[Influencing factors of futile recanalization after endovascular therapy in acute ischemic stroke patients with large vessel occlusions].

Objective: To analyze the influencing factors of futile recanalization after endovascular therapy (EVT) in acute ischemic stroke patients with large vessel occlusions (AIS-LVO). Methods: AIS-LVO patients who underwent EVT with successful recanalization between January 2019 and December 2021 in Neurovascular Center of Changhai Hospital of Naval Medical University were retrospectively selected. Modified Rankin scale (mRS) score 3 months after EVT was used as the prognostic evaluation index, and patients with mRS scores≤2 were classified as the meaningful recanalization group and mRS scores 3-6 as the futile recanalization group. The risk factors, National Institutes of Health stroke scale (NIHSS) score, Glasgow coma scale (GCS) score, Alberta Stroke Program Early CT (ASPECT) score, core infarct volume, etc. in both groups were analyzed, and the influencing factors of futile recanalization after EVT were analyzed by multivariate logistic regression. Continuous variables that do not conform to the normal distribution are represented by [M(Q1,Q3)]. Results: A total of 368 patients meeting the inclusion criteria were collected, including 228 males and 140 females, and aged 68 (61, 77) years. There are 196 patients and 172 patients in the meaningful recanalization and futile recanalization groups, respectively, with the rate of futile recanalization 3 months after EVT of 46.74% (172/368). Comparing the general information and risk factors between the two groups found that the age of patients in the futile recanalization group [71 (65, 79) years] was higher than that in the meaningful recanalization group [65 (59, 72) years]. The baseline NIHSS score [18 (14, 22)] and the rate of not achieving modified Thrombolysis in Cerebral Ischemia grade 3 (mTICI 3) reperfusion (36.1%) were higher in the futile recanalization group than those in the meaningful recanalization group [12 (7, 17) and 19.9%]. The baseline GCS score [11 (9, 13)] was lower in the futile recanalization group than that in the meaningful recanalization group [14 (11, 15)]. The core infarct volume in the futile recanalization group [28 (7, 65) ml] was larger than that in the meaningful recanalization group [6 (0, 17) ml]. The ASPECT score [7 (5, 9)] was lower in the futile recanalization group than that in the meaningful recanalization group [9 (7, 10)]. In addition, the proportion of hypertension, atrial fibrillation, general anesthesia, and symptomatic intracranial hemorrhage was higher in the futile recanalization group (all P<0.05). The time from symptom onset to puncture and from symptom onset to reperfusion was longer in the futile recanalization group (both P<0.05). There were statistically significant differences in trial of Org 10172 in acute stroke treatment (TOAST) classification and the site of occluded blood vessels between the two groups (both P<0.05). Multivariate logistic regression indicated that age ≥80 years(OR=1.935,95%CI: 1.168-3.205), baseline NIHSS score (OR=1.999,95%CI: 1.202-3.325), GCS score (OR=2.299,95%CI: 1.386-3.814), previous stroke history (OR=1.977,95%CI: 1.085-3.604), general anesthesia (OR=1.981,95%CI: 1.143-3.435), not achieving grade 3 recanalization (OR=2.846, 95%CI: 1.575-5.143), ASPECT score<6 (OR=2.616, 95%CI: 1.168-5.857), and core infarct volume>70 ml (OR=2.712, 95%CI: 1.130-6.505) were risk factors for futile recanalization. Conclusion: Age≥80 years, previous stroke history, baseline NIHSS score≥20, GCS score≤8, general anesthesia, ASPECT score<6, core infarct volume>70 ml, and failure to achieve Grade 3 recanalization are independent influencing factors for futile recanalization after endovascular therapy in AIS-LVO patients.

The clinical characteristic of alcohol-hyperlipidemia etiologically complex type of acute pancreatitis.

OBJECTIVE: The aim of our study was to elucidate the clinical characteristics of alcoholic-hyperlipidemic etiologically complex acute pancreatitis. PATIENTS AND METHODS: We reviewed complete data from 233 patients with acute pancreatitis treated in our hospital during the period January 2017-January 2022. They were divided into three groups according to etiology: alcoholic acute pancreatitis (AAP), hyperlipidemic acute pancreatitis (HLAP), and alcoholic-hyperlipidemic acute pancreatitis (AHAP). General clinical data, co-morbidities, laboratory results, imaging data, and disease severity were analyzed and compared between groups. RESULTS: The proportion of male individuals in the AHAP group was significantly higher than that in the HLAP group (p<0.001). Age of onset was lower and the number of cases with antibiotic use was higher in the AHAP group than in the AAP group (p<0.05). Additionally, the average alcohol intake each time and weekly alcohol intake were also higher in the AHAP group than in the AAP group (p<0.05). Comparison of disease severity (moderate and severe acute pancreatitis, severe acute pancreatitis, and modified computed tomography severity index score) revealed the disease condition to be more severe in the AHAP group than in the AAP and HLAP groups (p<0.05). Accordingly, patients in the AHAP group had longer hospital stays than those in the other two groups (p<0.05). There were no significant differences in alcohol consumption, severity, or length of hospital stay in the AHAP group (p>0.05). CONCLUSIONS: The clinical characteristics of patients in the AHAP, AAP and HLAP groups were different, and the patients in the AHAP group were more likely to have a moderate to severe disease course, with longer hospital stay. As a new AP classification concept, AHAP would offer high significance for diagnosis, treatment, and prognosis.

Comparison of Aspiration versus Stent Retriever Thrombectomy as the Preferred Strategy for Patients with Acute Terminal Internal Carotid Artery Occlusion: A Propensity Score Matching Analysis.

BACKGROUND AND PURPOSE: There is no consensus on endovascular treatment for terminal ICA. The purpose of this study was to evaluate the comparative safety and efficacy of preferred aspiration thrombectomy and stent retriever thrombectomy for revascularization in patients with isolated terminal ICA occlusion. MATERIALS AND METHODS: We conducted a retrospective analysis of patients with terminal ICA occlusion treated with aspiration thrombectomy or stent retriever thrombectomy in our center, from September 2013 to November 2018. To minimize the case bias, propensity score matching was performed. The primary outcomes were successful reperfusion defined by expanded TICI grades 2b-3 at the end of all endovascular procedures and puncture-to-reperfusion time. RESULTS: A total of 109 consecutive patients with terminal ICA occlusion were divided into the aspiration thrombectomy group (40 patients) and the stent retriever thrombectomy group (69 patients), and 30 patients were included in each group after propensity score matching. The proportion of complete reperfusion was significantly higher in the aspiration thrombectomy group (OR 4.75 [95% CI, 1.10-1.38]; P = .002). The median puncture-to-reperfusion time in the aspiration thrombectomy group was shorter than that in the stent retriever thrombectomy group (38 versus 69 minutes; P = .001). Fewer intracerebral hemorrhage events were recorded in the aspiration thrombectomy group (OR 0.29 [95% CI, 0.09-0.90]; P = .028). No significant differences were observed for good outcomes (OR 1.92 [95% CI, 0.86-4.25]) and mortality (OR 0.84 [95% CI, 0.29-2.44]) at 90 days. CONCLUSIONS: For the treatment of terminal ICA occlusion, aspiration thrombectomy was technically superior to stent retriever thrombectomy in the absence of a balloon guide catheter in achieving successful reperfusion with shorter puncture-to-reperfusion time and procedure-related adverse events.

Reconstruction of lymphatic vessels in the mouse tail after cupping therapy.

BACKGROUND: The aim of the study was to investigate the regulatory mechanism of local lymphatic reconstruction after cupping therapy in a mouse model. MATERIALS AND METHODS: The lymphatic reconstruction process in the mouse tail after cupping therapy as well as the expression levels of the vascular endothelial identification molecule CD34, prospero homeobox protein 1 (PROX1), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) were investigated for a duration of 4 days through immunohistochemistry experiments. RESULTS: On day 1 after cupping therapy, the CD34+ and LYVE-1+ cell densities were significantly increased, and the formed CD34+LYVE-1+ tubular structure started to express PROX1. This was followed by a decrease in both the CD34+ and LYVE-1+ stem cell densities to basal levels on the second day after cupping therapy. Both the CD34+ and LYVE-1+ cell densities subsequently increased again on the third day after cupping therapy. The increase in the LYVE-1+ density was accompanied by tubular structure formation, which is characteristic of lymphangiogenesis. In addition, the colocalisation of CD34+ and LYVE-1+ cells by immunohistochemistry suggests that the CD34+ stem cells differentiated into new lymphatic endothelial cells. CONCLUSIONS: Our findings indicate that the mechanism underlying the therapeutic effect of cupping therapy involves upregulation of vascular and lymphatic endothelial markers (CD34+, LYVE-1+, and CD34+LYVE-1+) in local tissues, which in turn promotes local new lymphatic vessel formation through the expression of PROX1.

On the accuracy of optically tracked transducers for image-guided transcranial ultrasound.

PURPOSE: Transcranial focused ultrasound (FUS) is increasingly being explored to modulate neuronal activity. To target neuromodulation, researchers often localize the FUS beam onto the brain region(s) of interest using spatially tracked tools overlaid on pre-acquired images. Here, we quantify the accuracy of optically tracked image-guided FUS with magnetic resonance imaging (MRI) thermometry, evaluate sources of error and demonstrate feasibility of these procedures to target the macaque somatosensory region. METHODS: We developed an optically tracked FUS system capable of projecting the transducer focus onto a pre-acquired MRI volume. To measure the target registration error (TRE), we aimed the transducer focus at a desired target in a phantom under image guidance, heated the target while imaging with MR thermometry and then calculated the TRE as the difference between the targeted and heated locations. Multiple targets were measured using either an unbiased or bias-corrected calibration. We then targeted the macaque S1 brain region, where displacement induced by the acoustic radiation force was measured using MR acoustic radiation force imaging (MR-ARFI). RESULTS: All calibration methods enabled registration with TRE on the order of 3 mm. Unbiased calibration resulted in an average TRE of 3.26 mm (min-max: 2.80-4.53 mm), which was not significantly changed by prospective bias correction (TRE of 3.05 mm; 2.06-3.81 mm, p = 0.55). Restricting motion between the transducer and target and increasing the distance between tracked markers reduced the TRE to 2.43 mm (min-max: 0.79-3.88 mm). MR-ARFI images showed qualitatively similar shape and extent as projected beam profiles in a living non-human primate. CONCLUSIONS: Our study describes methods for image guidance of FUS neuromodulation and quantifies errors associated with this method in a large animal. The workflow is efficient enough for in vivo use, and we demonstrate transcranial MR-ARFI in vivo in macaques for the first time.

Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter: A Multicenter, Randomized, Controlled Clinical Trial (PARAT).

BACKGROUND AND PURPOSE: Although flow diverters have been reported with favorable clinical and angiographic outcomes in various literatures, randomized trials determining their true effectiveness and safety are still in lack. The Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter (PARAT) trial was designed to evaluate the safety and efficacy of the Tubridge flow diverter in the treatment of large or giant aneurysms in comparison with Enterprise stent-assisted coiling. MATERIALS AND METHODS: This prospective, multicenter, randomized trial was conducted at 12 hospitals throughout China. Enrolled adults with unruptured large/giant intracranial aneurysms were randomly assigned (1:1) to receive either Enterprise stent-assisted coiling or Tubridge flow diverter implantation. The primary end point was complete occlusion at 6-month follow-up, while secondary end points included technical success, mortality, target vessel-related stroke, aneurysm bleeding, in-stent stenosis, parent artery occlusion, and the frequency of all adverse events. RESULTS: Among 185 enrolled subjects, 41 withdrew before procedure initiation. Overall, 82 subjects underwent Tubridge implantation, and 62 subjects were primarily treated with stent-assisted coiling. The results of 6-month follow-up imaging included complete occlusion rates of 75.34% versus 24.53% for the Tubridge and stent-assisted coiling groups, respectively, with a calculated common odds ratio of 9.4 (95% confidence interval, 4.14-21.38; P < .001). There was a higher, nonsignificant frequency of complications for Tubridge subjects. Multivariate analysis showed a decreased stroke rate at the primary investigational site, with a marginal P value (P = .051). CONCLUSIONS: This trial showed an obviously higher rate of large and giant aneurysm obliteration with the Tubridge FD over Enterprise stent-assisted coiling. However, this higher obliteration rate came at the cost of a nonsignificantly higher rate of complications. Investigational site comparisons suggested that a learning curve for flow-diverter implantation should be recognized and factored into trial designs.

Long-Term Outcome of Tubridge Flow Diverter(S) in Treating Large Vertebral Artery Dissecting Aneurysms-A Pilot Study.

BACKGROUND AND PURPOSE: The experience of flow diverters (FDs) in treating large vertebral artery-dissecting aneurysms (VADAs) is still limited. This study was conducted to present our long-term outcome of VADAs treated with a Tubridge flow diverter (TFD), a new device developed in China. MATERIALS AND METHODS: The clinical and angiographic data of six patients harboring large VADAs and treated with TFDs were prospectively collected and analyzed. RESULTS: A total of nine TFDs were successfully implanted in six patients. Angiographic follow-up images were available for all patients at a median of 26.0 (18.5, 37.5) months after treatment. Five of the six VADAs were completely occluded, and the last was improved (near complete occlusion). In-stent stenosis was detected in one case and was handled appropriately by angioplasty and stenting. All covered branches and parent arteries remained patent. There were no complications or new neurological deficits observed in any of the patients. At the latest clinical follow-up (36.5 (26.0, 44.5) months), all patients achieved 0 in the modified Rankin scale score. CONCLUSIONS: Our preliminary experience suggests that the Tubridge flow diverter might be an alternative treatment for large and recurrent dissecting aneurysms derived from the vertebral artery.

Drp-1, a potential therapeutic target for brain ischaemic stroke.

BACKGROUND AND PURPOSE: The resistance of CA3 neurons to ischaemia and the ischaemic tolerance conferred by ischaemic preconditioning (IPC) are two well-established endogenous neuroprotective mechanisms. Elucidating the molecules involved may help us find new therapeutic targets. Thus, we determined whether dynamin-related protein 1 (Drp-1) is involved in these processes. EXPERIMENTAL APPROACH: In vivo, we subjected rats to either 10 min severe global ischaemia using a four-vessel occlusion (4-VO) model or 2 min IPC before the onset of 4-VO. In vitro, we performed oxygen glucose deprivation (OGD) studies in rat hippocampal neurons. Drp-1 was silenced or inhibited by siRNA or pharmacological inhibitor Mdivi1. To assess whether mitochondrial Drp-1 alters neuronal vulnerability to ischaemic injury, various approaches were used including western blot, immunohistochemistry, immunofluorescence staining and electron microscopy. Hippocampal function was assessed using an open-field test. KEY RESULTS: Mitochondrial dynamin-related protein 1 (mtDrp-1) was selectively induced by ischaemia in hippocampal CA3 neurons. In hippocampal CA1 neurons, mtDrp-1 was not affected by ischaemia but significantly up-regulated by IPC. Suppression of Drp-1 increased the vulnerability of cells to OGD and global ischaemia. Inhibition of Drp-1 in vivo resulted in loss of acquisition and encoding of spatial information, and also prevented ischaemia-induced mitophagy in CA3. Thus mitochondrial-mediated injury was amplified and resistance to ischaemic injury lost. CONCLUSIONS AND IMPLICATIONS: Our findings that Drp-1 increases the resistance of neurons of hippocampal CA3 affected by global ischaemia and contributes to the tolerance conferred by IPC highlight Drp-1 as a potential therapeutic target for brain ischaemic stroke.

Tibia segment deformation in response to simulated muscle forces: a cadaveric study with a novel optical segment tracking (OST) approach.

OBJECTIVES: A novel optical segment tracking (OST) approach reliant upon motion capturing was previously proposed to assess human tibia segment deformation. The purposes of the present study were to validate the OST approach and assess the contribution of muscular forces to the bone deformation in a well-defined ex vivo human model. METHODS: A custom-made Lower Extremity Loading Device (LELD) was developed to simulate physiological muscle contractions in six human cadaveric lower extremities. Tibia segment deformation was measured by tracking the relative movement between two marker clusters which were affixed into the proximal and distal tibia, respectively. RESULTS: Compared to the physiological norms, the simulated muscle forces remained at a low level. When quadriceps muscle was loaded with forces from 198 N to 505 N, posterior bending (0.12°-0.25°) and lateral bending (0.06°-0.21°) of the tibia segment were found. Large tibia bending angles were found when simulating the co-contraction of upper leg muscles and plantar flexors, and of all leg muscles, respectively. The standard deviations of the deformation angles between the repetitions remained at a low level. CONCLUSIONS: We conclude that the OST approach has the potential to be applied in vivo and quantify muscle-induced bone deformations.

A novel flow-diverting device (Tubridge) for the treatment of 28 large or giant intracranial aneurysms: a single-center experience.

BACKGROUND AND PURPOSE: The Tubridge flow diverter is a novel device developed in China and aimed at reconstructing the parent artery and occluding the aneurysm. We conducted this study to evaluate its feasibility, safety, and efficacy for the treatment of large or giant internal carotid artery aneurysms, which are still challenging with conventional therapy. MATERIALS AND METHODS: The clinical and angiographic data of 28 patients with 28 large or giant internal carotid artery aneurysms treated with Tubridge flow diverters were prospectively collected and analyzed. RESULTS: Thirty-three Tubridge flow diverters were successfully implanted except for 1 poor midstent opening; the result was a technical success rate of 97.0% (32/33). Follow-up angiographies were available for 25 aneurysms; the mean follow-up was 9.9 months (5-24 months). Of the 25 aneurysms, 18 (72.0%) were completely occluded, 6 (24.0%) were improved, and 1 (4.0%) was unchanged. All of the visible covered branches and parent arteries were patent, with no stenosis or obliteration. During a follow-up of 6-30 months (mean, 19 months), symptoms were resolved in 13 patients, improved in 6 patients, and unchanged in 4 patients. Five patients experienced transient clinical deterioration due to a postoperative increased mass effect. Procedure-related morbidity and mortality were both zero. CONCLUSIONS: Our preliminary experience shows that the Tubridge flow diverter is a safe and effective tool for treating large and giant internal carotid artery aneurysms. However, multicenter randomized trials and studies involving a long-term follow-up are necessary.

In vivo measurements of human bone deformation using optical segment tracking: surgical approach and validation in a three-point bending test.

The purpose of the study was to validate optical segment tracking, a new method for in vivo human tibia deformation measurements and to assess bending in a three-point bending test. The approach relies upon optical motion capturing of reflecting marker clusters affixed to the bone via screws inserted three millimeters into the corticalis in local anesthesia. The method was tested in five healthy subjects. Screws were left in place for six to eight hours and a variety of exercises performed. A pain questionnaire was used to assess pain levels. PQCT-images were taken to locate screw holes in the bone. A three-point bending test was performed and repeatability evaluated. The new method shows good feasibility though this was previously considered impossible by many experts. Local anesthesia works for screw implantation and explantation. Results show linearity with an average of 0.25 degrees per 10 kg of weight applied with good repeatability (average variation coefficient 8%). Optical segment tracking is feasible for human in vivo bone deformation measurements. There is a variety of possible clinical and experimental applications including stability testing of osteosyntheses and joints, monitoring of bone healing, evaluation of exercises in physiotherapy, and assessment of bone deformation patterns in bone disease.

Association between fibroblast growth factor receptor 4 Gly388Arg polymorphism and ischaemic stroke.

OBJECTIVE: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in the vascular system. The FGFR4 rs351855 (Gly388Arg) poly morphism has been shown to be a risk factor for many diseases. This case-control study investigated the association between the FGFR4 Gly388Arg polymorphism and susceptibility to ischaemic stroke in the Chinese population. METHODS: The FGFR4 Gly388Arg polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in patients with ischaemic stroke and healthy controls. RESULTS: Frequencies of genotypes GA and AA, and prevalence of the A allele, were significantly lower in ischaemic stroke patients (n = 952) than in controls (n = 986). Genotype AA and allele A were significantly more frequent in stroke patients with, than in those without, diabetes. CONCLUSION: These results suggested that the GA genotype, AA genotype and A allele of FGFR4 Gly388Arg polymorphism are all associated with decreased risk of ischaemic stroke in the Chinese population.

Y-configuration stent placement (crossing and kissing) for endovascular treatment of wide-neck cerebral aneurysms located at 4 different bifurcation sites.

BACKGROUND AND PURPOSE: The Y-stent technique, including crossing-Y and kissing-Y, is a promising therapeutic option for some complex bifurcation aneurysms. Here, its efficacy and safety are evaluated on the basis of 11 bifurcation aneurysms. MATERIALS AND METHODS: A retrospective review was conducted for all patients who underwent endovascular treatment of aneurysms in our department between January 2009 and June 2011 to identify and analyze cases with bifurcation aneurysms reconstructed by using Y-stents. RESULTS: Eleven patients (4 ruptured and 7 unruptured aneurysms) were identified (4 men, 7 women) with a mean age of 60.4 years. Nine aneurysms (2 AcomAs, 3 MCA-Bifs, 1 PcomA, 3 BA apexes) were treated by using the crossing-Y technique, and 2 (both BA apexes) were treated with the kissing-Y technique, achieving complete occlusion in 6 aneurysms, residual neck in 4, and partial occlusion in 1. Perioperatively, a single thromboembolic event occurred in 1 case without neurologic deficit, which required a salvaging second stent implantation. Means of 9.9 months of angiographic and 13.7 months of clinical follow-up were available. As a result, 9 (81.8) aneurysms were completely occluded, 1 with a residual neck remained stable, and 1 residual aneurysm sac was recanalized, which was retreated and achieved a complete occlusion. All patients were independent with an mRS score of 0-1 at discharge and follow-up. CONCLUSIONS: In selected patients, the reconstruction of bifurcation aneurysms by using the Y-stent can be successfully achieved with satisfactory midterm results.

What do we currently know from in vivo bone strain measurements in humans?

Bone strains are the most important factors for osteogenic adaptive responses. During the past decades, scientists have been trying to describe the relationship between bone strain and bone osteogenic responses quantitatively. However, only a few studies have examined bone strains under physiological condition in humans, owing to technical difficulty and ethical restrictions. The present paper reviews previous work on in vivo bone strain measurements in humans, and the various methodologies adopted in these measurements are discussed. Several proposals are made for future work to improve our understanding of the human musculoskeletal system. Literature suggests that strains and strain patterns vary systematically in response to different locomotive activities, foot wear, and even different venues. The principal compressive, tension and engineering shear strain, compressive strain rate and shear strain rate in the tibia during running seem to be higher than those during walking. The high impact exercises, such as zig-zag hopping and basketball rebounding induced greater principal strains and strain rates in the tibia than normal activities. Also, evidence suggests an increase of tibia strain and strain rate after muscle fatigue, which strongly supports the opinion that muscle contractions play a role on the alteration of bone strain patterns.

Effect of cell membrane of Agrobacterium radiobacter on enhancing D-amino acids production from racemic hydantoins.

An interesting phenomenon was observed that the existence of the intact cell membrane can enhance the D-amino acids production from D,L-5-substituted hydantoins by reacting with the whole cells of Agrobacterium radiobacter. Two intracellular enzymes were involved in the reaction process. The first enzyme D-hydantoinase converted hydantoins to carbamoyl derivatives which were further converted to D-amino acids by D-amidohydrolase. The amount of D-amino acids produced from hydantoins by the intact cells were 1.8-2.4 fold higher than the toluene treated cells. In addition, by using the intact cells the amount of D-amino acids produced from hydantoins was about 10 fold higher than that produced directly from carbamoyl derivatives. The relatively lower permeability of cell membrane to the reaction intermediate carbamoyl derivatives was confirmed by a simple mathematical model to be the main factor for the better performance of the intact cells for D-amino acid production. Besides, the low intracellular enzymes activities also contributed to the effect of intact cell membrane on enhancing the D-amino acid production.

Serotonergic regulation of crustacean hyperglycemic hormone secretion in the crayfish, Procambarus clarkii.

These studies investigate if crustacean hyperglycemic hormone (CHH) is involved in 5-hydroxytryptamine (5-HT)-induced hyperglycemia. Eyestalk ganglia with intact X-organ-sinus gland complex were dissected from the crayfish Procambarus clarkii and incubated under various experimental conditions. Incubation media were then analyzed for the presence of released hyperglycemic factor using an in vivo bioassay. The results show that 5-HT enhanced release of hyperglycemic factor in a dose-dependent manner. This stimulatory effect of 5-HT was significantly decreased by adding ketanserin or methysergide (both 5-HT receptor antagonists) into incubation of eyestalk ganglia. Further, activity of the 5-HT-released hyperglycemic factor could be eliminated by adsorption of incubation media with anti-CHH serum but not by preimmune or anti-5-HT serum. These results confirm the hypothesis that 5-HT enhances release of CHH, which in turn elicits hyperglycemic responses. It is probable that 5-HT activates an excitation-secretion coupling mechanism by interacting with receptors located on the X-organ neurosecretory cells.

Filamentous actin disruption and diminished inositol phosphate response in gingival fibroblasts caused by Treponema denticola.

Previous reports have shown that Treponema denticola causes rearrangement of filamentous actin (F-actin) in human gingival fibroblasts (HGF). The purpose of this investigation was to determine the effect of T. denticola on the generation of inositol phosphates (IPs) in relation to a time course for F-actin disruption in HGF. Cultured HGF were exposed to washed cells of T. denticola ATCC 35405 for 140 min. Changes in the fluorescence intensity of rhodamine-phalloidin-labeled F-actin in serial optical sections of single HGF were quantified by confocal microscopy image analysis. The percentage of cells with stress fiber disruption was also determined by fluorescence microscopy. Challenge with T. denticola caused a significant reduction in F-actin within the first hour, especially at the expense of F-actin in the ventral third of the cells, and a significant increase in the percentage of HGF with altered stress fiber patterns. Significant concentration-dependent disruption of stress fibers was also caused by HGF exposure to a Triton X-100 extract of T. denticola outer membrane (OM). IPs were measured by a radiotracer assay based on the incorporation of myo-[3H]inositol into IPs in HGF incubated with LiCl to inhibit endogenous phosphatases. HGF challenge with several strains of T. denticola and the OM extract of T. denticola ATCC 35405 resulted in a diminished accumulation of radiolabeled IPs relative to both 15 and 1% fetal bovine serum, which served as strongly positive and background control agonists, respectively. The significantly diminished IP response to T. denticola ATCC 35405 occurred within 60 min, concomitant with significant reduction of total F-actin and disruption of stress fibers. Pretreatment with the proteinase inhibitor phenylmethylsulfonyl fluoride, which had previously been found to block T. denticola's degradation of endogenous fibronectin and detachment of HGF from the extracellular matrix, had little effect on F-actin stress fiber disruption and the IP response. Therefore, in addition to its major surface chymotrypsin-like properties, T. denticola expresses cytopathogenic activities that diminish the generation of IPs during the time course associated with significant cytoskeletal disruption in fibroblasts.

In vitro sensitivity of Plasmodium falciparum to eight antimalarials in China-Myanmar and China-Lao PDR border areas.

In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China-Myanmar border areas were tested. The resistant rates of P. falciparum to chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and arteether. Resistant rates from other areas were 0-11%. P. falciparum from China-Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68-88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on the China-Lao PDR border showed that the average defervescent time of falciparum malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during 1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2% to 37.5%. The results monitored in vitro showed that all cases assessed in 1988 for response to pyronaridine were sensitive, but 36.4% of cases had emerging resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results suggested that P. falciparum in these areas has expressed resistance to chloroquine and amodiaquine. However, the parasites are still sensitive to artemisinin, pyronaridine, mefloquine, quinine, but with a declining sensitivities.