Effect of selective β-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine,and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquidgastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), andantipyrine (At). The present study aimed to determine whether β-adrenoceptors areinvolved in delayed GE induced by phenylpyrazole derivatives and the role of theprevertebral sympathetic nervous system in this condition. Male Wistar rats weighing220-280 g were used in the study. In the first experiment rats were intravenouslypretreated with vehicle (V), atenolol 30 mg/kg (ATE, β₁-adrenergicantagonist), or butoxamine 25 mg/kg (BUT, β₂-adrenergic antagonist). Inthe second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA,β₃-adrenergic antagonist). In the third experiment, rats were subjectedto surgical resection of the celiac-superior mesenteric ganglion complex or to shamsurgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA,or At, 15 min after pretreatment with the antagonists or V and nine days aftersurgery. GE was determined 10 min later by measuring the percentage of gastricretention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR(means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dpvs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At(BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE,and significantly reduced (P<0.05) the effect of AA (BUT+AA vsV+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did notmodify the effects of treatments. These results suggest thatβ₂-adrenoceptor activation occurred in delayed liquid gastric emptyinginduced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, andantipyrine. Additionally, the released neurotransmitter did not originate in theceliac-superior mesenteric ganglion complex.     

Effect of cysteine on gastric mucosal lesion induced by restraint water-immersion in rats

目的：研究半胱氨酸对大鼠胃溃疡的影响及其作用机制。方法：利用大鼠浸水应激性胃溃疡模型，观察腹注盐酸半胱氨酸对胃溃疡指数、胃粘膜谷胱甘肽（ＧＳＨ）含量、胃酸分泌和胃粘液分泌的影响。结果：半胱氨酸能抑制大鼠胃溃疡的形成；浸水应激可使大鼠胃粘膜ＧＳＨ含量明显降低，半胱氨酸对ＧＳＨ含量的降低无影响；事先给予Ｎ－乙酰马来酰氨（Ｎ－ｅｔｈｙｌｍａｌｅｉｍｉｄｅ，ＮＥＭ）或消炎痛对半胱氨酸的抗溃疡作用无影响；半胱氨酸能抑制浸水应激大鼠胃酸的分泌，但对胃粘液的分泌无影响。结论：半胱氨酸的抗溃疡作用与其抑制胃酸分泌有关，而与胃粘液的分泌、胃粘膜ＧＳＨ和前列腺素的作用无关。     

Daily variations of epinephrine, norepinephrine, and β-adrenoceptors in the blood and lymphoid organs of intact rats

Daily variations of catecholamine concentrations in the blood and lymphoid organs in Wistar rats were revealed. Daily fluctuations of epinephrine and norepinephrine levels in the spleen and blood were synchronous. Circadian variations of epinephrine in the thymus, lymph nodes, and plasma were synphasic. A relationship between neurotransmitter concentrations and expression of β-adrenoceptors on thymic and splenic lymphocytes was noted. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 9, pp. 344–346, September, 1999     

Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-β1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-β1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-β1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT‐PCR technique was more sensitive to expression changes than the semiquantitative method.     

Skill,Judgement and Conduct for the First Generation of Neurosurgeons, 1900–1930

Historical contingency complicates a reading of skill as a self-explanatory and alwayspositive attribute. By focusing on the attempts of the first generation of neurosurgeonsto build a community and fashion a collective neurosurgical self, this article highlightsthe extent to which the relationship between surgical skill and professional judgement isreflected in broader concerns that shape the landscape of medicine at a given time. Someearly twentieth-century surgeons expressed concern about the spectacularisation of surgeryand the skilful but problematic work of ‘brilliant operators’. The neurosurgeons’ policiesof inclusion and exclusion show that in the process of fashioning a neurosurgical persona,this first generation sanctioned specific norms of conduct underwritten by similar moralimperatives, such as self-control. These norms governed the doctors’ work both in theoperating room and on the public stage (in their engagement with the press). The meetingsof the first neurosurgical society staged a critical encounter between the hostneurosurgeon and the members who watched him perform surgery. These technical performancesin the operating theatre, followed by discussions, were designed to encourage particularnorms, to negotiate surgical knowledge, and to demonstrate the skills and character of theneurosurgeon. The performances acted as a technology of the self that aligned the operatorto a community and helped that community refine its norms of surgical conduct. The awkwardsurgeon with inferior technical ability was preferable to the brilliant but vain operatorwho lacked the capacity to judge when he should not deploy his spectacular skills.     

Evidence for the involvement of adenomatous polyposis coli (APC) protein in maintaining cellular distributions of α3β4 nicotinic receptors

Recent developments in depression studies have heightened the need for investigating adolescent major depressive disorder (MDD). Many previous neuroimaging studies used task designs and found consistent results in the dysfunction of brain regions in depressed adolescent patients. In this study, we aimed to evaluate the topological properties of brain functional networks of adolescents with MDD from an integrated view. Using resting state functional magnetic resonance imaging (fMRI), graph theory was applied to construct the resting networks in 16 first-episode and unmedicated adolescents with MDD and 16 healthy controls (HC). Our results showed that the topological properties of depressed adolescents’ networks were significantly disrupted compared with HC. Dysregulation of brain regions were found in the anterior cingulate cortex, dorsolateral, medial and inferior prefrontal cortex, insula, amygdala, and the temporal cortices. Furthermore, the connectivity degree of amygdala related functional connection was positively correlated with the duration of depression. Detection and estimation of these functional impairments may advance our current understanding of the pathophysiological mechanism of adolescent MDD.     

Evidence for the involvement of adenomatous polyposis coli (APC) protein in maintaining cellular distributions of α3β4 nicotinic receptors

Evidence exists supporting the involvement of adenomatous polyposis coli (APC) protein in the assembly of neuronal nicotinic acetylcholine receptors (nAChRs) in the postsynaptic complex. In the following studies, the effects of APC protein on cellular distribution of recombinant α3β4 nAChRs was investigated. RT-PCR and Western blotting techniques established the expression of APC protein both in bovine adrenal chromaffin cells, which express native α3β4* nAChRs, and in a HEK293 cell line expressing recombinant bovine adrenal α3β4 nAChRs (BMα3β4 cells). Transfection of BMα3β4 cells with siRNA to APC, reduced APC protein levels to 52.4% and 61.9% of control values at 24 and 48 h after transfection. To investigate the effects of APC on the cellular distribution of α3β4 nAChRs, [³H]epibatidine binding approaches, coupled with APC siRNA treatment, were used. Twenty-four and 48 h after APC siRNA transfection, intracellular nAChRs were significantly reduced to 71% and 68% of control, respectively, while the total population of nAChRs were not significantly changed. Given that total cellular nAChRs represent the sum of surface and intracellular nAChRs, these studies support a re-distribution of nAChRs to the plasma membrane with APC siRNA treatment. Treatment of the cells with the protein synthesis inhibitor, puromycin, also caused a significant reduction (55%) in APC protein levels, and produced a similar re-distribution of cellular nAChRs. These studies support the involvement of APC protein in the maintenance of normal cellular distribution of α3β4 nAChRs.     

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α₂-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α₂-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α₂-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α₂-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α₂-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α₂-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.     

Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression

Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growthfactors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle.In the present study, we tested the hypothesis that ischemic postconditioning iseffective for salvaging ischemic skeletal muscle resulting from limbischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α.Wistar rats were randomly divided into three groups (n=36 each): sham-operated (groupS), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (groupIPO). Each group was divided into subgroups (n=6) according to reperfusion time:immediate (0 h, T₀), 1 h (T₁), 3 h (T₃), 6 h(T₆), 12 h (T₁₂), and 24 h (T₂₄). In the IPOgroup, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion werecarried out before reperfusion. At all reperfusion times(T₀-T₂₄), serum creatine kinase (CK) and lactatedehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumornecrosis factor-α (TNF-α) concentrations, were measured in rats after they werekilled. Histological and immunohistochemical methods were used to assess the skeletalmuscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR andIPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were allsignificantly increased compared to group S, and HIF-1α expression was up-regulated(P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α andIL-6 concentrations were significantly decreased, IL-10 concentration was increased,HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathologicalchanges were reduced compared to group IR. The present study suggests that ischemicpostconditioning can reduce skeletal muscle damage caused by limbischemia-reperfusion and that its mechanisms may be related to the involvement ofHlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.     

Possible involvement of NO/NOS signaling in hippocampal amyloid-β production induced by transient focal cerebral ischemia in aged rats

In the present study, to define the roles of nitric oxide (NO) signaling in amyloid-β (Aβ) production after transient cerebral ischemia, extracellular levels of NO and Aβ were monitored by intracerebral microdialysis in the hippocampus of aged rats exposed to transient middle cerebral artery occlusion and reperfusion (MCAO/R). The results indicated that 1-h MCAO significantly upregulated hippocampal NO and Aβ levels. In addition, the NO elevation preceded the Aβ changes. The Western blotting suggested that acute hypoperfusion could increase the expression of β-secretase 1 (BACE1) but not BACE2. The enhanced NO concentration in acute stage of MCAO/R was coincident with increased eNOS expression, while in subacute stage was coincident with increased iNOS and nNOS. Our results also indicated that pretreatment of L-NAME, one non-selective NOS inhibitor could decrease the BACE1 expression, reverse both NO and Aβ changes and rescue the delayed neuronal death. These preliminary findings indicated that activation of NOS/NO signaling system could trigger Aβ production through BACE1 pathway during acute ischemic episode. The present data may be important in understanding, at least in part, the pathological role of NO/NOS system involved in hippocampal Aβ production and neuronal damage induced by transient cerebral ischemia.     

Evidence for the involvement of K+ channels and K+-Cl– cotransport in the regulatory volume decrease of newborn rat cardiomyocytes

In order to delineate ion transport mechanisms involved in volume homeostasis of freshly isolated newborn rat ventricular myocytes, we investigated the effects of ion substitutions and pharmacological maneuvers upon (1) isotonic volume, (2) hypotonically induced initial swelling, and (3) the subsequent regulatory volume decrease (RVD), as determined by electronic cell sizing. Cardiomyocytes exposed to hypotonic medium (176 mosmol/l) swelled by 51+/-1% of isotonic volume, and they underwent a partial regulatory volume decrease (RVD), reaching a maximum regulation after 30 min (51+/-1% of initial swelling), with a half-time (t1/2) of 6+/-1 min (n=60). RVD was associated with significant cardiomyocyte K+ loss (12+/-4% at 5 min and 15+/-2% of isotonic control after 30 min: n=6, P<0.001), 71% of which was Cl- dependent (P<0.05). Within the 30-min experimental time frame, ouabain, a Na+/K+ pump inhibitor, had no significant effect on RVD (despite an inhibitory trend), cell swelling or on isotonic volume (n=6). Bumetanide (50 microM), a Na+-K+-Cl- co-transport blocker, induced a significant reduction of isotonic cell volume (3+/-2%, n=6. P<0.05), potentiated initial swelling by 16+/-1% (n=8, P<0.02), and it partially inhibited RVD (24+/-11% at 30 min, n=6), whereas Na+ omission had no significant effect on isotonic cell volume, cell swelling or RVD. The effects of bumetanide on initial swelling and RVD were prevented by gadolinium ion (10 microM), a stretch-activated cation channel blocker (n=5). Quinidine (500 microM), a non-selective Ca(2+)-activated potassium channel blocker with no side-effects on K(+)-Cl(-) cotransport, did not modify initial cell swelling, but inhibited RVD (50+/-3% at 5 min, n=9, P<0.01; 22+/-3% at 30 min), an effect which was cancelled by external Ca2+ chelation with EGTA (n=5), and reproduced by tetraethylammonium (TEA, 20 mM), another K+ channel blocker. 4,4'-Diisothiocyanatostilbene 2,2'-disulfonic acid (DIDS, 100 microM), a non-selective swelling-activated Cl- channel blocker with marginal side-effects on K(+)-Cl(-)cotransport, did not modify initial swelling, but inhibited RVD to the same extent as quinidine (42+/-3% at 5 min, and 23+/-3% at 30 min, n=15, P<0.05), whereas hypotonic Cl(-)-free solution had no effect on isotonic volume, but potentiated initial swelling by 16+/-2% (P<0.05) and fully inhibited RVD (n=5, P<0.001). R(+)-[(2-n-Butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inde n-5yl)-oxy] acetic acid) (DIOA, 80 microM), a K(+)-Cl- cotransport blocker (with inhibitory potency toward Ca(2+)-activated K+ channels), inhibited 87+/-5% of the RVD process at 5 min (P<0.001) and 56+/-16% at 30 min (P<0.001), whereas it had a small effect on isotonic volume (+4%, P<0.01) and initial cell swelling (+2%, N.S.; n=9). In contrast to quinidine, DIOA was able to inhibit Ca(2+)-omission-resistant RVD (full inhibition at 5 min, and 56+/-9% at 30 min; P<0.01, n=5). In conclusion, our results suggest that at least three distinct ion transport mechanisms are involved in the RVD in newborn rat cardiomyocytes: (1) K+ and Cl-channels, (2) K(+)-Cl- cotransport, and (3) Na(+)-K(+)-Cl- co-transport.     

Effect of CTRP3 on activation of adventitial fibroblasts induced by TGF-β1 from rat aorta in vitro

CTRP3, discovered as novel adipokines, is a member of the C1q tumor necrosis factor (TNF) related protein (CTRP) super-family. CTRP3 is found to function as adipokines that display diverse biological activities in metabolic and cardiovascular diseases. Recent study demonstrated that CTRP3 was protective against pathological cardiac remodeling in mice. Nevertheless, the effect of CTRP3 on vascular remodeling remains undefined. Our present study aimed to explore the effects of adipokine CTRP3 on the activation of adventitial fibroblasts (AFs) induced by TGF-β1. Immunofluorescent staining, real-time PCR and Western blot were conducted to evaluate the expression of α-smooth muscle-actin (α-SMA) and collagen I. The expression of CTGF was evaluated by enzymelinked immunosorbent assay (ELISA), while the proliferation and migration of adventitial fibroblasts were detected by using cell counting kit-8 (CCK-8) assay and Transwell technique, respectively. Functional analysis showed that CTRP3 inhibited TGF-β1 inducing AFs phenotypic conversion, collagen synthesis, proliferation and migration. The secretion of CTGF was also inhibited by CTRP3. Our findings suggest that CTRP3 may be beneficial to the prevention of cardiovascular diseases and provide a promising therapeutic strategy to attenuate vascular remodeling.     

Involement of glutamate and nitric oxide in the central saltoading—induced cardiovasular responses in conscious rats

Regulation of pericellular proteolytic activity :new cascade by plasmin/plasminogen activator system and metalloproteinase     

What Is the Evidence for Rest,Ice, Compression,and Elevation Therapy in the Treatment of Ankle Sprains in Adults?

Context:

Ankle sprains are common problems in acute medical care. The variation in treatment observed for the acutely injured lateral ankle ligament complex in the first week after the injury suggests a lack of evidence-based management strategies for this problem.

Objective:

To analyze the effectiveness of applying rest, ice, compression, and elevation (RICE) therapy begun within 72 hours after trauma for patients in the initial period after ankle sprain.

Study Selection:

Eligible studies were published original randomized or quasi-randomized controlled trials concerning at least 1 of the 4 subtreatments of RICE therapy in the treatment of acute ankle sprains in adults.

Data Sources:

MEDLINE, Cochrane Clinical Trial Register, CINAHL, and EMBASE. The lists of references of retrieved publications also were checked manually.

Data Extraction:

We extracted relevant data on treatment outcome (pain, swelling, ankle mobility or range of motion, return to sports, return to work, complications, and patient satisfaction) and assessed the quality of included studies. If feasible, the results of comparable studies were pooled using fixed- or random-effects models.

Data Synthesis:

After deduction of the overlaps among the different databases, evaluation of the abstracts, and contact with some authors, 24 potentially eligible trials remained. The full texts of these articles were retrieved and thoroughly assessed as described. This resulted in the inclusion of 11 trials involving 868 patients. The main reason for exclusion was that the authors did not describe a well-defined control group without the intervention of interest.

Conclusions:

Insufficient evidence is available from randomized controlled trials to determine the relative effectiveness of RICE therapy for acute ankle sprains in adults. Treatment decisions must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines.Key Words: ankle ligament injury, cryotherapy, bandages

Key Points

• Randomized controlled trials provide insufficient evidence to determine the effectiveness of rest, ice, compression, and elevation (RICE) therapy for acute ankle sprains in adults.
• Treatment decisions must be made on an individual basis, carefully weighing the relative risks and benefits of each option, and must be based on expert opinions and guidelines.
• Sufficiently powered, high-quality, and appropriately reported randomized trials of the different elements of RICE therapy for acute ankle sprains are needed.

Ankle sprains are one of the most prevalent injuries of the musculoskeletal system. Researchers have estimated that 1 ankle sprain occurs per 10 000 people each day.¹ The most common mechanism of injury is inversion of the plantar-flexed foot. Inversion injuries involve about 25% of all injuries of the musculoskeletal system, which affect more than 20 000 patients in the United States each day.^2,3 About 50% of these injuries are sport related^4,5; some sports (basketball, soccer, and volleyball) have a particularly high incidence of ankle injuries.^6,7 If not treated properly, inversion injuries of the ankle can result in persistent problems in 30% to 40% of patients.^4,8The treatment of inversion ankle injuries is provided by emergency and primary health care physicians, athletic trainers, physiotherapists, and orthopaedic and trauma surgeons. Each year, approximately 1 million patients with acute lateral ankle ligament injuries are examined by primary care physicians in the United States.⁹ The annual cost to society for ankle injuries has been estimated to be approximately €40 million (US $30.4 million) per 1 million people.¹⁰ Most authors use the term sprain to describe a morphologic condition representing a diversity of pathologic conditions, ranging from overstretching of the ligament to complete rupture with gross instability of the joint.¹¹The ankle ligaments are the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL), and together they form the lateral ligament complex of the ankle.¹² The ATFL is the first or only ligament to sustain injury in 97% of the cases.^13,14 Broström⁵ found that combined ruptures of the ATFL and the CFL occurred in 20% of the cases and that isolated rupture of the CFL occurred in only 3%. The PTFL usually is not injured unless a true dislocation of the ankle occurs.⁵ Rest, ice, compression, and elevation (RICE) are generally accepted methods for treating inflammation after trauma, such as acute ankle sprain.^15,16 Inflammation causes pain, edema, hyperalgesia, and erythema, all of which can limit the patient''s ability to perform the rehabilitation required for proper healing.¹⁷ Gentle tension and stretching at the joint promote proper ligament fiber growth into tight, parallel strands. Accumulation of fluid and edema around an injury site also increases tissue damage, delays healing, and can result in some degree of chronic disability.¹⁸According to the Dutch Quality Institute for Healthcare CBO consensus guidelines,¹⁹ RICE therapy is the preferred treatment for the first 4 to 5 days. After this period, the physical examination provides a high-quality assessment.^19–21 The inconsistent outcome of physical examination within 48 hours of trauma is caused by the diffuse character of the pain, the swelling that gives no information about whether it is due to hematoma or edema formation, and the unreliability of the anterior drawer test due to pain and swelling.^19–21Rest, ice, compression, and elevation therapy is an accessible and popular modality in the treatment of acute ankle sprains. Therefore, the objective of our study was to analyze the effectiveness of applying RICE therapy begun within 72 hours after trauma for patients in the initial period of ankle sprain. The specific null hypotheses included the following: (1) No differences existed in outcome measurements between using rest, immobilization, or no movement or mobilization and using early mobilization or movement for acute treatment of ankle sprains; (2) No differences existed in outcome measurements between using ice, cold, cold therapy, cryotherapy, or cooling and using no ice, no cold, or heat for acute treatment of ankle sprains; (3) No differences existed in outcome measurements between using compression and using no compression for acute treatment of ankle sprains; and (4) No differences existed in outcome measurements between using elevation and using no elevation for acute treatment of ankle sprains. In addition to other reviews concerning the treatment of acute lateral ankle sprains^22–28 (also G.M.M.J.K., unpublished data, January 2011), our systematic review will be helpful in the further development of evidence-based treatment recommendations and protocols.     

TNF-α and IL10 polymorphisms interaction increases the risk of ankylosing spondylitis in Chinese Han population

Aims: The target of this article was to reveal the role of tumor necrosis factors α (TNF-α) and Interleukin-10 (IL10) gene polymorphisms in ankylosing spondylitis (AS) development and explore the interaction between these two gene polymorphisms. Methods: The genotyping of gene polymorphims was conducted using ABI Taqman assay method in 84 AS patients and 92 healthy people. Hardy-Weinberg equilibrium (HWE) was checked in the control group and the genotypes and alleles difference were compared with χ² test. Odds ratio (OR) with 95% confidence interval (CI) was calculated to identify the strength of association between gene polymorphism and disease. Meanwhile, multifactor dimensionality reduction (MDR) method was used to analysis the interaction between gene polymorphisms. Results: The genotypes CG+CC of the minor allele in IL10 rs1878672 in cases was obviously higher frequency than the controls (P=0.03) and the minor allele C was also associated with the increased risk of AS, compared with G allele (OR=2.05, 95% CI=1.08-3.89). Rs3024490 in IL10 also showed a significant correlation to the onset risk of AS (GG vs. TT: OR=3.03, 95% CI=1.04-8.87; G vs. T: OR=1.70, 95% CI=1.08-2.68). What’s more, there was the interaction between TNF-α rs3093662 and IL10 rs3021094, rs3024490 polymorphisms in AS. Conclusions: IL10 rs1878672 and rs3024490 polymorphisms obviously increase the susceptibility to AS, but not TNF-α rs3093662. Both IL10 and TNF-α polymorphisms may affect the onset of AS.     

Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoK_ATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoK_ATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoK_ATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.     

HGF suppresses the production of collagen type III and α-SMA induced by TGF-β1 in healing fibroblasts

The aim of this study was to examine the effectiveness of HGF in blocking TGF-beta1-induced collagen III and alpha-smooth muscle actin (alpha-SMA) production in rat healing fibroblasts, fibroblasts were obtained from healing medial collateral ligament (MCL) injury. Cell culture was supplemented with 5 ng/ml of TGF-beta1 along with increasing doses of HGF (10-40 ng/ml). The productions of collagen III in supernatants culture were assayed by enzyme-linked immunosorbent assay. Expression of alpha-SMA was assessed by Western blot. Treatment with TGF-beta1 significantly stimulated collagen III and alpha-SMA production in healing fibroblasts. Remarkably, the addition of HGF reduced productions of all components induced by TGF-beta1 in a dose-dependent manner. This study shows that HGF antagonizes the action of TGF-beta1 effectively in cultured healing MCL injury fibroblasts. The results provide a cellular and molecular basis for HGF's acting as a therapeutic agent for MCL scar formation and poor healing.     

Attenuated "cross talk" between κ-opioid receptors and β-adrenoceptors in the heart of chronically hypoxic rats

At 0.1-1 microM, U50488H, a kappa-opioid receptor agonist, inhibited the stimulatory effects of 1 microM isoprenaline, a beta-adrenoceptor agonist, on the electrically induced intracellular Ca2+ ([Ca2+](i)) transient and cAMP accumulation ("cross talk" between kappa-opioid receptors and beta-adrenoceptors) in the presence of 1 microM ICI118,551, a beta(2)-adrenoceptor antagonist in ventricular myocytes from both normoxic and chronically hypoxic rats. Pretreatment with 20 microg/ml cholera toxin increased the ADP-ribosylation of Gsalpha subunits and the electrically induced [Ca2+](i) transient in both normoxic and chronically hypoxic rats. The effects of cholera toxin were inhibited by 1 microM U50488H and the inhibitory effect of U50488H was attenuated in chronically hypoxic rats. Similarly, 1 microM forskolin also increased the electrically induced [Ca2+](i) transient and cAMP accumulation, which were both inhibited by U50488H, in both normoxic and chronically hypoxic rats. The inhibitory effects of 1 microM U50488H were significantly attenuated in chronically hypoxic rats. The results are novel findings, in that the "cross talk" between kappa-opioid receptors and beta-adrenoceptors is attenuated following chronic hypoxia. The attenuation may be due to decreased responses of Gs-protein and adenylyl cyclase to kappa-opioid receptor activation in addition to desensitization of the receptor itself.     

Assessing the diversity of the virulence potential of Escherichia coli isolated from bacteremia in S?o Paulo, Brazil

Most of the knowledge of the virulence determinants of extraintestinal pathogenic Escherichia coli (ExPEC) comes from studies with human strains causing urinary tract infections and neonatal meningitis and animal strains causing avian colibacillosis. In this research, we analyzed the phylogenetic background, the presence of 20 ExPEC virulence factors, and the intrinsic virulence potential of 74 E. coli strains isolated in São Paulo, Brazil, from 74 hospitalized patients (43 males and 31 females) with unknown-source bacteremia. Unlike other places in the world, the bacteremic strains originated equally from phylogroups B2 (35%) and D (30%). A great variability in the profiles of virulence factors was noted in this survey. Nevertheless, 61% of the strains were classified as ExPEC, meaning that they possessed intrinsic virulent potential. Accordingly, these strains presented high virulence factor scores (average of 8.7), and were positively associated with 12 of 17 virulence factors detected. On the contrary, the non-ExPEC strains, isolated from 39% of the patients, presented a generally low virulence capacity (medium virulence factor score of 3.1), and were positively associated with only the colicin cvaC gene. These results show the importance of discriminating E. coli isolates that possess characteristics of true pathogens from those that may be merely opportunistic in order to better understand the virulence mechanisms involved in extraintestinal E. coli infections. Such knowledge is essential for epidemiological purposes as well as for development of control measures aimed to minimize the incidence of these life-threatening and costly infections.