conclusions

These results suggest that stepwise IPC has better cardioprotective effects against prolonged I/R injury and may serve as an acceptable approach to clinical revascularization procedures on the heart, including catheter-based and surgical approaches.     

Two new alkaloids from Crinum asiaticum var. japonicum

Journal of Natural Medicines - A new crinine-type alkaloid crijaponine A (1), a new galanthamine-type alkaloid crijaponine B (2), and 11 known alkaloids—ungeremine (3), lycorine (4),...     

Practices of receptive and insertive anal sex among transgender women in relation to partner types,sociocultural factors,and background variables

It is urgent to develop efficacious HIV prevention programs to curb the reported extremely high HIV prevalence and incidence among transgender women (male-to-female transgender persons) who reside in large cities in the USA. This study aimed to describe unprotected receptive anal sex (URAS) and unprotected insertive anal sex (UIAS) among high-risk transgender women in relation to partner types, psychosocial factors, and background variables. Based on purposive sampling from the targeted communities and AIDS service organizations in San Francisco and Oakland, a total of 573 transgender women who had a history of sex work were recruited and individually interviewed using a structured survey questionnaire. Significant correlates with URAS with primary, casual, and commercial sex partners were found (e.g., needs for social support, frequency of social support received, exposure to transphobia, self-esteem, economic pressure, norms toward practicing healthy behaviors, and self-efficacy toward practicing safe sex). Multiple logistic regression analyses revealed that transgender women who had engaged in URAS with commercial partners were more likely to have higher levels of transphobia or lower levels of the norms or self-efficacy to practice safe sex. Among the participants who did not have vaginoplasty (preoperative transgender women), 16.4% had engaged in insertive anal sex (IAS) with commercial partners in the past 30 days. The participants who were HIV positive and had engaged in IAS were more likely to be African-American or Caucasians, coinfected with sexually transmitted infections, or identified themselves as homosexual. Practices of IAS among transgender women have not been thoroughly investigated in relation to sexual and gender identity. UIAS with homosexual and bisexual men in addition to URAS may be a cause for high HIV incidence among transgender women. An HIV prevention intervention study must be developed and evaluated, which aims to reduce HIV-positive and -negative transgender women's URAS and UIAS.     

A case of complex suicide due to acute nicotine intoxication caused by cigarette ingestion

International Journal of Legal Medicine - This paper presents an unusual complex suicide case that died of nicotine addiction. The deceased was a 40-year-old male who was found lying dead on the...     

TAM receptors attenuate murine NK-cell responses via E3 ubiquitin ligase Cbl-b

TAM receptors (Tyro3, Axl, and Mer) are receptor tyrosine kinases (RTKs) that are expressed by multiple immune cells including NK cells. Although RTKs typically enhance cellular functions, TAM receptor ligation blocks NK-cell activation. The mechanisms by which RTKs block NK-cell signaling downstream of activating receptors are unknown. In this report, we demonstrate that TAM receptors attenuate NK cell responses via the activity of E3 ubiquitin ligase Casitas B lineage lymphoma b (Cbl-b). Specifically, we show that Tyro3, Axl, and Mer phosphorylate Cbl-b, and Tyro3 ligation activates Cbl-b by phosphorylating tyrosine residues 133 and 363. Ligation of TAM receptors by their ligand Gas6 suppresses activating receptor-stimulated NK-cell functions such as IFN-γ production and degranulation, in a TAM receptor kinase- and Cbl-b-dependent manner. Moreover, Gas6 ligation induces the degradation of LAT1, a transmembrane adaptor protein required for NK cell activating receptor signaling, in WT but not in Cbl-b knock-out NK cells. Together, these results suggest that TAM receptors may attenuate NK-cell function by phosphorylating Cbl-b, which in turn dampens NK-cell activation signaling by promoting the degradation of LAT1. Our data therefore support a mechanism by which RTKs attenuate, rather than stimulate, signaling pathways via the activation of ubiquitin ligases.