A Prospective Randomized Clinical Trial of Combination Therapy with Proton Pump Inhibitors and Mucolytics in Patients with Laryngopharyngeal Reflux.

OBJECTIVES: To identify whether combination therapy with mucolytics and proton pump inhibitors (PPIs) leads to faster and more effective symptomatic relief in patients with laryngopharyngeal reflux (LPR). METHODS: Patients diagnosed as LPR with a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7 were enrolled in this prospective study. Patients were randomly allocated to control (PPI only) or experimental (PPI + mucolytics) groups and changes in RSI and RFS values were assessed at 1- and 3-month follow-up. RESULTS: One hundred sixteen patients were randomly allocated into either the control group (n = 59) or the experimental group (n = 57). The RSI and RFS scores significantly decreased in both groups (all P < .001) after 1 month of treatment; however, there was no significant difference in RSI change between groups (P = .223). After 3 months of treatment, there remained no significant difference in RSI change between groups (P = .592). CONCLUSIONS: Combination therapy with mucolytics and PPI compared to PPI alone did not lead to faster or more effective symptomatic relief in LPR patients.

Comparison of microinsulated needle radiofrequency and carbon dioxide laser ablation for the treatment of syringoma.

Syringoma is a benign adnexal tumor originating from the intradermal eccrine ducts and predominantly occurs in women at puberty or later in life. We present a case of a 30-year-old woman with a 2-year history of syringoma on her neck and axillar region. She was treated with two devices in a split manner. The right-sided lesions of the neck were treated with one session of 10,600-nm carbon dioxide (CO2 ) laser ablation. The left-sided lesions were treated with microinsulated needle radiofrequency (RF) three times. After treatment, the lesions treated with CO2 showed hypertrophic scar formation, but the other side lesions treated with microinsulated needle RF showed a marked reduction in the size and number of lesions, without any adverse effects such as scarring and hyperpigmentation related to epidermal damage. The treatment of syringoma with microinsulated needle RF, which is insulated at the point of epidermal contact, results in good cosmetic outcomes. Syringoma, microinsulated needle RF, CO2 laser.

Nuclear translocation of CAM-associated protein activates transcription for long-term facilitation in Aplysia.

Repeated pulses of serotonin (5-HT) induce long-term facilitation (LTF) of the synapses between sensory and motor neurons of the gill-withdrawal reflex in Aplysia. To explore how apCAM downregulation at the plasma membrane and CREB-mediated transcription in the nucleus, both of which are required for the formation of LTF, might relate to each other, we cloned an apCAM-associated protein (CAMAP) by yeast two-hybrid screening. We found that 5-HT signaling at the synapse activates PKA which in turn phosphorylates CAMAP to induce the dissociation of CAMAP from apCAM and the subsequent translocation of CAMAP into the nucleus of sensory neurons. In the nucleus, CAMAP acts as a transcriptional coactivator for CREB1 and is essential for the activation of ApC/EBP required for the initiation of LTF. Combined, our data suggest that CAMAP is a retrograde signaling component that translocates from activated synapses to the nucleus during synapse-specific LTF.

Evidence for a role of CaMKIV in the development of opioid analgesic tolerance.

cAMP response-element binding protein (CREB), a transcription factor involved in learning, memory and drug addiction, is phosphorylated by calcium-calmodulin-dependent protein kinase IV (CaMKIV). Here, we show that CaMKIV-knockout (KO) mice developed less analgesic tolerance after chronic morphine administration with no alteration in physical dependence or acute morphine-induced analgesia. The increase in phosphorylated CREB expression observed in wild-type mice after chronic morphine was absent in CaMKIV-KO mice, while there was no difference in the expression or phosphorylation of the micro-opioid receptor between groups. Morphine-treated CaMKIV-KO mice showed less G-protein uncoupling from the micro-opioid receptor than did wild-type mice, while uncoupling was similar in control wild-type and KO mice. In addition, morphine reduced inhibitory transmission to a greater degree in CaMKIV-KO mice than in controls after chronic morphine exposure. Our results provide novel evidence for the role of CaMKIV in the development of opioid analgesic tolerance but not physical dependence.

Cofilin expression induces cofilin-actin rod formation and disrupts synaptic structure and function in Aplysia synapses.

Cofilin-actin rods are inclusion-like structures that are induced by certain chemical or physical stresses in cultured cells, and the rods formed in neurons are thought to be associated with neurodegeneration. Here, we cloned an Aplysia cofilin homolog and overexpressed it in cultured neurons. Overexpressed cofilin formed rod-like structures that included actin. The overall neuronal morphology was unaffected by cofilin overexpression; however, a decrease in number of synaptic varicosities was observed. Consistent with this structural change by cofilin overexpression, the synaptic strength was reduced, and furthermore, the long-term facilitation elicited by repeated pulses of 5-hydroxytryptamine was impaired in sensory-to-motor synapses. However, cofilin overexpression did not induce programmed cell death. These findings suggest that the formation of cofilin-actin rod-like structures can lead to neurodegeneration, and this might be a mechanism of rundown of neuronal and synaptic function without cell death in neurodegenerative diseases.

Thiol oxidation-mediated cell death in Aplysia cultured sensory neurons.

Cellular thiol groups modulate various aspects of cellular function, including cell death. In this study, we found that a thiol oxidant, diamide, induced morphological changes such as cell swelling, membrane blebbing, and chromatin condensation in Aplysia cultured sensory neurons. Furthermore, diamide induced biphasic changes in the membrane potential, where hyperpolarization was followed by depolarization. Moreover, these diamide-induced cytotoxic effects were completely blocked by the equimolar addition of the disulfide reducing agent dithiothreitol (DTT). We also found that during H(2)O(2)-induced cell death, DTT attenuated cell swelling and membrane blebbing, but not DNA breakage, whereas the vitamin E analogue trolox attenuated DNA breakage, but not cell swelling and membrane blebbing. These results demonstrate that during H(2)O(2)-induced cell death, apoptotic features such as DNA breakage are mediated in part by free radical generation, whereas necrotic features such as cell swelling and membrane blebbing are primarily mediated by the oxidation of cellular thiol groups.