Sedation with propofol and isoflurane differs in terms of microcirculatory parameters: A randomized animal study using dorsal skinfold chamber mouse model.

OBJECTIVE: This study aimed to explore the effects of sedative doses of propofol and isoflurane on microcirculation in septic mice compared to controls. Isoflurane, known for its potential as a sedation drug in bedside applications, lacks clarity regarding its impact on the microcirculation system. The hypothesis was that propofol would exert a more pronounced influence on the microvascular flow index, particularly amplified in septic conditions. MATERIAL AND METHODS: Randomized study was conducted from December 2020 to October 2021 involved 60 BALB/c mice, with 52 mice analyzed. Dorsal skinfold chambers were implanted, followed by intraperitoneal injections of either sterile 0.9 % saline or lipopolysaccharide for the control and sepsis groups, respectively. Both groups received propofol or isoflurane treatment for 120 min. Microcirculatory parameters were obtained via incident dark-field microscopy videos, along with the mean blood pressure and heart rate at three time points: before sedation (T0), 30 min after sedation (T30), and 120 min after sedation (T120). Endothelial glycocalyx thickness and syndecan-1 concentration were also analyzed. RESULTS: In healthy controls, both anesthetics reduced blood pressure. However, propofol maintained microvascular flow, differing significantly from isoflurane at T120 (propofol, 2.8 ± 0.3 vs. isoflurane, 1.6 ± 0.9; P < 0.001). In the sepsis group, a similar pattern occurred at T120 without statistical significance (propofol, 1.8 ± 1.1 vs. isoflurane, 1.2 ± 0.7; P = 0.023). Syndecan-1 levels did not differ between agents, but glycocalyx thickness index was significantly lower in the isoflurane-sepsis group than propofol (P = 0.001). CONCLUSIONS: Propofol potentially offers protective action against microvascular flow deterioration compared to isoflurane, observed in control mice. Furthermore, a lower degree of sepsis-induced glycocalyx degradation was evident with propofol compared to isoflurane.

Comparison between conventional-dose and high-dose rocuronium use in general anesthesia for Cesarean section.

Background: There have been few studies comparing the effects of high- and low-dose rocuronium during cesarean section by directly measuring the concentration. Therefore, we conducted a study to examine the blood concentrations and clinical effects of both doses of rocuronium on mothers and fetuses. Methods: Eighteen patients were randomly assigned to two groups: C Group (0.6 mg/kg), and H Group, (1.0 mg/kg). The primary outcome was the comparison of umbilical vein rocuronium concentration between two groups. We assessed ease of intubation, time from rocuronium administration to some TOF points, post-anesthesia care unit (PACU) stay time, infused remifentanil dose, maternal rocuronium concentration, and Apgar scores. Results: No differences were observed in demographic data, ease of intubation, PACU stay time, 1 min Apgar scores, umbilical venous blood gas analysis between both groups. However, the time from rocuronium administration to T3 disappearance was shorter (p=0.009) and time to T1 and T2 reappearance were longer (p=0.003, p=0.009) in H group than that in C group. The administered remifentanil dose (p=0.042) was lower in the H group than in the C group. Rocuronium concentrations in the umbilical vein (p=0.004) and maternal vein before cord clamping (p=0.002) and at discharge (p<0.001) were also found to be higher in the H group than in the C group. Conclusions: We observed no prolongation of PACU stay, and no differences in Apgar scores in H group compared to C group. It suggests that 1.0 mg/kg of rocuronium has no negative effects on the fetus and mother in cesarean section.

A Study of 57 Patients with Prostate Cancer to Compare Outcomes of Estimated Blood Loss and Postoperative Pain Between Robot-Assisted Laparoscopic Radical Prostatectomy and Standard Laparoscopic Radical Prostatectomy.

BACKGROUND Robot-assisted radical prostatectomy (RARP) is becoming an increasingly common method for treatment of prostate cancer. This study aimed to compare outcomes of estimated blood loss and postoperative pain, determined by patient-controlled analgesia (PCA), between RARP and standard laparoscopic radical -prostatectomy (LRP). MATERIAL AND METHODS We enrolled 57 patients who had localized prostate cancer (28 patients in RARP, 29 patients in LRP). Primary outcomes were estimated blood loss (EBL) measured by gravimetric method for gauze and visual estimation for suction bottle, and PCA bolus count that the bolus doses were injected at the 1st, the 6th, the 24th, and the 48th hour after the operation. We recorded anesthesia and operation time, pneumoperitoneum duration, vital signs, fluid volume, and remifentanil use. Using the numeric rating scale (NRS), adverse effects were checked at the 1st, the 6th, the 24th, and the 48th hour and patient satisfaction was assessed at the 48th hour after the operation. RESULTS Anesthesia time, operation time, and gas insufflation time were longer (P=0.001, P=0.003, P=0.021), and patient-controlled analgesia (PCA) bolus counts at the 1st hour after the operation and volumes of administered crystalloid and remifentanil were higher in the RARP group than in the LRP group (P=0.013, P=0.011, P=0.031). There were no significant differences in EBL. CONCLUSIONS The RARP group required longer anesthetic time and more analgesics during the acute postoperative period compared to the LRP group. Regarding anesthesia, LRP is as good a surgical procedure as RARP until the operation time and the number of ports are reduced.

Ultrasonographic Carotid Artery Flow Measurements as Predictors of Spinal Anesthesia-Induced Hypotension in Elderly Patients: A Prospective Observational Study.

BACKGROUND In elderly patients, spinal anesthesia-induced hypotension (SAH) can be frequently caused by reduced preload and stiff ventricles. The primary purpose of this study was to investigate the ability of ultrasonographic carotid artery flow measurements during the passive leg raise (PLR) test to predict SAH in elderly patients. The correlation between preoperative transthoracic echocardiography (TTE) measurements and SAH was also investigated. MATERIAL AND METHODS The patients aged over 65 years scheduled for elective surgery under spinal anesthesia were recruited. Preoperative TTE was performed in all patients. Corrected carotid flow time and carotid blood flow were measured in the supine, semirecumbent, and PLR positions. Ultrasonographic carotid artery flow and preoperative TTE measurements were compared between patients who developed SAH and those who did not. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to test the association with SAH. RESULTS SAH occurred in 17 of 50 patients. Carotid blood flow in the semirecumbent position and preoperative mitral inflow E velocity could predict SAH, showing an area under the ROC curve of 0.754 (95% CI, 0.612-0.865) and 0.775 (95% CI, 0.634-0.881), respectively. However, according to the multivariate analysis, the independent risk factor for SAH was mitral inflow E velocity (OR 0.918, 95% CI 0.858-0.982, P=0.013). CONCLUSIONS In elderly patients, ultrasonographic carotid artery flow measurements failed to predict the occurrence of SAH. Only preoperative mitral inflow E velocity of TTE was selected as an independent risk factor for SAH.

Spatiotemporal organization of enteroendocrine peptide expression in Drosophila.

The digestion of food and absorption of nutrients occurs in the gut. The nutritional value of food and its nutrients is detected by enteroendocrine cells, and peptide hormones produced by the enteroendocrine cells are thought to be involved in metabolic homeostasis, but the specific mechanisms are still elusive. The enteroendocrine cells are scattered over the entire gastrointestinal tract and can be classified according to the hormones they produce. We followed the changes in combinatorial expression of regulatory peptides in the enteroendocrine cells during metamorphosis from the larva to the adult fruit fly, and re-confirmed the diverse composition of enteroendocrine cell populations. Drosophila enteroendocrine cells appear to differentially regulate peptide expression spatially and temporally depending on midgut region and developmental stage. In the late pupa, Notch activity is known to determine which peptides are expressed in mature enteroendocrine cells of the posterior midgut, and we found that the loss of Notch activity in the anterior midgut results in classes of enteroendocrine cells distinct from the posterior midgut. These results suggest that enteroendocrine cells that populate the fly midgut can differentiate into distinct subtypes that express different combinations of peptides, which likely leads to functional variety depending on specific needs.

Identification and characterization of GAL4 drivers that mark distinct cell types and regions in the Drosophila adult gut.

The gastrointestinal tract in the adult Drosophila serves as a model system for exploring the mechanisms underlying digestion, absorption and excretion, stem cell plasticity, and inter-organ communication, particularly through the gut-brain axis. It is also useful for studying the cellular and adaptive responses to dietary changes, alterations in microbiota and immunity, and systematic and endocrine signals. Despite the various cell types and distinct regions in the gastrointestinal tract, few tools are available to target and manipulate the activity of each cell type and region, and their gene expression. Here, we report 353 GAL4 lines and several split-GAL4 lines that are expressed in enteric neurons (ENs), progenitors (ISCs and EBs), enterocytes (ECs), enteroendocrine cells (EEs), or/and other cell types that are yet to be identified in distinct regions of the gut. We had initially collected approximately 600 GAL4 lines that may be expressed in the gut based on RNA sequencing data, and then crossed them to UAS-GFP to perform immunohistochemistry to identify those that are expressed selectively in the gut. The cell types and regional expression patterns that are associated with the entire set of GAL4 drivers and split-GAL4 combinations are annotated online at http://kdrc.kr/index.php (K-Gut Project). This GAL4 resource can be used to target specific populations of distinct cell types in the fly gut, and therefore, should permit a more precise investigation of gut cells that regulate important biological processes.

Microvascular Reactivity Measured by Dynamic Near-infrared Spectroscopy Following Induction of General Anesthesia in Healthy Patients: Observation of Age-related Change.

Background: The purpose of this study was to investigate the effect of general anesthesia on microvascular reactivity and tissue oxygen saturation (StO2) using near-infrared spectroscopy in conjunction with vascular occlusion tests (VOT). Age-related changes of microvascular reactivity, that is, the capacity of capillary recruitment, were examined. Methods: This prospective observational study was performed on 60 patients without comorbidities who underwent elective surgery under general anesthesia. Baseline StO2 on thenar eminence, hemodynamics, and laboratory profile were monitored before (T0) and 30 min after general anesthesia (T1). During VOT, occlusion slope representing oxygen consumption of muscle and recovery slope representing microvascular reactivity were also collected at T0 and T1. Results: Baseline StO2 and minimum / maximum StO2 during VOT increased under general anesthesia. Occlusion slope decreased while the recovery slope increased under general anesthesia. To observe aging effect, Receiver operating characteristic analysis was performed and age less than 65 years old showed a fair performance in predicting the increase of microvascular reactivity after the induction of anesthesia (AUC 0.733, 95% CI 0.594-0.845, P= 0.003). For age-related analyses, 27 patients of younger group (< 65 years) and 26 patients of older group (≥ 65 years) were divided. Recovery slope significantly increased under general anesthesia in younger group (2.44 [1.91-2.81] % ∙ sec-1 at T0 and 3.59 [2.58-3.51] % ∙ sec-1 at T1, P <0.001), but not in older group (2.61 [2.21-3.20] % ∙ sec-1 at T0, 2.63 [1.90-3.60] % ∙ sec-1 at T1, P = 0.949). Conclusions: General anesthesia could improve StO2 through increase of microvascular reactivity and decrease of tissue metabolism. However, microvascular reactivity to capillary recruitment under general anesthesia significantly improves in younger patients, not in older patients.

Drosophila Gr64e mediates fatty acid sensing via the phospholipase C pathway.

Animals use taste to sample and ingest essential nutrients for survival. Free fatty acids (FAs) are energy-rich nutrients that contribute to various cellular functions. Recent evidence suggests FAs are detected through the gustatory system to promote feeding. In Drosophila, phospholipase C (PLC) signaling in sweet-sensing cells is required for FA detection but other signaling molecules are unknown. Here, we show Gr64e is required for the behavioral and electrophysiological responses to FAs. GR64e and TRPA1 are interchangeable when they act downstream of PLC: TRPA1 can substitute for GR64e in FA but not glycerol sensing, and GR64e can substitute for TRPA1 in aristolochic acid but not N-methylmaleimide sensing. In contrast to its role in FA sensing, GR64e functions as a ligand-gated ion channel for glycerol detection. Our results identify a novel FA transduction molecule and reveal that Drosophila Grs can act via distinct molecular mechanisms depending on context.

Role of Sevoflurane on Natural Killer Group 2, Member D-Mediated Immune Response in Non-Small-Cell Lung Cancer: An In Vitro Study.

BACKGROUND The purpose of this study was to investigate the effects of sevoflurane on cancer immunosurveillance and metastasis in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS NCI-H23 cells, a human NSCLC cell line, were incubated with or without sevoflurane at the concentrations of 0, 12.5, 25, 50, 100, and 200 µM for 6 h. Cell viability, the expression of natural killer group 2, member D ligands (NKG2D ligands: UL16-binding proteins 1-3 [ULBP1-3] and major histocompatibility complex class I chain-related molecules A/B [MICA/B]), the expression of matrix metalloproteinases (MMPs), NK cell-mediated cytotoxicity, and cancer cell migration were measured. RESULTS At 12.5, 25, 50, and 100 µM, sevoflurane increased the expression of NKG2D ligands (ULBP2-3 and MICA, ULBP1-3, ULBP1-3, and ULBP1, respectively). Sevoflurane decreased the expression of NKG2D ligands at 200 µM (MICA/B). NK cell-mediated lysis of NCI-H23 cells at 200 µM sevoflurane was significantly reduced compared with the control (P=0.025; target cell: effect cell=1: 10). Sevoflurane increased the expression of MMP-1, -2, and -9 and increased cell migration in NCI-H23 cells at 50, 100, and 200 µM (P=0.001, 0.035, and 0.039, respectively, compared with the control after 18 h of wound formation). CONCLUSIONS Sevoflurane could suppress NKG2D-mediated NK cell cytotoxicity and increased expression of MMPs and migration in NCI-H23 cells. Further research is needed to determine the effects of sevoflurane on cancer immunosurveillance and metastasis in NSCLC.

TrpA1 Regulates Defecation of Food-Borne Pathogens under the Control of the Duox Pathway.

Pathogen expulsion from the gut is an important defense strategy against infection, but little is known about how interaction between the intestinal microbiome and host immunity modulates defecation. In Drosophila melanogaster, dual oxidase (Duox) kills pathogenic microbes by generating the microbicidal reactive oxygen species (ROS), hypochlorous acid (HOCl) in response to bacterially excreted uracil. The physiological function of enzymatically generated HOCl in the gut is, however, unknown aside from its anti-microbial activity. Drosophila TRPA1 is an evolutionarily conserved receptor for reactive chemicals like HOCl, but a role for this molecule in mediating responses to gut microbial content has not been described. Here we identify a molecular mechanism through which bacteria-produced uracil facilitates pathogen-clearing defecation. Ingestion of uracil increases defecation frequency, requiring the Duox pathway and TrpA1. The TrpA1(A) transcript spliced with exon10b (TrpA1(A)10b) that is present in a subset of midgut enteroendocrine cells (EECs) is critical for uracil-dependent defecation. TRPA1(A)10b heterologously expressed in Xenopus oocytes is an excellent HOCl receptor characterized with elevated sensitivity and fast activation kinetics of macroscopic HOCl-evoked currents compared to those of the alternative TRPA1(A)10a isoform. Consistent with TrpA1's role in defecation, uracil-excreting Erwinia carotovora showed higher persistence in TrpA1-deficient guts. Taken together, our results propose that the uracil/Duox pathway promotes bacteria expulsion from the gut through the HOCl-sensitive receptor, TRPA1(A)10b, thereby minimizing the chances that bacteria adapt to survive host defense systems.

Propofol attenuates osteoclastogenesis by lowering RANKL/OPG ratio in mouse osteoblasts.

Bone remodeling plays an important role in the bone healing process; for example, following fracture. The relative ratio of the receptor activator of nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) controls osteoclast differentiation, thereby playing a pivotal role in the regulation of bone remodeling. Propofol, a widely used anesthetic agent in orthopedic procedures, is considered to possess potential antioxidant properties owing to its structural similarity to α-tocopherol. Antioxidants are known to enhance bone healing. Accordingly, in the present study, we aimed to investigate osteoblastic differentiation and RANKL/OPG expression following propofol administration, in order to assess the potentially beneficial effects of this drug on the bone remodeling process, using calvarial primary osteoblasts from newborn mice. Calvarial pre-osteoblast cells were cultured in media containing clinically relevant concentrations of propofol, and cytotoxicity, effects on cell proliferation, osteogenic activity, and osteoclastogenesis were examined. The present findings indicated that propofol did not exert cytotoxic effects or alter cell proliferation in primary calvarial osteoblasts. Further, propofol did not affect osteoblast differentiation. The RANKL/OPG ratio was found to be decreased following propofol administration, and osteoclastogenesis was significantly reduced, indicating that propofol attenuated the osteoclastogenesis-supporting activity of osteoblasts. The results demonstrate that propofol, at clinically relevant concentrations, exerts beneficial effects on bone remodeling by attenuating osteoclastogenesis via suppression of the RANKL/OPG expression axis.

A prospective pilotstudy comparing the anesthetic effects of an alpha-2 agonist during holmium laser resection of the prostate and transurethral resection for prostate surgery for benign prostatic hyperplasia patients using selective alpha-1 blockers.

BACKGROUND: To examine the response to an α2receptor agonist used as a sedative for patients using long-term selective α1 blockers. METHODS: Sixty-nine consecutive patients undergoing transurethral prostate resection or holmium laser resection of the prostateunder spinal anesthesia were divided into two groups; group N (n = 37), which did not receive α1 blockers, and group T (n = 32), which was administered tamsulosin for at least 1 month before the study. Bispectral index scores, Modified Observer's Assessment of Alertness/Sedation scale scores, heart rate, and mean blood pressure were obtained under sedation using dexmedetomidine for 30 min during surgery. RESULTS: The only significant difference found between the groups were mean bloodpressure 15 min after the first loading dose injection of dexmedetomidine. Differencesbetween both groupswere noted at 15 min(group T: 100.2 ± 12.9 mmHg; group N: 90.0 ± 17.5 mmHg; P = 0.08), 20 min (group T: 99.8 ± 12.3 mmHg; group N: 87.4 ± 15.0 mmHg; P < 0.00), 25 min (group T: 99.3 ± 13.4 mmHg; group N: 85.4 ± 13.8 mmHg; P < 0.00), and 30 min (group T: 98.8 ± 13.1 mmHg; group N: 84.5 ± 13.5 mmHg; P < 0.00). CONCLUSIONS: The use of α2 agonists is appropriate during surgery for benign prostatic hyperplasia patients using tamsulosin, and there is no need to alter the dose. Alertness with anesthesia involving α2 agents was maintained for patients using long-term tamsulosin and patients who did not use tamsulosin. TRIAL REGISTRATION: The study was retrospectively registered with the Clinical Research Informational Service ( KCT0002967 , July 2, 2018).

Observations on significant hemodynamic changes caused by a high concentration of epidurally administered ropivacaine: correlation and prediction study of stroke volume variation and central venous pressure in thoracic epidural anesthesia.

BACKGROUND: Thoracic epidural anesthesia (TEA) exacerbates hypotension due to peripheral vasodilator effects following the use of general anesthetics. This study aimed to compare the hemodynamic changes caused by three different concentrations of epidural ropivacaine and to evaluate the performance of the stroke-volume variation (SVV) and central venous pressure (CVP) during TEA with general anesthesia. METHODS: A total of 120 patients were administered 8 mL of ropivacaine solution via epidural injection, following randomization into one of three groups based on the concentration of ropivacaine in the study solution: 0.75%, 0.375%, or 0.2%. Hemodynamics were monitored for 30 min after loading. We analyzed the hemodynamic changes in the subgroups according to an age cutoff of 60 years. Receiver operating characteristic (ROC) analysis was performed to characterize the relationship of the SVV, CVP, and a 20% decrease in the mean arterial pressure (MAP) following TEA. RESULTS: Data from 109 patients were analyzed. MAP and systemic vascular resistance index were significantly decreased, and SVV was significantly increased after epidural loading only in the 0.75% ropivacaine group. There was a significant difference in hemodynamics between young and elderly subgroups in the 0.75% ropivacaine group. SVV showed a negative correlation with MAP, whereas CVP showed no correlation. The ROC analysis of SVV demonstrated a weak predictive ability of a 20% decrease in MAP at 10 min after the loading dose, with an area-under-the-curve of 0.687 and a 9.5% optimal cutoff value (sensitivity, 60.6%; specificity, 68.9%). CONCLUSIONS: A high concentration of ropivacaine through TEA caused a significant decrease in the systemic vascular resistance and blood pressure. More significant decreases were shown in the elderly patients. Though the change of SVV showed a negative correlation with hypotension and indicated functional hypovolemia after TEA, the predictability was limited. CLINICAL TRIALS REGISTRATION: Number: NCT01559285 , date: January 24, 2013.

Effect of sensor location on regional cerebral oxygen saturation measured by INVOS 5100 in on-pump cardiac surgery.

PURPOSE: Near-infrared spectroscopy sensors often cannot be attached at the commercially recommended locations because combined use of neurological monitoring systems is common during on-pump cardiac surgery. The primary purpose of this study was to compare the incidence of regional cerebral oxygen desaturation and regional cerebral oxygen saturation values detected using near-infrared spectroscopy between the upper and lower forehead during on-pump cardiac surgery. METHODS: A prospective observational study was conducted with 25 adult patients scheduled for elective on-pump cardiac surgery. Regional cerebral oxygen saturations at the left upper and lower forehead and other clinical measurements were monitored intraoperatively. McNemar's test was used to analyze differences in the incidence of cerebral regional oxygen desaturation between the left upper and lower forehead. Two-way repeated measures ANOVA with post hoc Bonferroni correction was used to compare the regional cerebral oxygen saturation at each time point. RESULTS: There was a significantly higher incidence of regional cerebral oxygen desaturation at the upper than lower forehead only at 1 h after initiation of aortic cross-clamping. There were significant differences between the left upper and lower regional cerebral oxygen saturation values throughout the observation period. CONCLUSION: Regional cerebral oxygen saturation was significantly lower at the upper than lower forehead during on-pump cardiac surgery. However, disagreements in detection of cerebral regional oxygen desaturation were only significant at 1 h after initiation of aortic cross-clamping. TRIAL REGISTRATION: WHO-ICTRP, Clinical Research Information Service (CRiS). ID: KCT0000971. URL: https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=3678&type=my .

Behavioral Analysis of Bitter Taste Perception in Drosophila Larvae.

Insect larvae, which recognize food sources through chemosensory cues, are a major source of global agricultural loss. Gustation is an important factor that determines feeding behavior, and the gustatory receptors (Grs) act as molecular receptors that recognize diverse chemicals in gustatory receptor neurons (GRNs). The behavior of Drosophila larvae is relatively simpler than the adult fly, and a gustatory receptor-to-neuron map was established in a previous study of the major external larval head sensory organs. Here, we extensively study the bitter taste responses of larvae using 2-choice behavioral assays. First, we tested a panel of 23 candidate bitter compounds to compare the behavioral responses of larvae and adults. We define 9 bitter compounds which elicit aversive behavior in a dose-dependent manner. A functional map of the larval GRNs was constructed with the use of Gr-GAL4 lines that drive expression of UAS-tetanus toxin and UAS-VR1 in specific gustatory neurons to identify bitter tastants-GRN combinations by suppressing and activating discrete subsets of taste neurons, respectively. Our results suggest that many gustatory neurons act cooperatively in larval bitter sensing, and that these neurons have different degrees of responsiveness to different bitter compounds.

Pyrazolodiazepine derivatives with agonist activity toward Drosophila RYamide receptor.

The neuropeptide Y (NPY)-like signaling is conserved broadly in many animal species, and implicated in diverse biological functions, particularly those associated with feeding and metabolism. In Drosophila, three G protein coupled receptors (GPCRs) are closely related to the vertebrate NPY receptors: RYamide receptor (RYa-R) CG5811, neuropeptide F receptor (NPFR) CG1147 and short neuropeptide F receptor (sNPF-R) CG7395. Here, we screened 442 compounds of the pyrazolodiazepine analogs library, and identified four synthetic small compounds that activate the RYa-R, but not other two receptors. Their maximum activity is about 40% of the endogenous ligand, Drosophila RYamide-1, indicating they are partial agonists. Structural comparisons of these agonists identified an active core structure, characterized by phenylalanine and lysine fused pyrazolodiazepine skeletons, which can be utilized as a lead structure for further development of more potent drugs active on mammalian NPYRs. Identification of small compound agonists selective on RYa-R of the genetically amenable insect model will facilitate future efforts to understand biological functions of RYa-R, a GPCR conserved in many species.

The molecular and cellular basis of taste coding in the legs of Drosophila.

To understand the principles of taste coding, it is necessary to understand the functional organization of the taste organs. Although the labellum of the Drosophila melanogaster head has been described in detail, the tarsal segments of the legs, which collectively contain more taste sensilla than the labellum, have received much less attention. We performed a systematic anatomical, physiological, and molecular analysis of the tarsal sensilla of Drosophila. We construct an anatomical map of all five tarsal segments of each female leg. The taste sensilla of the female foreleg are systematically tested with a panel of 40 diverse compounds, yielding a response matrix of ∼500 sensillum-tastant combinations. Six types of sensilla are characterized. One type was tuned remarkably broadly: it responded to 19 of 27 bitter compounds tested, as well as sugars; another type responded to neither. The midleg is similar but distinct from the foreleg. The response specificities of the tarsal sensilla differ from those of the labellum, as do n-dimensional taste spaces constructed for each organ, enhancing the capacity of the fly to encode and respond to gustatory information. We examined the expression patterns of all 68 gustatory receptors (Grs). A total of 28 Gr-GAL4 drivers are expressed in the legs. We constructed a receptor-to-sensillum map of the legs and a receptor-to-neuron map. Fourteen Gr-GAL4 drivers are expressed uniquely in the bitter-sensing neuron of the sensillum that is tuned exceptionally broadly. Integration of the molecular and physiological maps provides insight into the underlying basis of taste coding.

The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on Chemotherapy-Induced Neuropathic Pain in Rats.

BACKGROUND: Chemotherapy-induced neuropathic pain is a significant side effect of chemotherapeutic agents. Currently, there are no effective analgesics for chemotherapy-induced neuropathic pain. Rolipram is a selective phosphodiesterase 4 inhibitor, which increases intracellular cyclic AMP in nerve and immune cells. The aim of our study was to determine the analgesic effects of rolipram on paclitaxel (PAC)-induced neuropathic pain in rats. METHODS: Chemotherapy-induced neuropathic pain was produced by intraperitoneal injection of PAC on 4 alternate days in male Sprague-Dawley rats. Mechanical allodynia was measured by using von Frey filaments. RESULTS: After the rats developed PAC-induced pain behavior (such as mechanical allodynia), a single intraperitoneal injection and continuous infusion of rolipram ameliorated PAC-induced pain behavior. In addition, systemic infusion of the drug during the early phase of developing pain behavior did not prevent the development of mechanical allodynia induced by PAC. CONCLUSIONS: These results suggest that rolipram alleviated mechanical allodynia induced by PAC in rats. Thus, phosphodiesterase 4 inhibitors may prove useful in the treatment of chemotherapy-induced neuropathic pain. However, further studies are needed to clarify their effects in clinical settings.

A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery.

OBJECTIVES: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. METHODS: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. RESULTS: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46). CONCLUSION: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required.

Comparisons of recursive partitioning analysis and conventional methods for selection of uncuffed endotracheal tubes for pediatric patients.

BACKGROUND: Numerous studies have investigated the best method of selecting the appropriate size of endotracheal tube (ETT) for children. However, none of the methods or formulae for selection of ETT size have shown better prediction over another, and they have required complex formulae calculation or even use of cumbersome equipment. Recursive partitioning analysis creates a decision tree that is more likely to enable clearer and easier visualization of decision charts compared to other data mining methods. OBJECTIVES: The aim of the current study was to develop a clinically practical and intuitive chart for prediction of ETT size. METHODS: Pediatric patients aged 2-9 years undergoing general anesthesia were intubated with uncuffed ETT. The tube size was considered optimal when a tracheal leak was detected at an inflation pressure between 10 and 25 cmH2 O. The observed ETT size was compared with the predicted ETT size calculated using Cole's formula, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree structure analysis. Preference among the prediction methods was also investigated by asking physicians about their preference of methods. RESULTS: Correct prediction rates were 33.3%, 50%, 61.9%, and 59.5%, and close prediction rates were 61.9%, 83.3%, 88.1%, and 93.7% for Cole's formulae, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree model, respectively. Fourteen of 16 physicians prefer to use the easy-to-interpret tree model. CONCLUSIONS: Analysis of the tree model by recursive partitioning structure analysis accomplished a high correct and close prediction rate for selection of an appropriate ETT size. The intuitive and easy-to-interpret tree model would be a quick and helpful tool for selection of an ETT tube for pediatric patients.