[Preliminary outcomes of neoadjuvant chemoimmunotherapy combined with transoral robotic surgery for locally advanced oropharyngeal squamous cell carcinoma].

Objective: To evaluate the efficacy of neoadjuvant chemoimmunotherapy (NACI) combined with transoral robotic surgery (TORS) in the treatment of locally advanced oropharyngeal squamous cell carcinoma (OPSCC). Methods: This was a retrospective study of 15 patients with locally advanced OPSCC who underwent TORS after neoadjuvant therapy (NAT) at the Department of Otolaryngology-Head and Neck Surgery of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2019 to February 2023. There were 12 males and 3 females, aged 31 to 74 years. Twelve cases were tonsil cancer, and 3 cases were tongue base cancer. There were 11 cases in stage Ⅲ and 4 cases in stage Ⅳ. Two patients received neoadjuvant chemotherapy and 13 patients received NACI, with 2 to 3 cycles, and all patients underwent TORS after multidisciplinary team consultation. The clinicopathological characteristics, surgical outcomes, and oncological results were summarized. Results: All surgeries were successfully completed with negative surgical margins, and no case was required conversion surgery. All patients were fed via nasogastric tubes postoperatively, with a median gastric tube stay of 7 days (range: 2-60 days). No tracheotomy was applied. There were no major complications such as postoperative bleeding. Pathological complete response (pCR) was found in 10 cases (76.9%) among the 13 patients with NACI. The follow-up time was 21 months (range: 10-47 months), and there was no death or distant metastasis. One patient with rT0N3M0 tonsil cancer had local recurrence 5 months after surgery. The 2-year overall survival and 2-year disease-free survival were respectively 100.0% and 93.3% in the 15 patients. Conclusion: NACI combined with TORS provides a safe, effective and minimally invasive treatment for patients with locally advanced oropharyngeal squamous cell carcinoma.

[Preliminary experience of gasless transoral vestibular robotic thyroidectomy].

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.

[Preliminary experience of robotic lateral neck dissection via combined axillary-retroauricular approach for N1b papillary thyroid carcinoma].

Objective: To evaluate the feasibility, safety, and short-term efficacy of robotic lateral neck dissection via combined axillary-retroauricular approach for N1b papillary thyroid carcinoma (PTC). Methods: Thirty patients with cT1-2N1bM0 PTC who received robotic lateral neck dissection via combined axillary-retroauricular approach were included in the Department of Otorhinolaryngology of Sun Yat-sen Memorial Hospital from December 2016 to December 2020. There were 10 males and 20 females, with a median age of 34.5 years and a median body mass index of 25.55 kg/m2. The clinical, surgical, complications, pathology and follow-up data were analysed with SPSS 25.0 software package. Results: The median operative time of 30 patients was 255.50 min, the median operative blood loss was 69.00 ml, and the median postoperative hospital stay was 6.00 days. The incidence of postoperative temporary recurrent laryngeal nerve paralysis was 3.33% (1/30), temporary hypoparathyroidism was 16.67%(5/30), temporary accessory nerve injury was 3.33% (1/30), hematoma was 3.33% (1/30) and chylous leakage was 3.33% (1/30). The median visual analogue scale (VAS) score was 8.00, and the follow-up time was 13-38 months, with a median of 25.5 months. One case showed cervical lymph node recurrence 14 months after surgery. The most recent dynamic recurrence risk stratification showed 21 patients (70.00%) had excellent responses. Conclusions: Robotic lateral neck dissection via combined axillary-retroauricular approach for unilateral cN1b PTC is safe, feasible and aesthetic. The short-term efficacy and dynamic recurrence risk stratification results of short-term follow-up are satisfactory. It can provide a surgical option for cN1b PTC patients.

[Transoral robotic nasopharyngectomy for local recurrent nasopharyngeal carcinoma].

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.

Protein kinase C signalling involved in prothoracicotropic hormone-stimulated prothoracic glands in the silkworm, Bombyx mori.

In the present study, the participation of protein kinase C (PKC) signalling in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37-kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37-kDa protein phosphorylation. PTTH-stimulated phosphorylation of the 37-kDa protein was markedly attenuated in the absence of Ca2+ . The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH-stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC-dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone and diphenylene iodonium) inhibited PTTH-stimulated phosphorylation of the 37-kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C or rottlerin) reduced PTTH-stimulated phosphorylation of the 37-kDa protein. PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signalling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signalling is involved in ecdysteroid secretion in Bombyx PGs.

Long noncoding RNA GAS5 attenuates cardiac fibroblast proliferation in atrial fibrillation via repressing ALK5.

OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have caught more attention for their role in the progression of many diseases. Among them, lncRNA GAS5 (Growth Inhibition Specificity 5) was studied in this research to identify how it affects the progression of atrial fibrillation (AF). PATIENTS AND METHODS: In 40 patients with AF and 30 patients with sinus rhythm (SR), the GAS5 expression of the right atrial appendage (RAA) tissues was detected by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, the cell proliferation assay was conducted in AC16 cells transfected with GAS5 inhibitor and mimics, respectively. Furthermore, the qRT-PCR was performed to uncover the mechanism. RESULTS: In the research, the expression of GAS5 in RAA tissues was decreased significantly in AF patients than that in SR ones. Moreover, overexpression of GAS5 inhibited cell growth in AC16 cells, while knockdown of GAS5 promoted cell growth in AC16 cells. In addition, further experiments revealed that ALK5 was a target of GAS5 and its expression in AF tissues negatively correlated to GAS5 expression. CONCLUSIONS: These results indicate that GAS5 could inhibit cell proliferation of AF via suppressing ALK5, which may offer a new vision for interpreting the mechanism of AF development.

[Gasless endoscopic selective lateral neck dissection via an anterior chest approach for papillary thyroid carcinomas].

Objective: To assess the safety and curative effect of gasless endoscopic selective lateral neck dissection (GESLND) via an anterior chest approach for papillary thyroid carcinoma (PTC). Methods: Eighteen patients with PTC(T1-2N1bM0, size<3.0 cm), having GESLND via an anterior chest approach, were included from November 2008 to December 2016. Results: GESLND via an anterior chest approach was successfully performed in all 18 PTC patients (seven male and eleven female) with 83.3% of T1 and 16.7% of T2. The mean operative time of selective lateral neck dissection was 73 min (range 51-92 min). The mean of intraoperative bleeding was 61.1 ml (range 30-120 ml). No major complications occurred except one transient hypoparathyroidism. No residual thyroid glands were detected on ultrasonography and thyroglobulin was(0.73±0.16)ng/ml three months postoperatively. The median of follow-up was 54.5 months (range 6-104 months). No recurrence disease was observed in any patient on ultrasonography, computer tomography, thyroglobulin or selective iodine-131 scan during the follow-up period. The cosmetic result and functional preservation was excellent, when the assessments were performed three months postoperatively. Conclusion: GESLND via an anterior chest approach is feasible and safe for selected PTCs, with superior appearance.

[The significance of preservation of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach].

Objective: To evaluate the significance for the preservation of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach. Methods: We retrospectively evaluated 168 patients who underwent unilateral endoscopic thyroidectomy via gasless anterior chest approach, with preservation of the medial branch of the supraclavicular nerve in 110 patients and not in other 58 patients. Semmes-Weinstein monofilament (SWM) test and a visual analogue scale (VAS) were used to assess the recovery of sensation in anterior chest within 1-12 months postoperatively. Difference in the scores of SWM or VAS between groups was tested with Mann-Whitney U test, and the rates of SWM and VAS scores returning to normal levels in individual periods after surgery was compared with Chi-square test. Results: The preserved group showed more favorable results than the non-preserved group in both SMW and VAS scores. Compared to control group, SWM score in preserved group possessed a higher rate recovery to normal level at any period after operation, which was close to complete normality in 7-9 months postoperatively, and SWM score in non-preserved group was still partially normal in 10-12 months from surgery. Preferable results for VAS were also found in the preserved group, except no significant difference in VAS between groups in1-3 months or 10-12 months after operation. Conclusion: Preservation of the medial branch of the supraclavicular nerve in endoscopic thyroidectomy via gasless anterior chest approach can improve sensation recovery in anterior chest, thus improving postoperative quality of life of patients.

Comparison of two stroke volume variation-based goal-directed fluid therapies for supratentorial brain tumour resection: a randomized controlled trial.

Background: The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection. Methods: A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100ß, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared. Results: Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg-1 h-1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min-1 m-2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P<0.05). Conclusions: During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol. Clinical trial registration: NCT02113358.

Automatic methods for alveolar bone loss degree measurement in periodontitis periapical radiographs.

BACKGROUND AND OBJECTIVE: Periodontitis involves progressive loss of alveolar bone around the teeth. Hence, automatic alveolar bone loss measurement in periapical radiographs can assist dentists in diagnosing such disease. In this paper, we propose an automatic length-based alveolar bone loss measurement system with emphasis on a cementoenamel junction (CEJ) localization method: CEJ_LG. METHOD: The bone loss measurement system first adopts the methods TSLS and ABLifBm, which we presented previously, to extract teeth contours and bone loss areas from periodontitis radiograph images. It then applies the proposed methods to locate the positions of CEJ, alveolar crest (ALC), and apex of tooth root (APEX), respectively. Finally the system computes the ratio of the distance between the positions of CEJ and ALC to the distance between the positions of CEJ and APEX as the degree of bone loss for that tooth. The method CEJ_LG first obtains the gradient of the tooth image then detects the border between the lower enamel and dentin (EDB) from the gradient image. Finally, the method identifies a point on the tooth contour that is horizontally closest to the EDB. RESULTS: Experimental results on 18 tooth images segmented from 12 periodontitis periapical radiographs, including 8 views of upper-jaw teeth and 10 views of lower-jaw teeth, show that 53% of the localized CEJs are within 3 pixels deviation (∼ 0.15 mm) from the positions marked by dentists and 90% have deviation less than 9 pixels (∼ 0.44 mm). For degree of alveolar bone loss, more than half of the measurements using our system have deviation less than 10% from the ground truth, and all measurements using our system are within 25% deviation from the ground truth. CONCLUSION: Our results suggest that the proposed automatic system can effectively estimate degree of horizontal alveolar bone loss in periodontitis radiograph images. We believe that our proposed system, if implemented in routine clinical practice, can serve as a valuable tool for early and accurate diagnosis of alveolar bone loss in periodontal diseases and also for assessing the status of alveolar bone following various types of non surgical and surgical and regenerative therapy. For overall system improvement, a more objective comparison by using transgingival bone measurement with a periodontal probe as the ground truth and enhancing the localization algorithms of these three critical points are the two major tasks.

Alveolar bone-loss area localization in periodontitis radiographs based on threshold segmentation with a hybrid feature fused of intensity and the H-value of fractional Brownian motion model.

BACKGROUND AND OBJECTIVE: Periodontitis involves progressive loss of alveolar bone around the teeth. Hence, automatic alveolar bone-loss (ABL) measurement in periapical radiographs can assist dentists in diagnosing such disease. In this paper, we propose an effective method for ABL area localization and denote it as ABLIfBm. METHOD: ABLIfBm is a threshold segmentation method that uses a hybrid feature fused of both intensity and texture measured by the H-value of fractional Brownian motion (fBm) model, where the H-value is the Hurst coefficient in the expectation function of a fBm curve (intensity change) and is directly related to the value of fractal dimension. Adopting leave-one-out cross validation training and testing mechanism, ABLIfBm trains weights for both features using Bayesian classifier and transforms the radiograph image into a feature image obtained from a weighted average of both features. Finally, by Otsu's thresholding, it segments the feature image into normal and bone-loss regions. RESULTS: Experimental results on 31 periodontitis radiograph images in terms of mean true positive fraction and false positive fraction are about 92.5% and 14.0%, respectively, where the ground truth is provided by a dentist. The results also demonstrate that ABLIfBm outperforms (a) the threshold segmentation method using either feature alone or a weighted average of the same two features but with weights trained differently; (b) a level set segmentation method presented earlier in literature; and (c) segmentation methods based on Bayesian, K-NN, or SVM classifier using the same two features. CONCLUSION: Our results suggest that the proposed method can effectively localize alveolar bone-loss areas in periodontitis radiograph images and hence would be useful for dentists in evaluating degree of bone-loss for periodontitis patients.

Teeth segmentation of dental periapical radiographs based on local singularity analysis.

Teeth segmentation for periapical raidographs is one of the most critical tasks for effective periapical lesion or periodontitis detection, as both types of anomalies usually occur around tooth boundaries and dental radiographs are often subject to noise, low contrast, and uneven illumination. In this paper, we propose an effective scheme to segment each tooth in periapical radiographs. The method consists of four stages: image enhancement using adaptive power law transformation, local singularity analysis using Hölder exponent, tooth recognition using Otsu's thresholding and connected component analysis, and tooth delineation using snake boundary tracking and morphological operations. Experimental results of 28 periapical radiographs containing 106 teeth in total and 75 useful for dental examination demonstrate that 105 teeth are successfully isolated and segmented, and the overall mean segmentation accuracy of all 75 useful teeth in terms of (TP, FP) is (0.8959, 0.0093) with standard deviation (0.0737, 0.0096), respectively.

Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 µM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 µM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 µM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 µM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 µM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 µM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts.

Macrophages and control of granulomatous inflammation in tuberculosis.

The granuloma that forms in response to Mycobacterium tuberculosis must be carefully balanced in terms of immune responses to provide sufficient immune cell activation to inhibit the growth of the bacilli, yet modulate the inflammation to prevent pathology. There are likely many scenarios by which this balance can be reached, given the complexity of the immune responses induced by M. tuberculosis. In this review, we focus on the key role of the macrophage in balancing inflammation in the granuloma.

Effect of ropivacaine on endothelium-dependent phenylephrine-induced contraction in guinea pig aorta.

BACKGROUND: Previous studies have shown that ropivacaine has biphasic vascular effects, causing vasoconstriction at low concentrations and vasorelaxation at high concentrations. This study was designed to examine the role of the endothelium during accidental intravascular absorption of ropivacaine, and to elucidate the mechanisms responsible. METHODS: Isolated guinea pig aortic rings were suspended for isometric tension recording. The effects of ropivacaine on endothelium-intact and endothelium-denuded aortic rings were assessed. Endothelium-intact aortic rings were pre-contracted with phenylephrine before being exposed to ropivacaine and acetylcholine, in order to generate and compare concentration-response curves. In the absence and presence of yohimbine, propranolol, atropine, indometacin, N(G)-nitro-l-arginine methyl ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue, the contractile response induced by ropivacaine was assessed on endothelium-intact aortic rings pre-contracted with phenylephrine. RESULTS: Ropivacaine (3 x 10(-4) to 10(-2) mol/l) produced vasoconstriction in endothelium-denuded aortic rings, whereas no such response was observed in aortic rings with intact endothelium. In phenylephrine pre-contracted intact aortic rings, ropivacaine induced a greater degree of vasorelaxation than did acetylcholine. Yohimbine, propranolol and atropine all failed to affect the relaxation responses induced by ropivacaine. However, pre-treatment with indometacin (cyclo-oxygenase inhibitor), l-NAME (nitric oxide synthase inhibitor), methylene blue (soluble guanylyl cyclase inhibitor) or ODQ (soluble guanylyl cyclase inhibitor), significantly decreased the ropivacaine-induced relaxation of endothelium-intact aortic rings (3 x 10(-4) to 10(-2) mol/l). CONCLUSIONS: Ropivacaine elicits an endothelium-dependent vasorelaxation in phenylephrine pre-contracted aortic rings via the nitric oxide-cyclic guanosine 3',5'-monophosphate pathway and the prostaglandin system.

Cocaine elicits action potential bursts in a central snail neuron: the role of delayed rectifying K+ current.

The effects of cocaine were studied in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage-clamp method. The RP4 neuron generated spontaneous action potentials and bath application of cocaine (0.3-1 mM) reversibly elicited action potential bursts of the central RP4 neuron in a concentration-dependent manner. The action potential bursts were not blocked when neurons were immersed in high-Mg(2+)solution, Ca(2+)-free solution, nor after continuous perfusion with atropine, d-tubocurarine, propranolol, prazosin, haloperidol, or sulpiride. Similarly, the action potential bursts were not abolished by pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride, (9S,10S,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid hexyl ester or anisomycin. Injection of hyperpolarizing current at an intensity of greater than 2 nA effectively suppressed the cocaine-elicited action potential bursts and no postsynaptic potentials were observed under these conditions. These results suggest that the generation of action potential bursts elicited by cocaine was not due to (1) the synaptic effects of neurotransmitters, (2) the cholinergic, adrenergic or dopaminergic receptors of the excitable membrane, or (3) the cAMP second messengers and new protein synthesis of the RP4 neuron. Notably, the induction of action potential bursts was blocked by pretreatment with 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione. Voltage-clamp studies conducted on the RP4 neuron revealed that cocaine at 0.3 mM decreased (1) the Ca(2+) current, (2) the delayed rectifying K(+) current, (3) the fast-inactivating K(+) current and (4) the Ca(2+)-activated K(+) current, but had no remarkable effects on the Na(+) current. Perfusion with Ca(2+)-free solution, which may abolish the Ca(2+) current and Ca(2+)-activated K(+) current, did not cause any bursts of action potentials in control RP4 neurons. Application of 4-aminopyridine, an inhibitor of fast-inactivating K(+) current, and paxilline, an inhibitor of Ca(2+)-activated K(+) current, failed to elicit action potential bursts, whereas tetraethylammonium chloride, a blocker of Ca(2+)-activated K(+) current and delayed rectifying K(+) current, and tacrine, an inhibitor of delayed rectifying K(+) current, successfully elicited action potential bursts. Further, while 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione did not affect the delayed rectifying K(+) current of the RP4 neuron, 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione decreased the inhibitory effect of cocaine on the delayed rectifying K(+) current. It is concluded that cocaine elicits action potential bursts in the central snail RP4 neuron and that the effect is closely related to the inhibitory effects on the delayed rectifying K(+) current.

The effects of continuous epidural analgesia on Doppler velocimetry of uterine arteries during different periods of labour analgesia.

BACKGROUND: The transient effects of epidural bupivacaine 0.25-0.5% on the Doppler velocimetry of umbilical and uterine arteries had been reported, but the effects of continuous lower dose epidural bupivacaine (0.05-0.1%) infusion for labour analgesia have never been reported. In this study, we evaluated the effects of continuous epidural bupivacaine 0.075% on the Doppler velocimetry of uterine arteries. METHODS: Twenty pregnant women for labour analgesia received continuous epidural bupivacaine 0.075% infusion. We used a 4-MHz continuous-wave Doppler probe (Multigon 500A) with a 200 Hz thump filter to detect uterine blood flow velocity. We recorded the velocimetry data for uterine relaxation and contraction during five time periods: pre-epidural insertion, 1, 2, and 4 h post-epidural infusion, and after delivery of fetus. RESULTS: Our data showed that the velocimetric indices of uterine vascular resistance were significantly increased 1, 2, and 4 h after epidural infusion when compared with the pre-epidural level; these returned to the baseline after delivery. CONCLUSION: Continuous epidural analgesia with bupivacaine 0.075% increases the resistance of uterine artery and therefore possibly reduces the uterine blood flow.

Method for producing coded micro-carrier and test method by using a novel type biochip.

This paper provides a method for producing a novel type coded micro-carrier. A simple and cost effective solution for bio-molecule applications was developed. Application relevant items such as manufacture process, biospecific interaction, and analysis method are discussed. For low cost fabrication, the use of LIGA-like process is suggested. LIGA-like process is used as a dry patterning process in which an intense beam of light from an excimer laser is used to pattern a material directly. This process has found extensive application in the microelectronics industry for patterning of polymer materials. The use of LIGA-like techniques offers two attractive features: first, we can cut the polymer into many tiny micro-carriers with micrometer precision. Second, LIGA-like process allows to encode with high precision spatial information onto the micro-carrier that can be used in the identification of the bio-molecule. This paper gives a description of the basic idea, describes the fabrication of the novel micro-carrier that we called "coded micro-carrier," and of the image processing algorithms used for the analysis of bio-molecules. This study also provides a test method for identifying a bio-molecule, which includes mixing several coded micro-carriers with the hybridized unknown bio-molecules; and identifying the codes on the micro-carrier via image recognition system. The numbers and types of the known micro-carrier can be flexibly adjusted according to the number of tested bio-molecules.

BK virus infection in renal transplant recipients.

BK virus (BKV) is increasingly being recognized as an important pathogen among renal transplant recipients. To date, only limited information is known about BKV infections in this population; definitive data regarding the epidemiology, diagnosis, treatment, and outcome of BKV infection are lacking. Therefore, further investigations are needed. This article reviews our current understanding of BKV infections among renal transplant patients.