Saffron therapy for the ongoing treatment of age-related macular degeneration.

OBJECTIVE: To assess the long-term efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS AND ANALYSIS: Open-label, extension trial of 93 adults (>50 years) with mild/moderate AMD and vision >20/70 Snellen equivalent in at least 1 eye. Exclusion criteria included confounding visual lesions or significant gastrointestinal disease impairing absorption.Participants were given oral saffron supplementation (20 mg/day) for 12 months. Those already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these.Primary outcomes included changes in multifocal electroretinogram (mfERG) response density and latency, and changes in best-corrected visual acuity (BCVA). Secondary outcomes included safety outcomes, changes in mfERG and BCVA among participants on AREDS supplements and changes in microperimetry. RESULTS: At 12 months, mean mfERG response density was significantly higher in rings 1, 2 and overall (p<0.001 for all) but not in rings 3-6, and there was no difference in response between those taking AREDS supplements and those not (p>0.05). Mean mfERG latency was not significantly different in any of rings 1-6 or overall (p>0.05 for all), again with no difference between those taking AREDS supplements or not (p>0.05). Mean BCVA was 1.6 letters worse (p<0.05) with no difference between those on AREDS supplements or not, and this may have been related to cataract progression. No saffron-related serious adverse events were detected. CONCLUSION: Saffron supplementation modestly improved mfERG responses in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.

Complications, Treatment, and Outcomes of Self-Injecting Substances Into the Face: A Systematic Review.

BACKGROUND: The increased demand for minimally invasive facial cosmetic procedures in tandem with the ease of acquiring injectable cosmetics through direct-to-consumer retailers has led to a rise in self-injecting cosmetics among untrained individuals. OBJECTIVE: To analyze complications, treatments, and outcomes associated with self-injecting fillers into the face. METHODS: A systematic review of the literature from PubMed and Embase databases was performed from inception to September 10, 2022, to identify studies pertaining to self-injection of facial fillers. RESULTS: A total of 15 articles describing 38 complications among 18 patients were included in the data collection. The most commonly injected substance was hyaluronic acid (76.4%). The lips were the most common site of injection (33%). The most reported complication was edema (61%). Severe complications included acute vascular compromise (11%) and acute hearing loss (5%). The most common intervention was use of hyaluronidase and/or antibiotics (87.5%). Patients generally healed after treatment although residual localized hyperpigmentation was noted among 11% of patients. CONCLUSION: Injecting commercially available substances into the face is associated with potentially irreversible aesthetic, infectious, and vascular complications, especially in the hands of untrained consumers. Patients and providers should be aware of this dangerous trend.

Factors Influencing Graduates of American Academy of Facial Plastic and Reconstructive Surgery Fellowships Career Choice of Academic or Private Practice: A 20-Year Review.

Background: Absence of published literature on facial plastic and reconstructive surgery (FPRS) fellows' pursuit of academic careers hampers informed decision making for those interested in the specialty, fellowship program directors, and leaders in the American Academy of Facial Plastic and Reconstructive Surgery. Objective: To examine career choices among FPRS fellows from 2000 to 2019 and identify factors linked to academic or private practice employment after fellowship. Methods: Data from 796 fellows were analyzed, including gender, medical school, residency program, fellowship program, fellowship year, and degrees, to categorize them based on academic or nonacademic career placement. Logistic regression analyses were conducted to explore the association between demographic factors and academic career placement. Results: Forty-three percent (n = 345) obtained academic positions, with significant associations found between academic placement and additional advanced degrees, completion of fellowship training in the northeast, and residency training at an institution offering FPRS fellowship. Conclusion: Although fellows in FPRS predominantly pursue private practice, the decision to pursue academia is influenced by complex and multifactorial factors among graduates in the field.

Understanding the Impact of Aging on Attractiveness Using a Machine Learning Model of Facial Age Progression.

Background: Advances in machine learning age progression technology offer the unique opportunity to better understand the public's perception on the aging face. Objective: To compare how observers perceive attractiveness and traditional gender traits in faces created with a machine learning model. Methods: Eight surveys were developed, each with 10 sets of photographs that were progressively aged with a machine learning model. Respondents rated attractiveness and masculinity or femininity of each photograph using a sliding scale (range: 0-100). Mean attractiveness scores were calculated and compared between men and women as well as between age groups. Results: A total of 315 respondents (51% men, 49% women) completed the survey. Accuracy of the facial age progression model was 85%. Females were considered significantly less attractive (-10.43, p < 0.01) and less feminine (-7.59, p < 0.01) per decade with the greatest drop over age 40 years. Male attractiveness and masculinity were relatively preserved until age 50 years where attractiveness scores were significantly lower (-5.45, p = 0.39). Conclusions: In this study, observers were found to perceive attractiveness at older ages differently between men and women.

Complications associated with costal cartilage harvest in pediatric laryngotracheal reconstruction.

Objective: We aimed to determine the rate of complications associated with autologous costal cartilage graft harvest for pediatric laryngotracheal reconstruction (LTR). Secondarily, we sought to identify risk factors associated with the harvest of autologous costal cartilage, as well as evaluate management strategies. Data Sources: An electronic database search of Ovid MEDLINE, Ovid EMBASE, and PubMed was completed for articles pertaining to complications in autologous costal cartilage harvest for pediatric LTR. Review Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The study characteristics, operative information, and patient demographics were collected. The data concerning postoperative complications, risk factors, and management strategies were collected and analyzed for patterns. Results: A total of 31 manuscripts representing 745 patients were included for analysis. The reported donor site complications included pneumothorax (n = 13, 1.74%), pleural tear (n = 5, 0.67%), infection (n = 8, 1.07%), and scar-related problems (n = 2, 0.26%). There were no reported cases of seroma, persistent pain, or chest wall deformity. Only five studies discussed the management of donor site complications, with intervention in 11 (39.28%) patients including chest tube drainage and steroid injection. Conclusion: There is significant variability in the literature regarding complication rates in autologous costal cartilage harvest for pediatric LTR. The incidence of major postoperative complications is low and supports the use of autologous costal cartilage as graft material for pediatric LTR. Level of Evidence: NA.

Comparison of Nasal Obstruction Symptom Evaluation Score Outcomes After Autologous Cartilage Grafts and Latera Nasal Implants.

OBJECTIVE: To compare quantitative Nasal Obstruction Symptom Evaluation (NOSE) scores for ACG and Latera implants for nasal valve repair. METHODS: Retrospective chart review of patients who underwent ACG or Latera placement between January 2016 through May 2019 by a single surgeon. Patients who had completed NOSE surveys pre- and post-operatively were identified and eligible for inclusion. Data regarding baseline demographic characteristics, adjunctive surgical procedures, NOSE scores at 1, 3, and 6-month post-operative visits, complications, and total operative time were collected. Unpaired t-tests and linear mixed models were performed to analyze differences between study groups. RESULTS: There were 24 and 39 patients who underwent ACG and Latera, respectively, who met eligibility criteria. There were no differences in demographic characteristics or pre-operative baseline NOSE scores (ACG: 65.1 and Latera: 64.4; P = .92) between groups. Mean operative times were not significantly different between groups (ACG: 113 minutes and Latera: 102 minutes; P = .76). Within each group, NOSE scores were significantly improved at each post-operative visit compared to pre-operative baselines. Between groups, mean NOSE scores were lower at each post-operative visit for ACG compared to Latera (1-month ACG: 21.7 and Latera: 45.9, P = .002 ; 3-month ACG: 14.5 and Latera: 39.9, P = .034; 6-month ACG: 8.4 and Latera: 44.2, P = .003). CONCLUSIONS: Both ACG and Latera offer significant improvements in patient-reported nasal obstruction severity; however, ACG may yield more favorable subjective symptom scores.

Social Perception of Self-Enhanced Photographs.

The use of appearance manipulating applications on our smartphones has increased in popularity. As the aim of this study is to determine the impact of self-directed appearance manipulation on perceptions of personality and examine the influence of respondent age and gender on the various personality domains. This cross-sectional cohort study included 20 subjects between the ages of 18 to 34 who had headshots taken and were provided an introduction on the use of the Facetune2 app. After 1 week of engaging in digital appearance manipulation, subjects submitted their self-determined most attractive edited photograph. Four surveys were constructed with 10 sets of photographs each. Each of these surveys were then sent to lay people via a web-based survey tool. Anonymous blinded respondents used a 7-point Likert scale to rate their perception of each patient's aggressiveness, likeability, sociability, trustworthiness, attractiveness, authenticity, and masculinity or femininity. A multivariate linear mixed effect model was applied to analyze the overall patient trait data as well as to assess the impact of rater age and gender. A total of 288 respondents (mean age range, 25-34 years [43%]; 202 [70%] female) completed a survey. Overall, digitally enhanced photographs were perceived as more attractive (0.22; 95% CI, 0.06-0.38). Analysis based on gender of the study subjects revealed increased attractiveness scores for men (0.19; 95% CI, 0.07-0.33). Females were also perceived as being more attractive (0.16; 95% CI, 0.03-0.40), but less authentic (-0.24; 95% CI, -0.36 to -0.12). Females rated enhanced photographs of men as less masculine (-0.23; 95% CI, -0.46 to -0.04). Raters aged 35 to 64 rated altered photos as less attractive (0.31; 95% CI, 0.09-0.52), authentic (0.20; 95% CI, 0.01-0.38), and gender enhancing (0.42; 95% CI, 0.24-0.61) compared with individuals aged 18 to 34. Patients and surgeons should be aware of the ways in which self-enhanced photographs may affect social perception.

Quantitative Analysis of Enhanced Selfies in a Young Adult Population.

The use of filters and editing tools for perfecting selfies is increasing. While some aesthetic experts have touted the ability of this technology to help patients convey their aesthetic goals, others have expressed concerns about the unrealistic expectations that may come from the ability for individuals to digitally alter their own photos in these so-called "super-selfies." The aim of the study is to determine the changes that individuals seek when enhancing selfies. Twenty subjects participated in this study between July 25 and September 24, 2019. Subjects had two sets of headshots taken (neutral and smile) and were provided an introduction on the use of the Facetune2 app. Subjects received a digital copy of their photographs and were asked to download the free mobile app. After 1 week of trialing the different tools for enhancing their appearance, subjects submitted their self-determined most attractive edited photographs. Changes in marginal reflex distance (MRD) 1 and 2, nose height and width, eyebrow height, facial width, skin smoothness, skin hue, and saturation as well as overall image brightness were recorded. Paired two-tailed t-test was used to evaluate pre- and post-facial measurements. There were no statistically significant changes identified in the analysis of the altered photos in neutral expression. Analysis of all smiling photographs revealed that subjects increased their smile angle (right: +2.92 mm, p = 0.04; left: +3.58 mm, p < 0.001). When smiling photographs were assessed by gender, females were found to significantly increase their MRD2 (right: +0.64 mm, p = 0.04; left: +0.74 mm, p = 0.05) and their smile angle (right: +1.90 mm, p = 0.03; left: +2.31 mm, p = 0.005) while also decreasing their nose height (-2.8 mm, p = 0.04). Males did not significantly alter any of the facial measurements assessed. This study identifies the types of changes that individuals seek when enhancing selfies and specifies the different aspects of image adjustment that may be sought based on a patient's gender.

Comparison between two multimodal imaging platforms: Nidek Mirante and Heidelberg Spectralis.

PURPOSE: To investigate the reliability and comparability of retinal measurements obtained with spectral-domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), confocal scanning laser ophthalmoscopy (cSLO) colour images, and fundus autofluorescence (FAF) between two multimodal imaging platforms in eyes with macular pathology and normal, healthy volunteers. METHODS: This cross-sectional, multi-centre, instrument validation study recruited 94 consecutive subjects. All participants underwent a dilated examination and were scanned consecutively on the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Nidek Mirante (Nidek Co. Ltd., Gamagori, Japan) devices. Agreement between device images were evaluated from measures of the central retinal thickness (CRT), presence of segmentation and fixation imaging artefacts (IA), foveal avascular zone (FAZ) measurements; as well as sensitivity and specificity values from the detection of atrophy on fundus autofluorescence (FAF), drusen, subretinal drusenoid deposits, geographic atrophy, epiretinal membrane, fibrosis and haemorrhage on multicolour imaging, and agreement between devices and groups. RESULTS: Compared with reference clinical examination, sensitivity values for the identification of retinal features using sole device images ranged from 100% for epiretinal membranes to 66.7% for subretinal drusenoid deposits (SSD). Mean absolute difference for CRT between OCT devices was 3.78 µm (95% confidence interval [CI]: - 21.39 to 28.95, P = 0.809). Differences in the superficial and deep capillary plexus FAZ area on OCTA between devices were not statistically significant (P = 0.881 and P = 0.595, respectively). IAs were significantly increased in the presence of macular pathology. CONCLUSION: Comparison of retinal measurements between the OCT devices did not differ significantly. Common ultrastructural biomarkers of multiple macular pathologies were identified with high sensitivities and specificities, with good agreement between graders, indicating that they can be identified with comparable confidence in retinal imaging between the two devices.

The Role of Age and Gender on Perception of Women After Cosmetic Rhinoplasty.

BACKGROUND: Rhinoplasty is known to increase attractiveness; however, the influence of observer age and gender are largely undetermined. METHODS: This retrospective cross-sectional study included 20 women who underwent cosmetic rhinoplasty between January 1st, 2012, and December 31st, 2019. A total of 4 surveys were constructed with 10 sets of photographs each (5 preoperative and 5 postoperative). Surveys were designed such that photographs of the same patient were not placed in the same survey to avoid recall bias. Each of these surveys were then sent to at least 30 lay people via a web-based survey tool. Anonymous blinded respondents used a 7-point Likert scale to rate their perception of each patient's aggressiveness, likeability, sociability, trustworthiness, attractiveness, femininity, intelligence and confidence. A multivariate linear mixed effect model was applied to analyze the overall patient trait data as well as to assess age and gender differences. RESULTS: This survey study included photographs of 20 women (mean age, 28.2 years) before and after cosmetic rhinoplasty. A total of 174 respondents (mean age range, 25-34 years [41%]; 108 [62%] were female) completed the survey. Overall, postoperative photographs were perceived as significantly more sociable (0.13; 95% CI, 0.01-0.25), attractive (0.21; 95% CI, 0.09-0.34), feminine (0.18; 95% CI, 0.05-0.30), and confident (0.15; 95% CI, 0.02-0.27). When analyzed by sex, men rated women as less aggressive (-0.42, 95% CI, -0.65,-0.17) and more likeable (+0.45, 95% CI, 0.21-0.69), sociable (+0.38, 95% CI, 0.14-0.62), trustworthy (+0.37, 95% CI, 0.13-0.61), attractive (+0.60, 95% CI, 0.35-0.84), feminine (+0.23, 95% CI, 0.07-0.41) and intelligent (+0.29, 95% CI, 0.04-0.53). In contrast, female respondents indicated an increase in perceived attractiveness (+0.16, 95% CI, 0.06-0.22) and femininity (+0.18, 95% CI, 0.03-0.32) for women after rhinoplasty. Raters aged 25-34 indicated improvements across all traits analyzed. Almost all age ranges rated post-operative photographs as more attractive (18-24: +0.32, 95% CI, 0.19-0.46; 25-34: +0.52, 95% CI, 0.33-0.72; 35-44: +0.29, 95% CI, 0.12-0.51; 45-54: +0.50, 95% CI, 0.11-0.89) while individuals over age 55 only indicated increased trustworthiness (+0.51, 95% CI, 0.03-0.99). CONCLUSIONS: These findings suggest that cosmetic rhinoplasty improves perceptions of personality and physical traits of women with males and individuals aged 25-34 indicating the greatest benefit. LEVEL OF EVIDENCE: Level IV.

Complex Nasal Fractures in the Adult-A Changing Management Philosophy.

Acute management of complex nasal fractures in the adult nose is still frequently conducted using closed reduction techniques as first-line therapy. Treatment outcomes from closed reduction are often disappointing and secondary surgical corrections are required in a sizeable subset of patients. In response to the shortcomings of closed fracture manipulation, classic rhinoplasty techniques have been introduced to improve anatomic fracture reduction. Although these techniques improve the accuracy of skeletal reduction, they also weaken the nose, leaving it susceptible to the deformational forces of healing. To provide optimal anatomic fracture reduction and concomitant stabilization of the skeletal framework, we have been using contemporary strategies derived from open structure rhinoplasty and extracorporeal septal reconstruction for initial fracture treatment. Using wide-field exposure with open rhinoplasty, these strategies provide optimal fracture reduction and rigid stabilization of the septal L-strut using suture-based fixation and structural grafting techniques. The result is unsurpassed contour restoration and lasting architectural stability of the nose. When combined with power-driven instruments to cut, shape, mobilize, and create osseous suture holes, open structure stabilization of the disrupted skeletal framework establishes a new benchmark in acute fracture management.

Teaching and assessing endoscopic sinus surgery skills on a validated low-cost task trainer.

OBJECTIVES/HYPOTHESIS: To evaluate a previously validated low-cost sinus surgery task trainer as a means of acquiring basic endoscopic sinus surgery skills and as an objective structured assessment of technical skills (OSATS) to determine procedural competency. STUDY DESIGN: Prospective blinded study. METHODS: Medical students (N = 52) with no sinus surgery experience learned to perform nasal endoscopy and five specific sinus surgery tasks using the validated task trainer. Training included regimented expert instruction, peer instruction/observation, and experienced-based learning. Pre- and post-training video recordings of nasal endoscopy and five sinus surgery skills were obtained. Two blinded expert otolaryngologists compared pre- and post-training performance using a checklist and global rating scale. RESULTS: Medical student post-training performance was significantly better than pre-training performance for each checklist item and global rating scale as calculated by paired t test (P < .001). Interrater reliability and internal consistency were confirmed by Kendall's coefficient of concordance and Cronbach's α calculations, respectively. CONCLUSIONS: The sinus surgery task trainer provides an effective means of teaching and evaluating nasal endoscopy and basic sinus surgery skills for novice surgeons. With repeated practice, there was significant improvement in performance. An OSATS using the sinus surgery task trainer suggests that we can effectively measure endoscopic sinus surgery ability with the potential to reliably determine competency outside the operating room.

ORL emergencies boot camp: using simulation to onboard residents.

OBJECTIVES/HYPOTHESIS: Incoming otolaryngology residents are expected to triage and manage airway, bleeding, and other emergencies with little prior experience. Simulation-based education has become increasingly important as it provides tools to develop psychomotor skills and judgment early in residency, using realistic experiences while eliminating patient risk. We hypothesize that a Boot Camp course emphasizing basic otolaryngology management will increase participants' confidence and be perceived as useful in developing their knowledge, technical skills, self-confidence, and improving clinical performance, both immediately and 6 months following the course. STUDY DESIGN: Survey. METHODS: A 1-day Boot Camp was developed consisting of six technical skills stations (mask ventilation, intubation, flexible laryngoscopy, microlaryngoscopy/bronchoscopy, epistaxis control, and cricothyroidotomy); a session involving telephone inquiry triage, and two complex airway scenarios addressing medical management and emphasizing team leadership. Residents completed questionnaires before, immediately, and 6 months following course completion. RESULTS: Thirty residents enrolled, 27 participated in the course, and 24 completed all three surveys. Previous experiences and confidence levels were variable; 26 of 30 (87%) identified emergency airway management as a concern before attending the course. A Fisher's exact test demonstrated improved confidence (P < .05) for every skill. An overwhelming majority of participants agreed or strongly agreed the intervention was useful in developing their knowledge, technical skills, self-confidence, and improving clinical performance. CONCLUSIONS: An intensive, simulation-based Boot Camp addressing airway, bleeding, and other otolaryngology emergencies was successful in improving junior otolaryngology residents' confidence and was perceived as useful in developing knowledge, technical skills, self-confidence, and improving clinical performance.

Temperature dependence of photochemical fluorescence fading in Skh-1 hairless mouse collagen.

BACKGROUND: Type I mammalian collagens have several photolabile fluorescent moieties that absorb UV rays capable of reaching the dermis. We studied the temperature dependence of fluorescence fading as a marker of photochemical damage. METHODS: Collagen solutions were exposed to radiation from 0 to 240 min from either a UVG-11 hand lamp, total dose=1.173 x 10(3) J/m(2); a UVL-21 hand lamp total dose=2.030 x 10(3) J/m(2); or the fluorometer, at 325+/-5 nm, total dose=0.156 x 10(3) J/m(2). We recorded intensities at excitation/emission wavelengths 270/300, 270/330, 270/360, 270/400, 325/400, and 370/450 nm at T=9.0-59.3 degrees C. RESULTS: Results indicated simultaneous forward and reverse reactions. However, the 270/360 nm fluorophore could be analyzed as a second-order reaction. The Arrhenius curve showed two straight lines intersecting near the denaturation temperature, with helix activation energy E(a) approximately 0 and coil E(a)=7.6+/-0.6 kcal/mol (31.7+/-2.5 kJ/mol). DISCUSSION: Collagen-bound fluorophores are not just passive markers of oxidative stress and age-related damage. Their photolability to wavelengths reaching the dermis may result in pathological conditions, particularly at elevated body temperatures.

PD128,907 induces ocular hypotension in rabbits: involvement of D2/D3 dopamine receptors and brain natriuretic peptide.

The purpose of this study was to determine the potential role of brain natriuretic peptide (BNP) in the PD128,907 (a dopamine D2/D3 receptor agonist)-induced ocular hypotension in rabbits. The effects of topical application of PD128,907 (75, 250, 750 microg) on intraocular pressure (IOP) were investigated. The lowest dose (75 microg) did not alter IOP; while the higher doses (250 and 750 microg) reduced IOP bilaterally. The PD128,907 (250 microg)-induced ocular hypotension, which lasted 3 hours, could be blocked by raclopride (1000 microg), a dopamine D2/D3 receptor antagonist, as well as by sympathetic denervation. Aqueous humor inflow was reduced by intravitreal injection of PD128,907 (10 microg) by 67% at 1 and 2 hours, which then returned to baseline at 3 hours. Furthermore, topical application of PD128,907 (250 microg) elevated aqueous BNP levels by 3-fold at 30 minutes, 6-fold at 1 hour and 5-fold at 2 hours, which could be blocked by pretreatment with raclopride (250 microg). Taken together, PD128,907-induced ocular hypotension by activation of dopamine D2/D3 receptors. This action was associated with reduced aqueous humor inflow and increased aqueous BNP levels.

7-OH-DPAT-induced inhibition of norepinephrine release in PC12 cells.

The purpose of this study was to investigate mechanisms of suppression of norepinephrine release by 7-OH-DPAT, a dopamine D(2)/D(3) receptor agonist, in PC12 cells pretreated with nerve growth factor (NGF). 7-OH-DPAT caused inhibition of basal and K(+)-evoked norepinephrine release, which could be blocked by pretreatment with raclopride, a D(2)/D(3) receptor antagonist. Moreover, dopamine D(2) and D(3 )receptors were identified by immunocytochemistry. Expression of D(2), D(3), and D(4) mRNAs and their proteins were detected using RT-PCR and immunoblotting. Furthermore, 7-OH-DPAT produced no change in cGMP levels; however, 7-OH-DPAT inhibited forskolin-stimulated cAMP accumulation that was antagonized by pretreatment with raclopride. In addition, 7-OH-DPAT inhibited carbachol-induced Ca(2+) transient, conversely, 7-OH-DPAT had no effect on 4-aminopyridine-induced Ca(2+) transient. Taken together, suppression of cAMP accumulation and calcium mobilization by 7-OH-DPAT is involved in the inhibition of norepinephrine release through activation of dopamine D(2)/D(3) receptors.

CNP-induced changes in pHi, cGMP/cAMP and mRNA expression of natriuretic peptide receptors in human trabecular meshwork cells.

It has been demonstrated that natriuretic peptides lower intraocular pressure, however, the underlying cellular mechanism(s) mediating this response remain(s) to be determined. The purpose of this study was to investigate the effects of C-type natriuretic peptide (CNP) on pH(i), cGMP/cAMP and expression of atrial natriuretic peptide receptor (NPR-A), brain natriuretic peptide receptor (NPR-B) and C-type natriuretic peptide receptor (NPR-C), in HTM cells. At concentrations of 10(-7) M, CNP caused an acidification of pH(i). In addition, CNP caused a dose-dependent increase in cGMP formation and inhibition of forskolin-stimulated cAMP accumulation. These changes were not significantly altered in the absence of 10(-3) M isobutylmethylxanthine (IBMX). Treatment with the NPR-A antagonist, anantin, produced no influence on basal cGMP/cAMP levels, the CNP-stimulated cGMP accumulation and CNP-induced inhibition of forskolin-stimulated cAMP accumulation. However, CNP-induced reduction of forskolin-stimulated cAMP accumulation was inhibited by pretreatment with pertussis toxin (PTX). Furthermore, NPRB receptors were predominantly expressed and pretreatment with CNP (10(-7) M, 24hr) enhanced all NPR mRNAs expression which was not altered by higher concentrations or longer incubation. Results demonstrate that NPR-A, NPR-B and NPR-C receptors' expression can be up-regulated by CNP treatment. CNP activates NPR-B receptors preferentially to increase cGMP accumulation and acts through the PTX-sensitive cAMP-signaling pathway leading to a decrease in pH(i).

4-aminopyridine transiently increases intraocular pressure in rabbits.

The purpose of this study is to determine the mechanisms of action involved in the ocular hypertension induced by 4-aminopyridine (4-AP), a voltage-dependent potassium (K+) channel blocker, in rabbits. Topical application of 4-AP elevated intraocular pressure (IOP). This action caused increases in the aqueous flow rate as well as aqueous levels of protein and norepinephrine. In isolated iris-ciliary body preparations, 4-AP (0.01, 0.1, 1 mmol/l) caused dose-related increases in field-stimulated norepinephrine release by 43, 222 and 243%, respectively. Taken together, the IOP-elevating effect evoked by 4-AP was associated with enhancement of aqueous norepinephrine levels and norepinephrine release from sympathetic nerves of the iris-ciliary body. These results demonstrate that the 4-AP-sensitive K+ channels in sympathetic nerves and the ciliary epithelium are the potential sites of action of the 4-AP-induced ocular hypertension.