ß2-adrenergic receptor expression and the effects of norepinephrine and propranolol on various head and neck cancer subtypes.

The present study aimed to investigate expression of ß2-adrenergic receptor (AR), the effect of the stress-related neurotransmitter norepinephrine (NE) on cell viability, proliferation and the therapeutic effect of propranolol, which is a typical ß-blocker in various type of head and neck cancers for the first time. The ß2-AR expression was investigated using immunohistochemistry and an immunoreactive scoring (IRS) system in 57 different head and neck cancer specimens, and reverse transcriptase-polymerase chain reaction and western blotting in four head and neck cancer cell lines (HNCCLs). Cell viability and proliferation assays were performed using 0, 1, 5 and 10 µM of NE and 1 µM of propranolol in four HNCCLs. The expression of ß2-AR was positive in the majority of head and neck cancer tissues (55/57, 96.5%); however, it was significantly higher in oral cavity cancer than in pharyngeal cancer (median IRS: 9 vs. 3; P<0.001). All HNCCLs exhibited ß2-AR expression, with a higher expression level detected in the oral cavity cancer cell line than in the others. NE stimulated viability (oral cavity, 206%; larynx, 156%; pharynx, 130%; nasal cavity, 137%; 10 µM NE) and proliferation (124, 176, 131 and 127%, respectively) in a dose-dependent manner in all HNCCLs. Conversely, propranolol attenuated such viability (55, 42, 18 and 22%, respectively) and proliferation (22, 40, 61 and 48%, respectively). In conclusion, the viability and proliferation of various head and neck cancers may be directly stimulated by stress and this may be attenuated by ß-blockers.

Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats.

Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p < 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects.

Botulinum Toxin Injection for Chronic Parotitis: A Multi-Center and Prospective Trial.

OBJECTIVE: When conservative therapy fails for chronic parotitis, sialendoscopic treatment or surgical excision can be considered. However, these are financially costly or invasive. Thus, this study aimed to evaluate the clinical efficacy and safety of botulinum toxin (BTX) injection and to further analyze its effect on parotid gland function and volume using salivary single-photon emission computed tomography (SPECT)-computed tomography (CT). METHODS: This clinical trial has been registered in the Clinical Research Information Service, Republic of Korea. Fourteen patients with chronic parotitis received BTX injections into the parotid glands. Pain, postprandial pain, swelling, aesthetic discomfort, and salivary flow rate were assessed before injection, at 2 weeks, and at 1, 3, and 6 months. Salivary SPECT-CT was performed before injection and again 3 and 6 months after to assess the volume and uptake changes. RESULTS: All subjective symptoms decreased significantly until 1 month and then increased. However, at 6 months, all subjective symptoms were determined to be better than before injection. The unstimulated and stimulated salivary flow rate did not show a significant difference over time. No significant difference was noted in parotid gland volume or uptake on salivary SPECT-CT over time. CONCLUSION: BTX injection can be an alternative treatment option for chronic parotitis. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1903-E1909, 2021.

Clinical Presentation, Management, and Prognostic Factors of Idiopathic Systemic Capillary Leak Syndrome: A Systematic Review.

BACKGROUND: The idiopathic systemic capillary leak syndrome is a rare disease characterized by unexplained recurrent shock caused by capillary hyperpermeability. Because of the rarity of the disease, this disease has easily been misdiagnosed and evidence of efficacious agents used empirically is lacking. OBJECTIVE: To analyze the clinical and laboratory data, treatment modalities, and mortality rate of patients and to find contributing factors leading to mortality. METHODS: We searched MEDLINE (inception to December 2016) and reviewed reference lists of previous systematic reviews. A total of 133 case reports (161 patients) and 5 case series (102 patients) of idiopathic systemic capillary leak syndrome were included. RESULTS: Patients had hypotension (81.4%), edema (64.6%), and previous flu-like illness (34.2%). This disease was misdiagnosed as hypovolemic shock, septic shock, polycythemia vera, or angioedema. Thirty-seven patients died (23%) mainly because of systemic capillary leak syndrome itself (78.4%). There were significant differences in the survival rates between patients who were treated with prophylactic ß2 agonists, methylxanthines, and intravenous immunoglobulins and those who were not. The estimated 1-, 5-, and 10-year survival rate of patients treated with intravenous immunoglobulins was 100%, 94%, and 94%, respectively. CONCLUSIONS: We systematically analyzed in detail clinical presentations of all reported patients and identified various factors associated with mortality and effects of prophylactic treatment in idiopathic systemic capillary leak syndrome. The findings of this review will facilitate diagnostic approaches of idiopathic systemic capillary leak syndrome and aid in the selection of treatment.