Efficacy and Safety of Parenteral Injection of an Extended Release κ-receptor Opioid Sebacoyl Dinalbuphine Ester for Acute and Chronic Pain After Laparoscopic Bariatric Surgery: a Randomized, Placebo-Controlled, Double-Blind Trial.

PURPOSE: µ-receptor opioids are associated with unwanted gastrointestinal side effects and respiratory depression. A long-acting non-µ-receptor parenteral opioid is not currently available for management of acute and chronic postsurgical pain (CPSP). This double-blind clinical trial tested an extended-release κ-receptor agonist, sebacoyl dinalbuphine ester (SDE, Naldebain®) for management of surgical pain after laparoscopic bariatric surgery. MATERIALS AND METHODS: Patients were randomly assigned to receive a single intramuscular injection of SDE (150 mg, n = 30) or vehicle solution (n = 30) at > 12 h before surgery. All patients received standard perioperative multimodal analgesia (MMA). The primary endpoint was the pain intensity in the beginning 7 days after operation. The secondary endpoints were adverse reactions up to 7 days and incidence of CPSP at 3 months after surgery. RESULTS: Compared with placebos, the area under curves of visual analog scale (VAS) for 0-48 h after operation were significantly reduced in SDE group (143.3 ± 65.4 and 105.9 ± 36.3, P = 0.025). There were significantly fewer patients in the SDE group who had moderate-to-severe pain (VAS ≥ 4) (16.7% vs 50%; P = 0.012) at postoperative 48 h. Pain intensities were similar between the two groups at 72 h and 7 days postoperatively. The incidence of CPSP at 3 months was not different. SDE did not increase drug-related systemic adverse events. CONCLUSION: In addition to the standard perioperative MMA, a single-dose injection of long-acting κ-receptor agonist SDE provides significantly better pain management for 48 h following laparoscopic bariatric surgery. A long-acting κ-receptor agonist opioid could improve in-hospital pain management and potentiate early discharge after operation without increasing drug-related systemic complications.

Spatiotemporal evolution of pyroptosis and canonical inflammasome pathway in hSOD1G93A ALS mouse model.

BACKGROUND: Evidences indicate that inflammasome compounds participate in amyotrophic lateral sclerosis (ALS), a fatal progressive motoneuron degenerative disease. Researchers have observed the expressions of nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) related inflammasome components in specific regions of the central nervous system in different ALS models, but the cellular spatiotemporal evolution of this canonical inflammasome pathway and pyroptosis during ALS progression are unclear. METHODS: The spinal cords of hSOD1G93A mice (ALS mice) and age-matched littermates (CON mice) were dissected at pre-symptomatic stage (60 d), early- symptomatic stage (95 d), symptomatic stage (108 d) and late-symptomatic stage (122 d) of the disease. By using Nissl staining, double immunofluorescence labelling, qRT-PCR or western blot, we detected morphology change and the expression, cellular location of GSDMD, NLRP3, caspase-1 and IL-1ß in the ventral horn of lumbar spinal cords over the course of disease. RESULTS: Neural morphology changes and GSDMD+/NeuN+ double positive cells were observed in ventral horn from ALS mice even at 60 d of age, even though there were no changes of GSDMD mRNA and protein expressions at this stage compared with CON mice. With disease progression, compared with age-matched CON mice, increased expressions of GSDMD, NLRP3, activated caspase-1 and IL-1ß were detected. Double immunofluorescence labeling revealed that NLRP3, caspase-1, IL-1ß positive signals mainly localized in ventral horn neurons at pre- and early-symptomatic stages. From symptomatic stage to late-symptomatic stage, robust positive signals were co-expressed in reactive astrocytes and microglia. CONCLUSIONS: Early activation of the canonical NLRP3 inflammasome induced pyroptosis in ventral horn neurons, which may participate in motor neuron degeneration and initiate neuroinflammatory processes during ALS progression.

Aquatic risk assessment of a novel strobilurin fungicide: A microcosm study compared with the species sensitivity distribution approach.

The ecotoxicological effects of pyraoxystrobin, a novel strobilurin fungicide, were studied using outdoor freshwater microcosms and the species sensitivity distribution approach. The microcosms were treated with pyraoxystrobin at concentrations of 0, 1.0, 3.0, 10, 30 and 100µg/L. Species sensitivity distribution (SSD) curves were constructed by means of acute toxicity data using the BurrliOZ model for fourteen representatives of sensitive invertebrates, algae and fish and eleven taxa of invertebrates and algae, respectively. The responses of zooplankton, phytoplankton and physical and chemical endpoints in microcosms were studied. Zooplankton, especially Sinodiaptomus sarsi was the most sensitive to pyraoxystrobin exposure in the microcosms. Short-term toxic effects (<8 weeks) on zooplankton occurred in 1µg/L treatment group. The duration of toxic effects on S. sarsi could not be evaluated within the initial 56 days. Significant long-term toxic effects were observed at 10, 30 and 100µg/L (>281 days) for S. sarsi and the zooplankton community. Based on the results obtained from the organisms in the microcosm system, 1µg/L was recommended as the NOEAEC (no observed ecologically adverse effect concentration). Also, 0.33µg/L was derived as the Regulatory Acceptable Concentration based on the ecological recovery option (ERO-RAC) of pyraoxystrobin. For all fourteen tested species, the median HC5 (hazardous concentration affecting 5% of species) was 0.86µg/L, and the lower limit HC5 (LL-HC5) was 0.39µg/L. For the eleven taxa of invertebrates and algae tested, the median HC5 was 1.1µg/L, and the LL-HC5 was 0.26µg/L. The present study positively contributes to the suggestion of adequately using acute L(E)C50-based HC5/ LL-HC5 for deriving protective concentrations for strobilurin fungicides, and it should be valuable for full comprehension of the potential toxicity of pyraoxystrobin in aquatic ecosystems.

Correlation between genetic polymorphism of matrix metalloproteinase-9 in patients with coronary artery disease and cardiac remodeling.

OBJECTIVE: To explore the correlation between genetic polymorphism of matrix metalloproteinase-9 (MMP-9) in patients with coronary artery disease (CAD) and cardiac remodeling. METHODS: A total of 272 subjects who received coronary angiography in our hospital from July 2008 to September 2013 were selected, including 172 CAD patients (CAD group) and another 100 ones (control group). Both groups were subjected to MMP-9 and ultrasonic detections to determine vascular remodeling and atherosclerotic plaques. C1562G polymorphism of MMP-9 gene was detected, and correlation with vascular remodeling and atherosclerotic plaque was analyzed. RESULTS: Serum MMP-9 level of CAD group (330.87±50.39 ng/ml) was significantly higher than that of control group (134.87±34.02 ng/ml) (P<0.05). Compared with control group, CAD group had significantly higher intima-media thickness, and significantly lower systolic peak velocity, mean systolic velocity and end-diastolic velocity (P<0.05). Total area of stenotic blood vessels was 67.34±22.98 mm(2), while that of control blood vessels was 64.00±20.83 mm(2). G/G, G/C and C/C genotype frequencies of MMP-9 differed significantly in the two groups (P<0.05). G and C allele frequencies of CAD group (70.9% and 29.1%) were significantly different from those of control group (50.0% and 50.0%) (P<0.05). G/G, G/C and C/C genotypes were manifested as lipid-rich, fibrous and calcified or ulcerated plaques respectively. Total area of stenotic blood vessels of G/G genotype significantly exceeded those of G/C and C/C genotypes (P<0.05), whereas the latter two had no significant differences. CONCLUSION: CAD promoted 1562C-G transformation of MMP-9 gene into genetic polymorphism, thus facilitating arterial remodeling and increasing unstable atherosclerotic plaques.

Endovascular repair of a tuberculous aneurysm of descending thoracic aorta.

Tuberculous aortic aneurysm (TBAA) is an extremely rare clinical event with life-threatening implication. Management for this condition is challenging and its therapeutic option has not been yet established. A few recent reports described endovascular repair rather than open surgery as the method for treatment. Although this remains controversial, endovascular exclusion has been gaining acceptance for some surgeons. We present a case of TBAA who was treated by endovascular stent grafting for a descending thoracic aortic aneurysm with simultaneous anti-tuberculous medication. The outcome was favorable.

[Evaluation of efficacy of the anticoagulation and thrombolysis for deep venous thrombosis via local vein approach and peripheral vein approach].

OBJECTIVE: To investigate the efficacy of anticoagulation and thrombolysis for deep venous thrombosis via local vein approach and peripheral vein approach to guide clinical treatment. METHODS: There were 225 patients with deep venous thrombosis admitted from January 2001 to May 2008. The cases were divided into two groups by therapy procedures. The patients in group A were treated by deep femoral vein catheter-directed anticoagulation and thrombolysis, including a total number of 71 patients, with right lower extremity in 20 patients, left lower extremity in 47 patients and bilateral lower extremities in 4 patients. One hundred and fifty-four patients were included in group B with anticoagulation and thrombolysis through peripheral vein, among them right lower extremity in 27 patients, left lower extremity in 121 patients and bilateral lower extremities in 6 patients. The efficacy was evaluated and compared by observing clinical symptoms and measuring of changes in limb circumference. RESULTS: Symptoms were alleviated in all patients in 3 d after the treatment, but the efficacy of group A was better than group B (94.4% vs.69.5%, P < 0.01). The efficacy of group A was also better than group B in 7 days after treatment, but with no significant difference (85.9% vs. 75.3%, P > 0.05). A mean follow-up period was (43 ± 18) months. There was no significant difference in incidence of complication and recurrence between two groups. CONCLUSIONS: The earlier efficacy of anticoagulation and thrombolysis via femoral vein approach is better than via peripheral vein approach in earlier period of deep venous thrombosis. While peripheral intravenous therapy has also good results after long-term treatment.

Inflammatory abdominal aortic aneurysm: clinical features and long term outcome in comparison with atherosclerotic abdominal aortic aneurysm.

BACKGROUND: Inflammatory abdominal aortic aneurysms (IAAAs) are rare but distinct clinical entities of atherosclerotic abdominal aortic aneurysms (aAAAs). In this study we report a 20-year single institution experience for IAAA and analyze their clinical features and long term outcome in comparison with aAAA. METHODS: Between 1988 and 2008, 412 cases of abdominal aortic aneurysms (AAAs) underwent elective surgical operations, 11 (2.7%) of whom were diagnosed as IAAAs and 389 (94.4%) were diagnosed as aAAAs. The former group was matched in a case control fashion to a group of 33 patients with aAAAs having similar characteristics of age, gender, and preoperative risk factors. All available clinical, pathologic, and postoperative variables were retrospectively reviewed, and the two groups were compared. RESULTS: The two groups did not differ significantly in clinical characteristics and preoperative risk factors, although patients with IAAAs were significantly more symptomatic (100% vs. 42.4%, P = 0.001) and had larger aneurysms on admission ((7.4 +/- 0.7) cm vs. (6.3 +/- 0.9) cm, P = 0.006). In IAAAs, the preoperative erythrocyte sedimentation rate was found to be significantly elevated compared to aAAA group ((44.5 +/- 9.1) mm/h vs. (11.4 +/- 5.4) mm/h, P < 0.05). Surgical morbidity and mortality rates did not differ between the two groups. The operation time for patients with IAAAs was significantly longer than that for patients with aAAAs ((308 +/- 36) minutes vs. (224 +/- 46) minutes, P < 0.05), but the cross-clamp time was similar in both groups ((41.5 +/- 6.2) minutes vs. (41.8 +/- 6.2) minutes, P = 0.92). A five-year survival rate analysis showed no significant difference between the two groups (P = 0.711). CONCLUSIONS: Despite having more symptoms, larger size and longer operation time, patients with IAAA can now be treated with approaches that cause low morbidity and mortality, similar to patients with aAAA. Long term outcome of IAAA patients is of no difference from aAAA patients.

Deficient CD4+CD25+ T regulatory cell function in patients with abdominal aortic aneurysms.

OBJECTIVE: Increasing evidence shows that autoimmune response contributes importantly to pathogenesis of abdominal aortic aneurysm (AAA). This work was aimed to assess the possibly altered function of peripheral CD4(+)CD25(+) T regulatory cells (Tregs) that might breakdown immunologic self-tolerance in AAA patients. METHODS AND RESULTS: Peripheral blood from 22 AAA patients, 11 patients with abdominal aortic atherosclerotic occlusive disease (AOD), and 32 healthy controls (HCs) was analyzed to determine the percentage of CD4(+)CD25(+) Tregs in the total CD4(+) T-cell population and FOXP3 expression by means of flow cytometry. The frequencies of the CD4(+)CD25(+) Treg population were not significantly different between groups (AAA, 5.69+/-0.99%; AOD, 5.52+/-1.13%; HC, 5.88+/-1.55%; P>0.05). However, the frequency of CD4(+)CD25(+)FOXP3(+) T cells in AAA patients (2.45+/-0.57%) was significantly lower than that in AOD group (3.41+/-0.72%; P<0.01) or in HCs (3.69+/-0.82%; P<0.01). A comparison of FOXP3 mRNA and protein expression revealed significantly lower levels in CD4(+)CD25(+) Tregs from AAA group than either of other 2 groups (P<0.01). Suppressive function assay showed that freshly isolated CD4(+)CD25(+) Tregs from patients with AAA exhibited significantly less suppressive activity than those from AOD patients or HCs (P<0.01). Mixing cultures with CD4(+)CD25(+) T cells and CD4(+)CD25(-) T cells from AAA patients and HCs demonstrated that the primary regulatory defect is due to a dysfunction of CD4(+)CD25(+) Tregs, and not a resistance of CD4(+)CD25(-) responder T cells to suppression in AAA patients. CONCLUSIONS: Our data demonstrate a reduced level of FOXP3 expression in peripheral CD4(+)CD25(+) Tregs and decreased frequency of CD4(+)CD25(+)FOXP3(+) T cells in a cohort of AAA patients enrolled in the study, which leads to a functional deficiency of CD4(+)CD25(+) Tregs as a whole. This indicates an impaired immunoregulation by Tregs that may contribute to AAA pathogenesis.

[The diagnosis and therapy of acute upper limbs deep venous thrombosis].

OBJECTIVE: To conclude the experience of diagnosis and therapy, the effect analysis and the prognosis factors of acute upper limbs deep venous thrombosis (ULDVT). METHODS: We retrospectively analyzed the etiological factor, clinical manifestation, diagnosis, therapy and prognosis of 28 patients treated for acute ULDVT admitted in our hospital between 1988 and 2009. The patients were divided into two groups according to the time of admission and management in hospital. Group I, from 1988 to 1998, and group II, from 1999 to 2009. RESULTS: There were 28 patients diagnosed as acute ULDVT, which was 8.1% of lower limbs deep venous thrombosis in synchronization. There were 14 men and 14 women, and the mean age was 46.1 years. 17 patients developed in left upper limbs, and 11 patients developed in right upper limbs. There were 9 patients in group I and 19 in group II. A significant difference was observed between two groups in their risk factors, primary and secondary cause. 8 patients (28.6%) were relevant to venepuncture catheterization, and 13 patients (46.4%) have tumors. There is clear difference between the two groups in the way of primary disease and risk Factors, which means that the probability of ULDVT caused by malignant tumors or other factors in group II is apparently higher than group I, and the prognosis of group II is worse compared with group I. All the patients in the group were made a definite diagnosis by ultrasound, after that our policy were thrombolysis and anticoagulation followed by Warfarin oral administration for 6 months. All the conditions of the patients were well improved, and the symptoms were relieved obviously and discharged. The mean follow-up duration was 2.2 years. 2 recurred, 1 was pulmonary infarction, and 6 was died. CONCLUSION: The incidence of ULDVT is much lower than LLDVT. The motivations are blood hypercoagulable state, such as tumor, vein catheterization etc. The final diagnosis is mostly based on clinical manifestation combined with ultrasound. Thrombolysis, anticoagulation in time have an obvious therapy effect. After that the anticoagulation therapy through oral administration can prevent recurrence.