Comparison of nasal valve dysfunction treatment outcomes for temperature-controlled radiofrequency and functional rhinoplasty surgery: a systematic review and meta-analyses.

BACKGROUND: Nasal valve dysfunction (NVD) is a substantial contributor to nasal airway obstruction. Minimally-invasive temp-erature-controlled radiofrequency (TCRF) treatment of the nasal valve is available and comparison with surgical techniques is warranted. METHODOLOGY: Databases: Medline (PubMed), Embase, Cochrane Library. POPULATION: adults with preprocedural nasal obstruction symptom evaluation (NOSE) score >=45. Treatment effects were derived from a random effects model and reported as weighted mean difference in NOSE score between baseline; 3, 6, and 12 months postprocedure. RESULTS: Of 2529 initial articles, 5 studies describing TCRF treatment and 63 studies describing functional rhinoplasty were included. Pooled effect sizes for TCRF treatment and functional rhinoplasty were comparable in all analyses. CONCLUSIONS: TCRF treatment of the internal nasal valve for NVD was associated with sustained effects comparable to functional rhinoplasty addressing the nasal valve only, rhinoplasty without concomitant turbinate treatment, and all rhinoplasty.

Two-year outcomes of radiofrequency device treatment of the nasal valve for nasal airway obstruction.

BACKGROUND: Temperature-controlled radiofrequency (TCRF) device treatment of nasal valve dysfunction (NVD) was superior to a sham procedure control in reducing the symptoms of nasal airway obstruction (NAO) in this randomised controlled trial (RCT). METHODOLOGY: Two-year outcomes for 108 patients actively treated in a prospective, multicenter, patient-blinded RCT were used to determine treatment effect durability and changes in medication/nasal dilator usage. A responder was defined as ≥ 20 reduction in NOSE score or 1 reduction in severity class. RESULTS: The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) women. Baseline NOSE score was 76.3. The 2-year responder rate was 90.4% and NOSE score treatment effect was -41.7; 54.7% improvement. Of 57 patients using medications/nasal dilators at baseline, 45 (78.9%) either stopped all use (33.3%) or stopped/decreased (45.6%) use in >=1 class at 2 years. Concurrent septal deviation, septal swell body, or turbinate enlargement did not significantly affect the odds of exhibiting a NOSE score of ≤ 25 at 2 years. CONCLUSIONS: TCRF device treatment of NVD resulted in significant and sustained improvements in the symptoms of NAO at 2 years, accompanied by a substantial reduction in medication/nasal dilator use.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Mepolizumab in CRSwNP/ECRS and NP: the phase III randomised MERIT trial in Japan, China, and Russia.

BACKGROUND: This randomised, double-blind, placebo-controlled, parallel-group, 52-week Phase III study (MERIT; NCT04607005) assessed mepolizumab efficacy and safety in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS (ECRS) in Japan, Russia, and China, for which data are limited. METHODOLOGY: Eligible patients (enrolled at 60 centres) had blood eosinophil count >2%, endoscopic bilateral NP score ≥5, nasal obstruction visual analogue scale (VAS) score >5, ≥2 sinonasal symptoms, and either previous sinus surgery or systemic corticosteroid use/intolerance. Patients were randomised (1:1) to receive mepolizumab 100 mg subcutaneously or placebo every 4 weeks, plus standard of care. Co-primary endpoints: change from baseline in total endoscopic NP score (ENPS) (Week 52) and nasal obstruction VAS score (Weeks 49-52). Post hoc analyses conducted in a modified intent-to-treat (mITT) population excluded patients from two study sites, related to Good Clinical Practice violations by the Site Management Organisation overseeing these sites. These were considered the primary efficacy analyses. RESULTS: In the mITT population, mepolizumab (n=80) versus placebo (n=83) significantly improved nasal obstruction VAS score from baseline to Week 49-52 and was associated with a trend of total ENPS improvements at Week 52. Mepolizumab/placebo on-treatment adverse events (AEs) occurred in 68/84 and 65/85 patients in the safety population (treatment-related AEs: 2/84 and 5/85, respectively), and on-treatment serious AEs in 0/84 and 4/85 patients, respectively (no fatalities reported). CONCLUSIONS: Mepolizumab was effective and well-tolerated in patients with CRSwNP/ECRS from Japan, Russia, and China.

Evaluating treatment response to mepolizumab in patients with severe CRSwNP.

BACKGROUND: The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP). METHODS: SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS). RESULTS: Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across >=3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories). CONCLUSIONS: Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

[Analysis of current status and influencing factors of inflammatory factors among electrical workers in Hainan province].

Objective: To analyze the level and influence factors of inflammatory factors among electrical workers in Hainan Province. Methods: A total of 509 electrical workers were selected as the research subjects with random cluster sampling in September 2020. Basic information was collected by questionnaire, the serum IL-6, IL-8 and TNF-α levels of the subjects were detected by Luminex.Mann-Whitney U test and Kruskal-wallis H test were used for univariate analysis. Ordinal logistic regression analysis was used for potential influencing factors of the level of inflammatory factors. Results: The median concentrations of IL-6, IL-8 and TNF-α in serum were 2.78, 9.77 and 8.18 pg/ml. Compared with women, male was a risk factor for the increase of IL-6 levels (OR=1.80, 95%CI: 1.08~3.00, P=0.024) . Compared with 51-60 years old, 21-31 years old (OR=0.27, 95%CI: 0.18~0.42, P<0.001) , 31-41 years old (OR=0.27, 95%CI: 0.17~0.43, P<0.001) and 41-51 years old (OR=0.64, 95%CI: 0.41~0.99, P=0.043) were protective factors for the increase of IL-8 level. Compared with day shift workers, shift work was a risk factor for the increase of IL-8 level (OR=1.73, 95%CI: 1.21~2.48, P=0.003) . Compared with women, male was a risk factor for the increase of TNF-α levels (OR=2.87, 95%CI: 1.70~4.86, P<0.001) . Compared with workers who exposed to 7 or more occupational hazard factors, exposed to 1~3 (OR=0.53, 95%CI: 0.30~0.92, P=0.024) occupational hazard factors were protective factors for the increase of TNF-α levels. Conclusion: The level of inflammatory factors was related to sex, age, work system and occupational environment, which can provide basic data for follow-up research on occupational population.

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

Probing strongly exchange coupled magnetic behaviors in soft/hard Ni/CoFe2O4 core/shell nanoparticles.

Exchange coupling in a model core-shell system is demonstrated as a step on the path to 3d exchange spring magnets. Employing a model system of Ni@CoFe2O4, high quality core-shell nanoparticles were fabricated using a simple two-step method. The microstructural quality was validated using TEM, confirming a well-defined interface between the core and the shell. A strongly temperature dependent two-phase magnetic hysteresis loop was measured, wherein an analysis of step heights indicates coupling of roughly 50% between the core and the shell. Element-specific XMCD hysteresis confirms the presence of exchange coupling, suppressing the superparamagnetism of the Ni core at room temperature, and reaching a coercivity of >6 kOe at 80 K. These results provide a pathway to the development of heterostructured metal-oxide exchange coupled nanoparticles with improved maximum energy product.

EUFOREA summit in Brussels 2023: inspiring the future of allergy & respiratory care.

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

Inositol 1,4,5-trisphosphate-induced calcium release in the organelle layers of the stratified, intact egg of Xenopus laevis.

Using double-barreled, Ca2(+)-sensitive microelectrodes, we have examined the characteristics of the Ca2+ release by inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) in the various layers of Xenopus laevis eggs in which the organelles had been stratified by centrifugation. Centrifugation of living eggs stratifies the organelles yet retains them in the normal cytoplasmic milieu. The local increase in intracellular free Ca2+ in each layer was directly measured under physiological conditions using theta-tubing, double-barreled, Ca2(+)-sensitive microelectrodes in which one barrel was filled with the Ca2+ sensor and the other was filled with Ins(1,4,5)P3 for microinjection. The two tips of these electrodes were very close to each other (3 microns apart) enabling us to measure the kinetics of both the highly localized intracellular Ca2+ release and its subsequent removal in response to Ins(1,4,5)P3 injection. Upon Ins(1,4,5)P3 injection, the ER-enriched layer exhibited the largest release of Ca2+ in a dosage-dependent manner, whereas the other layers, mitochondria, lipid, and yolk, released 10-fold less Ca2+ in a dosage-independent manner. The removal of released Ca2+ took place within approximately 1 min. The sensitivity to Ins(1,4,5)P3 and the time course of intracellular Ca2+ release in the unstratified (unactivated) egg is nearly identical to that observed in the ER layer of the stratified egg. Our data suggest that the ER is the major organelle of the Ins(1,4,5)P3-sensitive Ca2+ store in the egg of Xenopus laevis.

Reducing inositol lipid hydrolysis, Ins(1,4,5)P3 receptor availability, or Ca2+ gradients lengthens the duration of the cell cycle in Xenopus laevis blastomeres.

We have microinjected a mAb specifically directed to phosphatidylinositol 4,5-bisphosphate (PIP2) into one blastomere of two-cell stage Xenopus laevis embryos. This antibody binds to endogenous PIP2 and reduces its rate of hydrolysis by phospholipase C. Antibody-injected blastomeres undergo partial or complete arrest of the cell cycle whereas the uninjected sister blastomeres divided normally. Since PIP2 hydrolysis normally produces diacylglycerol (DG) and inositol 1,4,5-triphosphate (Ins[1,4,5]P3), we attempted to measure changes in the levels of DG following stimulation of PIP2 hydrolysis in antibody-injected oocytes. The total amount of DG in antibody-injected oocytes was significantly reduced compared to that of water-injected ones following stimulation by either acetylcholine or progesterone indicating that the antibody does indeed suppress PIP2 hydrolysis. We also found that the PIP2 antibodies greatly reduced the amount of intracellular Ca2+ released in the egg cortex during egg activation. As an indirect test for Ins(1,4,5)P3 involvement in the cell cycle we injected heparin which competes with Ins(1,4,5)P3 for binding to its receptor, and thus inhibits Ins(1,4,5)P3-induced Ca2+ release. Microinjection of heparin into one blastomere of the two-cell stage embryo caused partial or complete arrest of the cell cycle depending upon the concentration of heparin injected. We further investigated the effect of reducing any [Ca2+]i gradients by microinjecting dibromo-BAPTA into the blastomere. Dibromo-BAPTA injection completely blocked mitotic cell division when a final concentration of 1.5 mM was used. These results suggest that PIP2 turnover as well as second messenger activity influence cell cycle duration during embryonic cell division in frogs.

The involvement of cAMP signaling pathway in axis specification in Xenopus embryos.

The cAMP signaling system has been postulated to be involved in embryogenesis of many animal species, however, little is known about its role in embryonic axis formation in vertebrates. In this study, the role of the cAMP signaling pathway in patterning the body plan of the Xenopus embryo was investigated by expressing and activating the exogenous human 5-hydroxytryptamine type 1a receptor (5-HT(1a)R) which inhibits adenylyl cyclase through inhibitory G-protein in embryos in a spatially- and temporally-controlled manner. In embryos, ventral, but not dorsal expression and stimulation of this receptor during blastula and gastrula stages induced secondary axes but were lacking anterior structures. At the molecular level, 5-HT(1a)R stimulation induced expression of the dorsal mesoderm marker genes, and downregulated expression of the ventral markers but had no effect on expression of the pan mesodermal marker gene in ventral marginal zone explants. In addition, ventral expression and stimulation of the receptor partially restored dorsal axis of UV-irradiated axis deficient embryo. Finally, the total mass of cAMP differs between dorsal and ventral regions of blastula and gastrula embryos and this is regulated in a temporally-specific manner. These results suggest that the cAMP signaling system may be involved in the transduction of ventral signals in patterning early embryos.

Identification and developmental expression of par-6 gene in Xenopus laevis.

The par genes (partitioning defective) are required to establish polarity in the Caenorhabditis elegans embryo. We have identified the Xenopus homologue of C. elegans PAR-6 (XPAR-6). XPAR-6 is a protein of 377 amino acids with one PDZ domain which is involved in mediating protein-protein interactions. It shares 59% and 58% amino acid identity with the mouse and Drosophila PAR-6, respectively, and 54% overall identity with C. elegans PAR-6. Xpar-6 is expressed both maternally and zygotically. Xpar-6 is first detected in the animal half of the egg, and this pattern of expression persists into the cleavage and blastula stages. At the gastrula stage, the message is detected in animal pole area and in a broad domain of ventral region, but is excluded from dorsal region. With the onset of neurulation, the localized expression of Xpar-6 becomes more obvious, leading to it being enriched in the dorsolateral region along the lateral edges of neural plate and anterior presumptive head region surrounding the anterior border of neural plate. At late tailbud stage, Xpar-6 transcripts show localized expression throughout the head, labeling the branchial arches, eyes, otic vesicles and brain, while more posteriorly Xpar-6 labels the somites, pronephros, tail tip and proctodeum. Therefore, this analysis suggests that Xpar-6 has a regionalized pattern of expression during Xenopus early embryogenesis.

Poly(A) binding protein II in Xenopus laevis is expressed in developing brain and pancreas.

We have isolated Xenopus homolog of poly(A) binding protein II (XPABPII) and examined its expression during early embryogenesis and embryonic gut development. XpabpII encodes a nuclear protein of 296 amino acids that contains an alpha-helical coiled-coil domain and a ribonucleoprotein-type RNA binding domain. XpabpII is expressed both maternally and zygotically. In gastrula and neurula embryos, XpabpII is expressed mainly in ectoderm, neural and epidermal. From tailbud through to tadpole stages, the neural tissue specific expression of XpabpII gradually becomes confined to the specific vesicle regions of developing brain, being detected in the eye, olfactory pit, telencephalon and mesencephalon, but being excluded from the diencephalon region. Intriguingly, XpabpII transcripts are observed in differentiating gut endoderm. XpabpII first becomes visible in the anterior part of a stage 35 embryonic gut in which prospective liver, stomach and pancreas are located. During further development, uniform expression in anterior gut gradually becomes restricted to the pancreas rudiment. At the seventh day of development, when the gut has formed a complex coiled structure in which each organ contains clearly differentiated cell type, XpabpII is detectable exclusively in the pancreas. Taken together, we suggest that XpabpII plays a specific role in the polyadenylation process of genes involved in brain and pancreas development.

Switching bipolar hepatic radiofrequency ablation using internally cooled wet electrodes: comparison with consecutive monopolar and switching monopolar modes.

OBJECTIVE: To evaluate whether switching bipolar radiofrequency ablation (SB-RFA) using three internally cooled wet (ICW) electrodes can induce coagulations >5 cm in porcine livers with better efficiency than consecutive monopolar (CM) or switching monopolar (SM) modes. METHODS: A total of 60 coagulations were made in 15 in vivo porcine livers using three 17-gauge ICW electrodes and a multichannel radiofrequency (RF) generator. RF energy (approximately 200 W) was applied in CM mode (Group A, n = 20) for 24 min, SM mode for 12 min (Group B, n = 20) or switching bipolar (SB) mode for 12 min (Group C, n = 20) in in vivo porcine livers. Thereafter, the delivered RFA energy, as well as the shape and dimension of coagulations were compared among the groups. RESULTS: Spherical- or oval-shaped ablations were created in 30% (6/20), 85% (17/20) and 90% (18/20) of coagulations in the CM, SM and SB groups, respectively (p = 0.003). SB-RFA created ablations >5 cm in minimum diameter (Dmin) in 65% (13/20) of porcine livers, whereas SM- or CM-RFA created ablations >5 cm in only 25% (5/20) and 20% (4/20) of porcine livers, respectively (p = 0.03). The mean Dmin of coagulations was significantly larger in Group C than in Groups A and B (5.1 ± 0.9, 3.9 ± 1.2 and 4.4 ± 1.0 cm, respectively, p = 0.002) at a lower delivered RF energy level (76.8 ± 14.3, 120.9 ± 24.5 and 114.2 ± 18.3 kJ, respectively, p < 0.001). CONCLUSION: SB-RFA using three ICW electrodes can create coagulations >5 cm in diameter with better efficiency than do SM- or CM-RFA. ADVANCES IN KNOWLEDGE: SB-RFA can create large, regular ablation zones with better time-energy efficiency than do CM- or SM-RFA.

Modulation of lysophosphatidic acid-induced Cl- currents by protein kinases A and C in the Xenopus oocyte.

The roles of protein kinase C (PKC) and protein kinase A (PKA) in the regulation of lysophosphatidic acid (LPA)-induced Cl- currents in Xenopus oocytes were examined. PKC activation by phorbol 12-myristate 13-acetate (PMA) treatment completely blocked LPA-induced Cl- currents by inhibiting inositol 1,4,5-trisphosphate (IP3) elevation. This inhibitory effect of PMA on the LPA response was blocked by pretreatment of oocytes with staurosporine and 3-[N-(dimethylamino)propyl-3-indiolyll-4-[3-indolyl]maleimide (GF109203X), PKC inhibitors. In addition, treatment of oocytes with GF109203X enhanced the LPA response by increasing IP3 production. Elevation of the intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration by treating oocytes with either forskolin (FK) plus isobutylmethylxanthine (IBMX) or 2'-O-dibutyryl-cAMP (dB-cAMP) reduced LPA-induced Cl- currents. The effect of activation of the cAMP pathway appears to be mediated by PKA, since treatment of oocytes with FK plus IBMX or dB-cAMP enhanced PKA activity. Furthermore, the inhibitory effect of dB-cAMP on the LPA response was blocked by treatment of oocytes with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulframide-2 HCl (H-89), a selective inhibitor of PKA. Both FK plus IBMX and dB-cAMP treatment reduced IP3 generation in response to LPA stimulation. Inhibition of PKA activity with H-89 or Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium had no effect on LPA-induced Cl- currents. Finally, inhibition of the LPA response by activation of PKA was independent of extracellular Ca2+. These results demonstrate that both PKC and PKA play active roles in modulating the LPA-induced signaling pathway.

Comparison of harmonic and conventional power Doppler ultrasonography for assessment of slow flow in hyperechoic tissue: experimental study using a Doppler phantom.

RATIONALE AND OBJECTIVES: Despite the advantages of depicting slow flow in small vessels, conventional power Doppler ultrasound (US) has a basic limitation, specifically that artifactual power Doppler signals mimic blood flow, especially in hyperechoic tissue. The purpose of this study was to compare harmonic power Doppler US with power Doppler US using a Doppler phantom under various parameter settings, focusing on the assessment of slow flow in the hyperechoic tissue. METHODS: While controlling the flow velocity (5 and 10 cm/s), pulse repetition frequency (500, 700, and 1,000 Hz), wall filter (low and medium), and Doppler gain (90%, 96%, and 100%), the authors performed both harmonic Doppler US and power Doppler US by using a Doppler phantom/flow control system. We measured and compared the relative intensities of the Doppler signals (0-250 scale) in both the vessels and hyperechoic tissue-mimicking materials with the two different imaging modalities. RESULTS: Power Doppler US with any combination of the four parameters evaluated depicted strong flow signals (mean, 213) that were superior to harmonic Doppler US (mean, 61). Relatively strong artifactual signals within the hyperechoic tissue-mimicking materials were noted on all power Doppler US studies (mean, 106) but nearly none on harmonic Doppler US (mean, 3). The contrast-to-noise ratio of harmonic Doppler US was significantly greater than that of power Doppler US. CONCLUSIONS: Harmonic Doppler US is more useful in assessing slow flow in hyperechoic tissue than power Doppler US because it produces fewer artifactual Doppler signals originating from stationary hyperechoic tissues, which can be misjudged as true signals on power Doppler US.

Influence of instrument settings on flow signal and background noise in power Doppler US. An experimental study using a flow phantom with hyperechoic background.

OBJECTIVE: To determine the influence of various power Doppler instrument settings on intensities of flow signal and background noise in flow with a tissue-equivalent phantom. METHODS: Power Doppler images were obtained with changing wall filter level (low, medium, high, and maximum), pulse repetition frequency (PRF; 500, 700, 1000, 1500, 3000, and 6000 Hz), and Doppler gain (60%, 70%, 80%, 90%, and 100%) at different flow velocities (13.3, 26.5, and 49.8 cm/sec). To make a quantitative comparison of different settings, the authors measured the intensities of flow signal and background noise in obtained power Doppler images using the scanner and a computer program, calculated signal-to-noise difference (SND; intensity of flow signal--intensity of background noise), and evaluated the relation between SND and power Doppler settings. RESULTS: The intensities of flow signal and background noise were proportional to flow velocity and power Doppler gain but were inversely proportional to PRF and wall filter level. At constant wall filter level (medium), changes of PRF and Doppler gain to the same directions resulted in a high SND. At constant PRF (1000 Hz), changes of wall filter and Doppler gain to the same directions also resulted in a high SND. However, at constant Doppler gain (80%), a high SND was obtained with changing wall filter level and PRF to the opposite directions. CONCLUSIONS: Three Doppler instrument settings--wall filter level, pulse repetition frequency, and Doppler gain--have reciprocal influences on SND.