Angiotensin II activates intermediate-conductance Ca2+ -activated K+ channels in arterial smooth muscle cells

Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.     

High–dose rate brachytherapy alone in postoperative soft tissue sarcomas with close or positive margins

PurposeIn the management of soft tissue sarcomas, perioperative radiation therapy has been used to reduce the risk of local recurrence after resection. However, a significance of postoperative high–dose rate brachytherapy (HDRBT) remains to be studied. Retrospective analysis was performed to elucidate the role of postoperative HDRBT.Methods and MaterialsTwenty-five patients with 26 soft tissue sarcoma lesions underwent postoperative HDRBT using ¹⁹²Ir remote afterloader without external beam radiation therapy. Ninety-two percent of the lesions were Grade 2 or 3 malignancies, and 50% were resected with positive surgical margins. The remaining 50% had very close margins. Fourteen lesions were treated for local recurrences after previous resections. Applicators of HDRBT were placed during the operation to include only the tumor bed excluding surgical scars. Applied dose was mainly 36 Gy/6 fractions/3 d b.i.d.ResultsFive-year local recurrence-free survival was 78.2% in all the 26 lesions. Recurrences were not seen within the treated volume of HDRBT. Two groups were defined according to the marginal status and number of previous operations. Group 1 was the lesions with a positive margin and foregoing resections. The remaining lesions were classified as Group 2. Five-year local recurrence-free survival was 43.8% and 93.3% in Group 1 and Group 2, respectively with a statistically significant difference (p = 0.004).ConclusionsPostoperative HDRBT was effective in controlling local lesions; but in Group 1 lesions, addition of a wide field external beam radiation therapy seems to be necessary to improve the local control rate.     

Factors associated with household transmission of SARS-CoV-2 omicron variant to health care workers: A retrospective cohort study

Aim

The aim of this study was to determine the risk factors for household transmission of the omicron variant of SARS-CoV-2.

Background

The household infection rate has been reported to be higher for the omicron variant than for non-omicron variants of SARS-CoV-2. Determination of the risk factors for household transmission of the omicron variant is therefore important.

Design

A Retrospective Cohort Study was conducted.

Methods

When family members of health care workers (HCWs) were found to be infected with SARS-CoV-2, the HCWs had to receive two nucleic acid amplification tests for SARS-CoV-2: immediately after and 5 to 10 days after the onset of COVID-19 in the family members. Risk factors of household transmission were analysed by comparing cases (HCWs infected with SARS-CoV-2) and controls (HCWs not infected with SARS-CoV-2) using multivariable analysis.

Results

Unvaccinated status (OR: 3.97), age of index cases (≤6 years) (OR: 1.94) and staying at home with index cases (OR: 10.18) were risk factors for household transmission.

Conclusion

If there is a strong desire to avoid household infection, family members infected with SARS-CoV-2 should live separately during the period of viral shedding.