Patient Preferences and Comparative Outcomes Regarding Cryosurgery versus Electrodesiccation in the Removal of Truncal Seborrheic Keratoses.

Background: Seborrheic keratoses (SKs) are one of the most common benign epithelial tumors seen by dermatologists. Many people elect to have these lesions removed, most commonly by way of cryosurgery or electrodesiccation. Objective: We sought to evaluate the comparative efficacy and patient preferences regarding cryosurgery and electrodesiccation for the treatment of truncal SK lesions. Methods: In this randomized, blinded clinical trial, 33 eligible subjects with two similar truncal SKs were assigned to receive treatment with cryosurgery and electrodesiccation applied to separate lesions. Patients rated their pain and preference at the time of treatment and follow up at two and eight weeks. Physicians rated the color, texture, and efficacy of lesion removal at eight weeks. Results: Patients did not have a treatment preference (p=0.10) and there was no significant difference in pain when comparing cryosurgery to electrodesiccation (p=0.43). Both treatment modalities were similar in terms of efficacy (p=0.50). Skin texture was rated similarly (p=0.64); however, lesions treated with cryosurgery were nominally less likely to have posttreatment hyperpigmentation compared to lesions treated with electrodesiccation (odds ratio: 0.35, 95% confidence interval: 0.12-1.002; p=0.0504). Conclusion: Cryosurgery and electrodesiccation are both effective treatment modalities for truncal SKs. While cosmetic outcomes were similar, cryosurgery resulted in less postinflammatory hyperpigmentation.

Down-regulation of endogenous KLHL1 decreases voltage-gated calcium current density.

The actin-binding protein Kelch-like 1 (KLHL1) can modulate voltage-gated calcium channels in vitro. KLHL1 interacts with actin and with the pore-forming subunits of Cav2.1 and CaV3.2 calcium channels, resulting in up-regulation of P/Q and T-type current density. Here we tested whether endogenous KLHL1 modulates voltage gated calcium currents in cultured hippocampal neurons by down-regulating the expression of KLHL1 via adenoviral delivery of shRNA targeted against KLHL1 (shKLHL1). Control adenoviruses did not affect any of the neuronal properties measured, yet down-regulation of KLHL1 resulted in HVA current densities ~68% smaller and LVA current densities 44% smaller than uninfected controls, with a concomitant reduction in α(1A) and α(1H) protein levels. Biophysical analysis and western blot experiments suggest Ca(V)3.1 and 3.3 currents are also present in shKLHL1-infected neurons. Synapsin I levels, miniature postsynaptic current frequency, and excitatory and inhibitory synapse number were reduced in KLHL1 knockdown. This study corroborates the physiological role of KLHL1 as a calcium channel modulator and demonstrates a novel, presynaptic role.

Calcium current homeostasis and synaptic deficits in hippocampal neurons from Kelch-like 1 knockout mice.

Kelch-like 1 (KLHL1) is a neuronal actin-binding protein that modulates voltage-gated CaV2.1 (P/Q-type) and CaV3.2 (α1H T-type) calcium channels; KLHL1 knockdown experiments (KD) cause down-regulation of both channel types and altered synaptic properties in cultured rat hippocampal neurons (Perissinotti et al., 2014). Here, we studied the effect of ablation of KLHL1 on calcium channel function and synaptic properties in cultured hippocampal neurons from KLHL1 knockout (KO) mice. Western blot data showed the P/Q-type channel α1A subunit was less abundant in KO hippocampus compared to wildtype (WT); and P/Q-type calcium currents were smaller in KO neurons than WT during early days in vitro, although this decrease was compensated for at late stages by increases in L-type calcium current. In contrast, T-type currents did not change in culture. However, biophysical properties and western blot analysis revealed a differential contribution of T-type channel isoforms in the KO, with CaV3.2 α1H subunit being down-regulated and CaV3.1 α1G up-regulated. Synapsin I levels were also reduced in the KO hippocampus and cultured neurons displayed a concomitant reduction in synapsin I puncta and decreased miniature excitatory postsynaptic current (mEPSC) frequency. In summary, genetic ablation of the calcium channel modulator resulted in compensatory mechanisms to maintain calcium current homeostasis in hippocampal KO neurons; however, synaptic alterations resulted in a reduction of excitatory synapse number, causing an imbalance of the excitatory-inhibitory synaptic input ratio favoring inhibition.