The liver injury following ischemia and reperfusion is worse in experimental knockout heterozygote mouse model for expression of connexin 43

Abstract Purpose: To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury. Methods: We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology. Results: The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. Conclusions: This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.

Formation of gap junctions between adipose stem cells-derived Schwann cells in a rat model of dyskinesia induced by brain injury / 南方医科大学学报

OBJECTIVE@#To investigate the formation of gap junctions between Schwann cells derived from differentiated adipose stem cells implanted in a rat model of dyskinesia induced by brain injury and its positive effect in promoting functional recovery of the rats.@*METHODS@#In a rat model of hemiplegia induced by motor cortex injury, adipose stem cells or Schwann cells differentiated from adipose stem cells, either with or without RNAi-mediated silencing of Cx43, were transplanted orthotopically in the lesion. The recovery of the motor function of the rats was observed and scored after the transplantation. Rat brain tissues were sampled to detect the expressions of nerve growth factor (NGF) using Western blotting and RT-PCR.@*RESULTS@#All the 3 cell transplantation therapies obviously improved the motor function scores of the rats as compared with the control rats. The expression of NGF in the brain tissue was significantly lower in the control group than in the cell transplantation groups. NGF expression in the brain tissues of rats receiving transplantation of Schwann cells with Cx43 gene silencing was lower than that in rats receiving Schwann cells without Cx43 silencing, and was similar with that in rats transplanted with adipose stem cells. The results of RT-PCR showed that NGF mRNA level in the control group was significantly lower than that in the other 3 groups. NGF mRNA expression was the highest in Schwann cell group without Cx43 silencing, followed by adipose stem cell group, and then by Schwann cell group with Cx43 silencing.@*CONCLUSIONS@#In the rat model of dyskinesia induced by brain injury, transplantations of adipose stem cells and adipose stem cells-derived Schwann cells both promote the functional recovery of brain damage, in which gap junction protein Cx43 plays an important role to promote functional gap junction formation possibly by enhancing NGF expression.

Neuroprotective effects of gap junction blocker octanol on cerebral ischemia-reperfusion injury in rats may be associated with the alleviation of inflammatory response / 国际脑血管病杂志

Objective To investigate the effects of octanol,a gap junction blocker,on the levels of pro-inflammatory cytokines after cerebral ischemia-reperfusion in rats.Methods Seventy-two male SD rats were randomly divided into sham operation group,saline control group,vehicle group,and octanol intervention group (n =18 in each group).The model of transient middle cerebral artery occlusion was induced by the modified suture method.The octanol intervention group was intraperitoneally injected with octanol solution at 5 mmol/kg body weight 30 min before ischemia.The saline control group and the vehicle group were intraperitoneally injected with the same amount of physiological saline and 5％ dimethyl sulfoxide solution 30 min before procedure.The neurological deficit score,brain water content,and cerebral infarction volume in each group were detected after ischemia for 2 h and reperfusion for 24 h.Enzyme-linked immunosorbent assay was used to detect the serum interleukin (IL)-1β,IL-6,and tumor necrosis factor-α (TNF-α) levels.Results Compared with the saline control group and the vehicle group,the neurological deficit score of the octanol intervention group was significantly lower (all P ＜0.05),the brain tissue water content was significantly decreased (P ＜ 0.05),the cerebral infarction volume was significantly reduced (P ＜0.05),and the expression levels of IL-1β,IL-6,and TNF-α were significantly decreased (all P ＜0.05).There were no significant differences in neurological deficit score,brain water content,cerebral infarction volume and serum IL-1 [β,IL-6 and TNF-α levels between the saline control group and the vehicle group.Conclusion Gap junction blocker octanol can reduce cerebral ischemic-reperfusion injury.Its mechanism may be related to the alleviation of inflammatory response.

Roles and mechanisms of connexin 43 in cerebral ischemia-reperfusion / 国际脑血管病杂志

In the central nervous system, gap junctions exist between neurons and glial cells. Among them, connexin 43 (Cx43) is one of the most abundant connexin proteins in the central nervous system,involved in the metabolic coupling of intercellular substance exchange and electrical coupling of electrical signaling. It plays an important role in regulating cell metabolism, homeostasis, and cell differentiation. After cerebral ischemia, the uncoupling of gap junctions and abnormal hemichannel activity cause a steady-state imbalance of the internal and external environment of the cells, eventually leading to brain tissue damage.Therefore, maintaining the normal function of Cx43 is essential for protecting brain tissue from neuronal damage induced by cerebral ischemia-reperfusion.

cAMP transfer across MEGJ mediates regulatory effect of Ang2 on hypo-reactivity after hypoxia in vascular smooth muscle cells / 中国病理生理杂志

AIM:To observe the cyclic adenosine monophosphate(cAMP)transfer across myoendothelial gap junctions(MEGJ)in the regulatory effect of angiopoietin-2(Ang2)on hyporeactivity after hypoxia in vascular smooth mus-cle cells(VSMCs ).METHODS:The double-sided cell co-culture model of vascular endothelial cells(VECs )and VSMCs was set up.The protein expression of inducible nitric oxide synthase(iNOS)was determined by Western blot.The contraction of VSMCs was detected via the leakage of FITC-labeled bovine serum albumin.Alexa Fluor 488-cAMP was used as the tracer to observe the cAMP transfer across MEGJ from VECs to VSMCs.RESULTS:In cultured VECs and VSMCs alone ,the cAMP concentrations were both significantly increased after exogenous Ang 2 treatment and hypoxia ,and more in VECs than that in VSMCs(P<0.05).In the double-sided cell co-culture model,the difference was weakened,and the increase in cAMP concentration in VSMCs after exogenous Ang 2 treatment and hypoxia was antagonized by connexin 43(Cx43)small interfering RNA(siRNA)(P<0.05).Alexa Fluor 488-cAMP in VECs transfered into VSMCs after exoge-nous Ang2 treatment and hypoxia,which was also antagonized by Cx43 siRNA(P<0.05).The cAMP antagonist inhibited the protein expression of iNOS in the VSMCs and the hyporeactivity of the VSMCs after exogenous Ang 2 treatment and hy-poxia(P<0.05).CONCLUSION:Ang2 may regulate the protein expression of iNOS in VSMCs and the hyporeactivity of VSMCs after hypoxia through the cAMP transfer across MEGJ.

Progress in relationship between pannexin and tumors / 中国病理生理杂志

Pannexin is a new member of gap junction families which was discovered in 2000 and was widely distributed in humans. Pannexin forms hemichannels and participates in transmission of small molecules and many other pathophysiological processes. Recent studies have found that the abnormal expression of pannexin is related to occurrence and development of tumors. This article reviews the relationship between pannexin and tumors,and aims to provide new i-deas for treatment of tumors.

Visión celular y molecular de la ortopedia funcional de los maxilares

Actualmente, los mecanismos biológicos que subyacen a la estimulación ortopédica funcional están en proceso de entendimiento; sin embargo, se sabe que el osteocito juega un rol esencial, al recibir y transformar dicho estímulo funcional hacia una señal bioquímica, lo que da como consecuencia la secreción de diversas moléculas. Estas se movilizan entre los osteocitos, gracias a su extensa red de uniones comunicantes, y llegan en última instancia a activar a las células efectoras del tejido óseo: osteoblastos y osteoclastos. El objetivo de la revisión es actualizar y compendiar algunos de los más importantes mecanismos celulares y moleculares subyacentes a la terapia ortopédica funcional de los maxilares.

Currently, the biological mechanisms underlying functional orthopedic stimulation are in process of understanding. However, it is known that osteocyte plays an essential role, to receive and process the functional stimulus to biochemical signals giving as result the secretion of various molecules. Such molecules are mobilized between the osteocytes, thanks to its extensive network of gap junctions, ultimately coming to activate effector cells of bone tissue: osteoblasts and osteoclasts. The aim of the review is to update some of the cellular and molecular mechanisms underlying functional orthopedic therapy of the maxillary.

Research progress in mechanism of Astragali Radix and its active components on endothelial cells and their junction / 中草药

To summarize the research progress in vascular endothelial cells junction as well as mechanism of effective components in Yiqi Chinese medicine Astragali Radix in vascular endothelial cells junction based on referring literature in recent year. Astragalus polysaccharides and Astragalus saponins can protect the integrity of endothelial cells junction by increasing tight junction protein and decreasing endothelial cell adhesion molecule. Its protection takes effect by inhibiting endothelin secretion, increasing NO release, inhibiting apoptosis, and promoting endothelial cells proliferation and migration in angiogenesis in addition, while Astragalus flavonoids inhibits apoptosis to protect the junction of endothelial cells. The multiple-targeted protective effect of Astragali Radix in vascular endothelial cells involved in p38 MAPK/NF-κB, Rho/ROCK, PI3K/Akt, and VEGF/Ang-1 signaling pathways. The current study focused on tight junctions as well as adhesion molecule inhibition of monocyte adhesion to endothelial cells. But its protection of gap junctions has rarely been studied.

Enhanced cell gap junctions promotes the radiosensitivity in triple negative breast cancer cells / 实用肿瘤学杂志

Objectvi e To investigate whether promoting gap junctions may contribute to the radiosensi-tivity in triple negative breast cancer( TNBC)cells.Methods HCC70(triple-negative),MCF-7(ER-posi-tive)or SK-BR3(HER2-positive )cells were transfected with pcDNA/5 -Cx43 expression plasmid using liposome 2000.The transfected cells were treated with various doses of radiation(0,5,10,15 Gy),and the level of Cx43 protein was determined by Western blot and the cell connectivity was determined by fluorescent tracer technique. Cell proliferation inhibition,clone formation ability and apoptosis were detected using MTT,clone formation assay, AnnexinV-FITC/PI double staining and flow cytometer,respectively.Results The level of Cx43 protein signifi-cantly increased in HCC 70 -Cx43 ,MCF-7 -Cx43 and SK-BR3 -Cx43 cells.After transfection the cells were treated with various doses of radiation,level of Cx43protein was gradually enhanced in dose dependent fashion .The re-sults form fluorescent tracer technique showed that fluorescence intensity was gradually elevated with increase of radiation doses.Cell viability and clone formation ability were decreased gradually in dose dependent manner in HCC70-Cx43 ,MCF-7 -Cx43 and SK-BR3-Cx 43 cells.Unexpectedly,the inhibitive effect of proliferation ability and clone formation ability in HCC70 -Cx43 cell was higher than in MCF-7 -Cx43 and SK-BR3 -Cx43 cells under same conditions.The results from AnnexinV-FITC/PI and flow cytometer showed that apoptosis rate was enhanced gradually accompanying with increase of radiation doses.Conclu sion Enhancing the function of cell gap junc-tions promoted radiosensitivity of breast cancer cells,particularly in TNBC cells.Radiation can strengthen cell gap junctions in breast cancer cell and cytotoxicity of TNBC cell can be enhanced by both synergistic effects.

Mechanism of 17β-estrogen on intracellular free calcium regulation in smooth muscle cells at the ;endometrial-myometrial interface in uteri with adenomyosis / 中华妇产科杂志

Objective To investigate the regulation mechanism of estrogen on the free calcium of smooth muscle cells at the endometrial-myometrial interface (EMI) in uteri with adenomyosis. Methods From September 2011 to November 2012, 59 uterine myometrial specimens were obtained from 59 cases underwent hysterectomy, including 28 adenomyosis patients as adenomyosis (ADS) group and 31 patients with cervical intraepithelial neoplasia Ⅲ as control group. EMI smooth muscle cells were cultured and loaded with calcium ion fluorescent probe fluo-4/AM. After treated with trisphosphate (IP3) receptor antagonist, blocker of sarcoplasmic reticulum calcium-adenosine triphosphate (ATP), depleted agent of the ryanodine receptor-operated Ca2+, inhibitor of L-type calcium channel, inhibitor of Na+-Ca2+exchanger, the labeled cells were stimulated with estrogen. The changes of intracellular Ca2+fluorescence intensity were detected by laser scanning microscopy. The changes of intracellular Ca2+concentration was indicated byΔF[Ca2+]i. Results (1) Under normal calcium conditions, after the stimulation of estrogen, intracellular Ca2+fluorescence intensity in ADS group and control group both increased than those without estrogen. TheΔF[Ca2+]i in ADS group was 384±26, and in the control groupΔF[Ca2+]i was 235±20. TheΔF[Ca2+]i in ADS group was higher than that in the control (P0.05). But, the ΔF[Ca2 +]i in ADS group was significantly reduced after treatment compared to before treatment, (211 ± 19 vs 384 ± 28; P=0.001). The increase in control group was almost the same with before (203±16 vs 234±22, P=0.141). (4) After treated with inhibitor of Na+-Ca2+exchanger, theΔF[Ca2+]i in ADS group was 357 ± 24 and in the controlΔF[Ca2+]i was 209±19. The increase in ADS group was significant higher than that in the control (P=0.000). Compared withΔF[Ca2+]i on the condition without treating with inhibitor of Na+-Ca2+exchanger,ΔF[Ca2+]i was 363±21 in ADS group andΔF[Ca2+]i was 237±20 in control group after treatment. When compared with before treatment, there was no significant difference in both groups (P>0.05). Conclusions The increase of intracellular Ca2+induced by estrogen at EMI smooth muscle cells in adenomyosis patients was mostly from the release of arcoplasmic reticulum, and also from the Ca2+influx controlled by L-type calcium channel. The increase of Ca2+inducing abnormal contraction of EMI muscle may have relationship with the development of adenomyosis.

Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo

BACKGROUND: In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions. METHODS: We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system. RESULTS: Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms. CONCLUSION: These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

Anticonvulsant activity of gap-junctional blocker carbenoxolone in albino rats.

Background: Gap junctions (GJs) are clusters of channels that connect the interiors of adjoining neurons and mediate electrical/electrotonic coupling by transfer of ions and small molecules. Electrotonic coupling between principal neurons via GJs is increasingly recognized as one of the mechanisms in the pathogenesis of the abnormal neuronal synchrony that occurs during seizures. Carbenoxolone the succinyl ester of glycyrrhetinic acid obtained from liquorice has been shown to have the property of blocking gap junctional intercellular communication. The objectives were to study if carbenoxolone has in-vivo anticonvulsive activity in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure models and to probe the functional role of GJs in seizures. Methods: Carbenoxolone was tested for anticonvulsive effect in albino rats subjected to seizures by the PTZ and MES at three doses 100 m/kg, 200 m/kg, 300 m/kg. In the PTZ model parameters observed were seizure protection, seizure latency and seizure duration. In the MES model parameters observed were seizure protection and seizure duration. Results: The results showed that the carbenoxolone has anticonvulsant activity in both PTZ and MES induced seizures with better protection in the PTZ induced seizures. In the PTZ model carbenoxolone produced a statistically significant increase in seizure latency, decrease in seizure duration and seizure protection. In the MES model carbenoxolone produced a statistically significant decrease in seizure duration. Conclusions: Carbenoxolone has in-vivo anticonvulsive effect and could be useful in both petitmal (absence) seizures and grand mal (generalized tonic-clonic epilepsy) seizures. The protective effect of carbenoxolone could be due to blockade of GJ channels that mediate electro tonic coupling and thereby prevent the neural synchronization that is characteristic of seizures. The study also supports the view that GJs have a functional role in the electrophysiology of seizures and GJ blockers have potential as a new class of antiepileptic drugs.

Research progress in interactions between neuron and satellite glial cells / 中国药理学通报

Recent studies suggest that glial cells play an impor-tant role in nervous system. Like astrocytes in the central nervous system,satellite glial cells( SGCs) also participate in the physio-logical and pathological processes of the peripheral nervous sys-tem. SGCs affect neuronal functions through neuro-glial interac-tions. In this review,we summarize the current understanding of how SGCs affect the function of neurons.

Abnormal expression of connexin 36 plays a role in the pathogenesis of levodopa induced dyskinesia in rat model of Parkinson' s disease / 中华神经科杂志

Objective To explore whether gap junction disturbances are involved in the pathogenesis of levodopa-induced dyskinesia ( LID ). Methods The hemi-parkinsonian ( PD ) rat was treated intraperitoneally with L-dopa methylester (20 mg/kg) and benserazid (10 mg/kg) for 21 days and abnormal involuntary movement was evaluated to establish LID rat model. The experimental animals were divided into three groups: LID group, PD group and normal control group, respectively. The behavior responses of intraperitoneal injection of different doses of carbenoxolon and intracerebroventricular injection of quinine were observed to estimate the effects of gap junctional blockade on the abnormal involuntary movement ( AIM ) in the rat model of LID. Double immunofluorescence labeling was used to analyze the expression of connexin 36 ( Cx36 ) in enkephalin positive medium spiny neurons and parvalbumin ( PV ) positive interneurons in the striatum. Western blottings was used to observe the expression of Cx36 in the striatum and moter cortex. Results Behavioral characteristics indicated that high dose of carbenoxolone ( >60 mg/kg) intraperitoneal injection and intracerebroventricular injection of quinine ( 0.5, 1.0, 2.0 μmol/L, > 2.5 μmol/L ) could decrease the AIM score of LID rats. Western blotting indicated that expression of Cx36 in lesioned striatum and motor cortex of LID rat model was 219.56% ±18.12% and 226.03% ±16.33%, respectively, which induced a significant upregulation in comparison with the normal control group (104.05% ±3.82%, t=15.389, P<0.01;105.27% ±2.82%,t=8.074, P<0.01) and untreated PD group (119.31% ±8.92%, t=13.356, P<0.01; 138.20% ±17.88%, t=5.872, P<0.01). Double immunofluorescence labeling staining revealed that Cx36 expression was increased in Enk-positive striatum neurons in LID model ( 57.59% ±5.36%) compared with that in normal control group (32.67% ±4.22%) and PD group (37.24% ±0.86%, F=78.060, P<0.01). The expression of Cx36 in PV-positive interneurons was also elevated in LID group (68.49% ±11.60%) in comparison with normal control group ( 40.43% ± 2.30%) and PD group ( 31.92% ± 5.68%, F = 39.567, P < 0.01 ).Conclusions The Cx36 expression is generally increased in lesioned striatum and motor cortex of LID rat model. In the striatum, the up-regulation of Cx36 is specifically observed in Enk-positive striatum neurons and in PV-positive interneurons. The dyskinesia behavior of LID rats can be significantly reduced by treatment with gap junction blockade. All these results suggest that gap junction dysfunction may play an important role in the pathogenesis of LID.

Astrocytic gap junction protein and cerebral ischemia / 国际脑血管病杂志

Studies have shown that gap junction (GJ) of astrocytes plays an important role in ischemic brain injury.Therefore,GJ may become a new target for the treatment of ischemic brain injury.In recent years,although the relationship between GJ of astrocytes and ischemic brain injury has been extensively studied,the conclusions are not consistent.This article reviews the structure,distribution,function of GJ,and its research progress related ischemic brain injury.

Modulation of the respiratory rhythm by gap-junction blockers 18-α-glycyrrhetinic acid and 18-β-glycyrrhetinic acid.

Gap junction proteins are expressed in the pre-Bötzinger complex of the respiratory network but it remains under discussion how they modulate the respiratory rhythm generation. In the present study we tested whether the gap junction blockers 18-β-glycyrrhetinic acid (18-β- GA) and 18-α-glycyrrhetinic acid (18-α-GA) change either the phrenic nerve (PN) discharge frequency or amplitude. The PN discharge was recorded using the working heart-brainstem preparation of adult wistar rats (P22- P28) exposed to increasing concentrations of the gap junction blockers (0.1; 1; 10; 20 μM). With the two lower concentrations (0.1; 1 μM) of 18-β-GA, PN discharge frequency decreased to 46±15% (p=0.007) of the control value while it increased to 173±57% (p=0.16) with the two higher concentrations (10; 20 μM). Surprisingly, with 18-α-GA the PN discharge frequency was not significantly changed with any of the concentrations used. Enhancing the respiratory drive with 12% CO2, the PN discharge frequency increased tendencially with rising concentrations of 18-β-GA, but again no significant change was observed with 18-α-GA. PN-amplitudes were slightly reduced over the course of the experiments, while the frequency of the heartbeat was not significantly changed at any time with any concentration.

Effects of propofol, etomidate and midazolam on gap junction function in rats / 中华麻醉学杂志

Objective To evaluate the effects of propofol,etomidate and midazolam on gap junction function in rats in vitro and in vivo.Methods Experiment Ⅰ NRK52E cells were seeded in 6-well plates with the density of 1.0 × 105/ml and randomly divided into 4 groups (n =6 wells each):control group (group C),propofol group (group P),etomidate group (group E) and midazolam group (group M).In group C,NRK52E cells were cultured in DMEM-F12 culture medium containing 10％ fetal bovine serum.In P,E and M groups,propofol,etomidate and midazolam (with the final concentrations of 15,8 and 4μmol/L,respectively) were added to the culture medium,respectively,and the cells were then incubated for 1 h.Parachute dye-coupling assay was used to measure the gap junction function in NRK52E cells.Experiment Ⅱ Twenty-four male Sprague-Dawley rats,aged 2 months,weighing 220-280 g,were randomly divided into 4 groups (n =6 each):propofol group (group P),etomidate group (group E),midazolam group (group M),and control group (group C).In P,E and M groups,propofol 100 mg/kg,etomidate 6 mg/kg and midazolam 5 mg/kg were injected intraperitoneally once a day for 3 consecutive days,respectively.The equal volume of normal saline was given instead in group C.The animals were sacrificed at 30 min after the last administration and the renal cortex was harvested to measure the gap junction function using tissue scrape and load assay.Results Compared with group C,the gap junction function was significantly decreased in P and E groups (P ＜ 0.05),and no significant change was found in the gap junction function in group M (P ＞ 0.05).Conclusion Propofol and etomidate significantly inhibit the gap junction function in NRK52E cells and renal tissues in rats,but midazolam produces no effect.

Effects of hypothermia combined with sevoflurane on expression of myocardial gap junction protein connexin 43 in isolated rabbit hearts / 中华麻醉学杂志

Objective To investigate the effects of hypothermia combined with sevoflurane on expression of myocardial gap junction protein connexin 43 (Cx43) in isolated rabbit hearts.Methods Healthy adult rabbits of both sexes,weighing 1.5-2.0 kg,were sacrificed after anesthetization.The hearts were rapidly excised and perfused in a langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃ in a langendorff apparatus.Forty isolated hearts were randomly divided into 4 groups (n =10 each):control group (group C),hypothermia group (group H) and hypothermia combined with sevoflurane group (group HS).At 15 min of equilibration,the perfusion with K-H solution was continued at 37 ℃ in group C,K-H solution saturated with 2.4％ sevoflurane was perfused at 37 ℃ in group S,K-H solution was perfused at 30 ℃ in group H,and K-H solution saturated with 2.4％ sevoflurane was perfused at 30 ℃ in group HS.At 30 min of perfusion,myocardial specimens were obtained from the anterior wall of the left ventricle for detection of the expression of Cx43 in myocardial cells (by immunohistochemistry and Western blot).Results Compared with group C,Cx43 expression was downregualted in group H (P ＜ 0.05),and no significant change was found in Cx43 expression in S and HS groups (P ＞ 0.05).Cx43 levels distributed mainly in the intercalated disc in S and HS groups,and in H group the distribution of Cx43 levels in the intercalated disc was less,but the percentages of lateralized Cx43 were increased.Conclusion Sevofurane can inhibit hypothermia-induced down-regulation and distribution disturbance of myocardial Cx43 expression,which may be the mechanism by which sevofurane inhibits hypothermia-induced arrhythmia.

AMPc: una molécula clave en los eventos de regulación inmune y en el control de la replicación del VIH / cAMP: A keymolecule in events of immune regulation and in the control of HIV replication

El monofosfato de adenosina cíclico (AMPc) induce la activación de la proteína cinasa A, la cual regula negativamente la activación, la proliferación celular y la producción de IL-2, en células T. En células infectadas con el virus de inmunodeficiencia humana, el monofosfato de adenosina cíclico suprime la actividad de transcripción del promotor del virus y el paso del ADN viral del citoplasma al núcleo. El incremento del monofosfato de adenosina cíclico mediado por células T reguladoras CD4+, empleando la inyección de esta molécula en células blanco a través de las uniones comunicantes o empleando el eje CD39-CD73 para generar adenosina es utilizado para suprimir otras poblaciones celulares. En esta revisión se propone que la modulación del monofosfato de adenosina cíclico por las células T reguladoras CD4+ podría tener un papel dual durante la evolución de la infección por el virus de inmunodeficiencia humana. Su papel benéfico se centraría principalmente en el control de la replicación viral y factores de transcripción, o evitando la infección de nuevas células blanco por disminución en la expresión de los receptores virales. Paradójicamente, la segunda posibilidad es que el aumento del monofosfato de adenosina cíclico podría tener un papel perjudicial, debido al efecto negativo sobre la proliferación, activación, respuesta citotóxica y en la producción de citocinas que se observa durante la infección viral.

Cyclic adenosine monophosphate induces the activation of protein kinase A, which negatively regulates activation, proliferation and IL-2 production in T cells. In cells infected with human immunodeficiency virus, cyclic adenosine monophosphate suppresses the transcriptional activity of long terminal repeats and the amount of viral DNA from the cytoplasm to the nucleus. The increase in cyclic adenosine monophosphate mediated by CD4+ regulatory T cells, using either the influx of this molecule in target cells through the GAP junctions or by CD39-CD73 to generate adenosine, is used by CD4+ regulatory T cells to suppress other cell populations. In this review, we suggest that modulation of cyclic adenosine monophosphate by CD4+ regulatory T cells may have a dual role during the evolution of human immunodeficiency virus infection. The beneficial role would be mainly focused on the control of viral replication and transcription factors to replicate the virus, and/or preventing the infection of new target cells, decreasing the expression of the viral co-receptors. Paradoxically to this beneficial role, the second possibility is that increased cyclic adenosine monophosphate could have a detrimental role, due to the negative effect on proliferation, activation, cytotoxic response and cytokine production, which occurs during viral infection.

Remodelado estrcctural y de gap junctions en un modelo 3d de aurícula humana / Strctural remodeeling and of gap junctions in a 3d model of human atrial

Introducción: la fibrilación auricular (AF), es la más común de la arritmia cardiaca sostenida y un factor de riesgo para el accidente cerebro vascular y otras morbilidades, si no es tratada. Estudios epidemiológicos muestran que la AF tiende a perpetuarse con el tiempo, generando cambios electrofisiológicos y anatómicos denominados: remodelados auriculares. Se ha demostrado que estos cambios provocan variaciones de la velocidad de conducción (CV), en el tejido auricular. Objetivo: estudiar el efecto del remodelado de gap junctions en la propagación del potencial de acción, implementando un modelo 3D de aurícula humana altamente realista. Materiales y Métodos: se incorporaron los cambios generados por el remodelado eléctrico a un modelo de potencial de acción (AP) de miocito auricular, acoplado con un modelo tridimensional anatómicamente realista de aurícula humana dilatada. Mediante simulaciones de la propagación del AP en condiciones de remodelado eléctrico y anatómico, y de remodelado de gap junctions, se midieron las ventanas vulnerables de generación de reentradas en la base de las venas pulmonares izquierdas de la aurícula. Resultados: los resultados obtenidos indican que la ventana vulnerable en el remodelado de gap junctions, se desplazó 38 ms con relación al modelo dilatado, lo que nos muestra el impacto de la dilatación con remodelado de gap junction. Conclusiones: el remodelado eléctrico generó una disminución del 70 % en la duración del potencial de acción y una disminución de las velocidades de conducción entre un 14.6 y un 26 %, que fueron medidas en diferentes regiones de la aurícula dilatada. El foco disparado en la base de las venas pulmonares izquierdas, generó un frente de onda que mantiene una actividad reentrante debido a la anatomía subyacente de las venas pulmonares.

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a significant risk factor for cerebrovascular accident and other morbidities if left untreated. Epidemiological studies show that AF tends to persist over time, creating electrophysiological and anatomical changes called atrial remodeling. It has been shown that these changes result in variations in conduction velocity (CV) in the atrial tissue. Objective: to study the effect of remodeling of gap junctions in the propagation of the action potential by implementing a highly realistic 3D human atrial model. Materials and methods: the changes caused by electrical remodeling were incorporated in an atrial myocyte action potential (AP) model coupled with an anatomically realistic three-dimensional model of dilated human atria. Through simulations of the AP spread in variations of anatomical and electrical remodeling and of gap junctions remodeling, vulnerable windows of reentry generation were measured at the base of the atrium left pulmonary veins. Results: the results obtained indicate that vulnerable window in the gap junctions remodeling moved 38 ms in relation with the expanded model which shows the impact of the dilatation gap junction remodeling. Conclusions: the electrical remodeling produced 70% decrease in action potential duration and decreased conduction velocities between 14.6 and 26 %, which were measured in different regions of the dilated atrium. The focus shot at the base of the left pulmonary veins created a wave which maintains a reentering activity due to the underlying anatomy of the pulmonary veins.