ELF-MF Stimulates Adrenal Steroidogenesis

Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression is considered to involve adrenal steroidogenesis, which is triggered by ELF-MF exposure. However, how ELF-MFs stimulate adrenal steroidogenesis is controversial. In the current study, we investigated the effect of ELF-MF exposure on the mouse adrenal cortex-derived Y-1 cell line and the human adrenal cortex-derived H295R cell line to clarify whether the ELF-MF stimulates adrenal steroidogenesis directly. ELF-MF exposure was found to significantly stimulate adrenal steroidogenesis (p < 0.01–0.05) and the expression of adrenal steroid synthetic enzymes (p < 0.05) in Y-1 cells, but the effect was weak in H295R cells. Y-1 cells exposed to an ELF-MF showed significant decreases in phosphodiesterase activity (p < 0.05) and intracellular Ca2+ concentration (p < 0.01) and significant increases in intracellular cyclic adenosine monophosphate (cAMP) concentration (p < 0.001–0.05) and cAMP response element-binding protein phosphorylation (p < 0.05). The increase in cAMP was not inhibited by treatment with NF449, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study

A propensity score matching study on robot-assisted radical cystectomy for older patients : comparison of intracorporeal ileal conduit and cutaneous ureterostomy

Background: Robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion are less invasive than conventional procedures. However, for older patients, cutaneous ureterostomy (CUS) may be preferred because urinary diversion using the intestine has a high incidence of perioperative complications and is highly invasive. The purpose of this study was to demonstrate the safety and efficacy of intracorporeal ileal conduit (ICIC) compared with CUS in patients aged 75 years or older who underwent RARC. Methods: From October 2014 to December 2021, 82 patients aged 75 years or older who underwent RARC at Tokushima University Hospital, Tokushima Prefectural Central Hospital, or Ehime Prefectural Central Hospital were retrospectively reviewed. Of these, 52 and 25 patients who underwent ICIC and CUS, respectively, were included. After adjusting the patients’ characteristics using propensity score-matching, surgical results and prognoses were retrospectively compared. The propensity score was based on age, Eastern Cooperative Oncology Group Performance Status Scale (ECOG-PS), American Society of Anesthesiologists physical status classification (ASA-PS), clinical tumor stage, and neoadjuvant chemotherapy. Results: The median age was lower in the ICIC group compared with the CUS group, and the proportion of high-risk cases (ECOG-PS ≥ 2 or ASA-PS ≥ 3) did not differ. The median operation time was longer in the ICIC group, and estimated blood loss was higher, compared with the CUS group. There were no significant differences in the incidence of complications within the first 30 postoperative days, incidence of complications 30–90 days after surgery, 2 year overall survival, 2-year cancer-specific survival, and 2-year recurrence-free survival. The stent-free rate was significantly lower in the CUS group than that in the ICIC group. Conclusion: In older patients, the ICIC group showed non-inferior surgical and oncological outcomes compared with the CUS group. Urinary diversion following RARC in older patients should be carefully selected by considering not only the age but also the general condition (including comorbidities) of the patient

Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line

<div><p>Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression is considered to involve adrenal steroidogenesis, which is triggered by ELF-MF exposure. However, how ELF-MFs stimulate adrenal steroidogenesis is controversial. In the current study, we investigated the effect of ELF-MF exposure on the mouse adrenal cortex-derived Y-1 cell line and the human adrenal cortex-derived H295R cell line to clarify whether the ELF-MF stimulates adrenal steroidogenesis directly. ELF-MF exposure was found to significantly stimulate adrenal steroidogenesis (p < 0.01–0.05) and the expression of adrenal steroid synthetic enzymes (p < 0.05) in Y-1 cells, but the effect was weak in H295R cells. Y-1 cells exposed to an ELF-MF showed significant decreases in phosphodiesterase activity (p < 0.05) and intracellular Ca²⁺ concentration (p < 0.01) and significant increases in intracellular cyclic adenosine monophosphate (cAMP) concentration (p < 0.001–0.05) and cAMP response element-binding protein phosphorylation (p < 0.05). The increase in cAMP was not inhibited by treatment with NF449, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study.</p></div

Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line - Fig 6

<p><b>Signaling pathways regulating adrenal steroidogenesis (A) and the assumed steroidogenic mechanism induced by ELF-MF exposure (B).</b> AC: adenylate cyclase, cAMP: cyclic adenosine monophosphate, CaM: calmodulin, CaMK: calmodulin kinase, CREB: cAMP response element binding protein, DAG: diacylglycerol, GPCR: G protein-coupled receptor, IP3: inositol triphosphate, PDE: phosphodiesterase, PKA: protein kinase A, PKC: protein kinase C, PLC: phospholipase C, 5′ AMP: adenosine 5'-monophosphate.</p

Effects of ELF-MF and sham exposure on steroid secretion and enzyme expression in H295R cells.

<p>All data are presented as the mean ± S.E.M. Cortisol (A) and aldosterone (B) secretion did not show a significant difference between sham and ELF-MF exposure. (C) After 24 h of ELF-MF and sham exposure, mRNA expression of <i>Star</i> showed a significant increase in ELF-MF-exposed cells. (D) No significant increase was observed in protein levels. A representative blot image is shown (lanes 1 and 3: sham-exposed sample; lanes 2 and 4: ELF-MF-exposed sample). Steroid levels were quantified twice per sample (culture dish), and qRT-PCR and western blotting were performed once. n = 8 each, *p < 0.05, **p < 0.01.</p

Intracellular cAMP concentration was estimated in Y-1 cells exposed to ELF-MF and sham treatments.

<p>All data are presented as the mean ± S.E.M. (A) cAMP levels were significantly higher upon exposure to a 1.5-mT ELF-MF than after sham exposure for all durations (n = 8 each). (B) CREB phosphorylation was significantly higher in the ELF-MF group than in the sham group with 24 h of exposure (n = 8 each). (C) The 340/380 nm emission Fura ratio, which indicates [Ca²⁺]_i, was significantly lower in cells exposed to 24-h ELF-MF treatment (n = 10) than in sham-exposed cells (n = 10). cAMP levels were quantified twice per sample (dish). The Fura ratio was estimated once per sample. *p < 0.05, **p < 0.01, ***p < 0.001.</p

Genes quantified in this study, along with the corresponding primer sequences and probe numbers from the Universal ProbeLibrary.

<p>Genes quantified in this study, along with the corresponding primer sequences and probe numbers from the Universal ProbeLibrary.</p

Effects of ELF-MF and sham exposure on steroid secretion and enzyme expression in Y-1 cells.

<p>Data are presented as the mean ± S.E.M. Corticosterone (A) and aldosterone (B) levels were significantly higher after 6 h of ELF-MF exposure. (C) <i>Cyp11a1</i> and <i>Cyp11b2</i> mRNA levels showed a significant increase after 24 h of exposure to the ELF-MF as indicated by qRT-PCR results. (D) Secreted CYP11A1 protein levels were significantly increased as indicated by western blotting. A representative blot image is shown (lanes 1 and 3: sham-exposed samples; lanes 2 and 4: ELF-MF- exposed samples). Steroids were quantified twice per sample (culture dish), and qRT-PCR and western blotting were performed once. n = 8 each, *p < 0.05, **p < 0.01 vs. sham exposure.</p

Effect of NF449 on the increase in cAMP concentration resulting from ELF-MF exposure.

<p>All data are presented as the mean ± S.E.M. (A) NF449 inhibited the increase in cAMP concentration in Y-1 cells exposed to sham treatment and 1.5 mT ELF-MF for 6 h; however, the cAMP-increasing effect of ELF-MF was still significantly higher than that of the sham treatment after 30 μM NF449 treatment (n = 8 each). (B) PDE activity was significantly lower in ELF-MF- than in sham-exposed Y-1 cells at both 6 h and 24 h (n = 4 each). cAMP and PDE were quantified twice per sample. *p < 0.05, **p < 0.01.</p